bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Outcomes between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents with Sentinel Lymph Node Positive Cutaneous Melanoma
Authors: Scoville Steven D. , Stanek Joseph R. , Rinehardt Hannah , Sutthatarn Pattamon , Abdelhafeez Abdelhafeez H. , Talbot Lindsay J. , Malek Marcus , Leraas Harold J. , Tracy Elisabeth T. , Chen Stephanie Y. , Kim Eugene S. , Lotakis Dimitra M. , Ehrlich Peter F. , Favela Juan G. , Le Hau D. , Davidson Jacob , Wilson Claire A. , Seemann Natashia M. , Osman Yasmin , Piche Nelson , Hoang Victoria , Petroze Robin T. , Polites Stephanie F. , McKay Katlyn G. , Correa Hernan , Lovvorn Harold N. , Lee Yu M. , Balagani Akshitha , Dasgupta Roshni , Aldrink Jennifer H. 
Published: July 2023

Objective:
To determine the impact of nodal basin ultrasound surveillance (US) versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma

Summary of Background Data:
Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma.

Methods:
Patients ≤18 years diagnosed with cutaneous melanoma between 2010-2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information.

Results:
Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. 67 total patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 years) than CLND (median age 11.3 years; P=0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P=0.28) or death from disease (2.2% vs 9.7%; P=0.36) for those who underwent US vs CLND, respectively.

Conclusions:
Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.
Improving Surgical Outcomes in Pelvic Exenteration Surgery
Authors: van Kessel Charlotte S. , Waller Jacob , Steffens Daniel , Lee Peter J. , Austin Kirk K.S. , Stalley Paul D. , Solomon Michael J. 
Published: July 2023

Objective:
To assess the effect of changing our sacrectomy approach from prone to anterior on surgical and oncological outcomes.

Background:
In patients with advanced pelvic malignancy involving the sacrum, pelvic exenteration (PE) with en-bloc sacrectomy is the only potential curative option but morbidity is high. Over time sacrectomy techniques have evolved from prone sacrectomy (PS) to abdominolithotomy sacrectomy (ALS,

S3) and high anterior cortical sacrectomy (HACS, >S3) to optimize surgical outcomes.

Methods:
A retrospective, single institution analysis of prospectively collected data for patients undergoing PE with en-bloc sacrectomy between 1994 and 2021 was performed.

Results:
363 patients were identified and divided into PS (n=77, 21.2%), ALS (n=247, 68.0%) and HACS (n=39, 10.7%). Indications were: locally advanced (n=92) or recurrent (n=177) rectal cancer, primary other (n=31), recurrent other (n=60) and benign disease (n=3). PS resulted in longer operating time (P<0.01) and more blood loss (P<0.01). Patients with HACS had more major nerve (87.2%) and vascular (25.6%) resections (P<0.01). VRAM flap repair was less common following HACS (7.7%) than ALS (25.5%) and PS (27.3%) (P=0.040). R0 rate was 80.8%, 65.8% and 76.9% following ALS, PS and HACS, respectively (P=0.024). Wound-related complications and re-operations were significantly reduced following ALS and HACS compared to PS.

Conclusion:
Changing our practice from PS to an anterior approach with ALS or HAS has been safe and improved overall surgical and peri-operative outcomes, while maintaining good oncological outcomes. Given the improved peri-operative and surgical outcomes, it would be important for surgeons to learn and adopt the anterior sacrectomy approaches.
Reactive oxygen species: role in obesity and mitochondrial energy efficiency
Authors: Corkey Barbara E. 
Published: July 2023

Changes correlating with increasing obesity include insulin resistance, hyperlipidaemia, hyperinsulinaemia, highly processed food and environmental toxins including plastics and air pollution. The relationship between the appearance of each of these potential causes and the onset of obesity is unknown. The cause(s) must precede obesity, the consequence, and temporally relate to its rising incidence. Macronutrients such as carbohydrates or fats are unlikely to cause obesity since these have long been constituents of human diets. Furthermore, food consumption and body weight have been well-regulated in most humans and other species until recent times. Thus, attention must focus on changes that have occurred in the last half-century and the relationship between such changes and specific populations that are impacted. The hypothesis presented here is that substances that have entered our bodies recently cause obesity by generating false and misleading information about energy status. We propose that this misinformation is caused by changes in the oxidation–reduction (redox) potential of metabolites that circulate and communicate to organs throughout the body. Examples are provided of food additives that generate reactive oxygen species and impact redox state, thereby, eliciting inappropriate tissue-specific functional changes, including insulin secretion. Reversal requires identification, neutralization, or removal of these compounds.This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Fat-free mass and resting metabolic rate are determinants of energy intake: implications for a theory of appetite control
Authors: Hopkins Mark , Gibbons Catherine , Blundell John 
Published: July 2023

Any explanation of appetite control should contain a description of physiological processes that could contribute a drive to eat alongside those that inhibit eating. However, such an undertaking was largely neglected until 15 years ago when a series of independent research programmes investigated the physiological roles of body composition and appetite. These outcomes demonstrated that fat-free mass (FFM), but not fat mass, was positively associated with objectively measured meal size and energy intake (EI). These findings have been accompanied by demonstrations that resting metabolic rate (RMR) is also positively associated with EI, with the influence of FFM largely mediated by RMR. These findings re-introduce the role of drive into models of appetite control and indicate how this can be integrated with processes of inhibition. The determinants of EI fit into an evolutionary perspective in which the energy demands of high metabolic rate organs and skeletal tissue constitute a need state underlying a tonic drive to eat. This approach should lead to the development of integrated models of appetite that include components of body composition (FFM) and energy expenditure (RMR) as tonic biological signals of appetite alongside other traditional tonic (adipose tissue derived) and episodic signals (gastrointestinal tract derived).
This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Does eating less or exercising more to reduce energy availability produce distinct metabolic responses?
Authors: Halsey Lewis G. , Areta José L. , Koehler Karsten 
Published: July 2023

When less energy is available to consume, people often lose weight, which reduces their overall metabolic rate. Their cellular metabolic rate may also decrease (metabolic adaptation), possibly reflected in physiological and/or endocrinological changes. Reduced energy availability can result from calorie restriction or increased activity energy expenditure, raising the following question that our review explores: do the body's metabolic and physiological responses to this reduction differ or not depending on whether they are induced by dietary restriction or increased activity? First, human studies offer indirect, contentious evidence that the body metabolically adapts to reduced energy availability, both in response to either a calorie intake deficit or increased activity (exercise; without a concomitant increase in food intake). Considering individual aspects of the body's physiology as constituents of whole-body metabolic rate, similar responses to reduced energy availability are observed in terms of reproductive capacity, somatic maintenance and hormone levels. By contrast, tissue phenotypic responses differ, most evidently for skeletal tissue, which is preserved in response to exercise but not calorie restriction. Thus, while in many ways ‘a calorie deficit is a calorie deficit’, certain tissues respond differently depending on the energy deficit intervention.
This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Obesity and environments external to the body
Authors: Ulijaszek Stanley 
Published: July 2023

Studies of environment and obesity usually use epidemiologically tractable measures that are proxies for energy balance or macronutrient composition intake, mostly to identify individual behavioural changes for prevention or reduction of obesity, or inform policy. Of environments external to the body as they relate to obesity, the built environment and the food environment are considered among the most important. Incorporating human sociality into obesity and environments research enriches the field by offering possible ways for understanding obesity production via social stress, dietary preference, food consumption and physical activity. External environments are in flux, however, especially with changing urban form and social environmental hybridity since Web 2.0, with urban polycentricity and networked and online activity influencing obesity production in new ways. While the world's rural populations are experiencing the fastest increases in obesity, large urban populations benefit from scale in setting the physical conditions for physical activity and healthy food availability, with larger and polycentric cities having lower rates of obesity than smaller monocentric or dispersed cities. It is argued that built, food and social environments set the context for obesity production or its amelioration, with sociodemographic factors being more important than new phenomena such as digital and smart technologies.This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
The fructose survival hypothesis for obesity
Authors: Johnson Richard J. , Lanaspa Miguel A. , Sanchez-Lozada L. Gabriela , Tolan Dean , Nakagawa Takahiko , Ishimoto Takuji , Andres-Hernando Ana , Rodriguez-Iturbe Bernardo , Stenvinkel Peter 
Published: July 2023

The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animalsin advanceof crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span.This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Deciphering the interaction surface between the West Nile virus NS3 and NS5 proteins
Authors: Brand Carolin , Geiss Brian , Bisaillon Martin 
Published: July 2023

West Nile virus (WNV) is the most prevalent mosquito-borne disease and the leading cause of viral encephalitis in the continental United States. It belongs to the Flavivirus family which includes other important human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika viruses (ZIKV). Despite several decades of research, no specific antiviral drugs are available to treat Flavivirus infections. The present study characterizes the interaction between the WNV NS3 and NS5 proteins for the purpose of identifying hotspots in the protein-protein interaction which could be targeted for the development of antiviral therapeutics. We previously developed an interaction model in silico based on data available in the literature. Here, potential interacting residues on NS3 and NS5 were mutated in a WNV replicon, and seven mutations in the NS3 protein were found to drastically reduce viral replication. In addition to being well conserved among mosquito-borne Flaviviruses, these residues are located on the protein’s surface in two clusters which might be interesting new targets for future drug development.
Prevalence of and risk factors for peripheral artery disease in rural South Africa: A cross-sectional analysis of the HAALSI cohort
Authors: Beidelman Erika Teresa , Rosenberg Molly , Wade Alisha N. , Crowther Nigel , Kalbaugh Corey A. 
Published: July 2023

AbstractIntroductionThe burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population.MethodsWe used data from 1,883 participants of the HAALSI cohort of South African adults aged 40-69 years with available ankle-brachial index (ABI) measurements. We defined clinical PAD as ABI ≤0.90 or >1.40 and borderline PAD as ABI >0.90 & ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios with log-binomial models.ResultsOverall, 6.6% (95% CI: 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD while 44.7% (95% CI: 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9, 95% CI: 1.2-3.1 for ages 50-59 compared to 40-49; PR: 2.5, 95% CI: 1.5-4.0 for ages 60-69 compared to 40-49) and C-reactive protein (PR: 1.08, 95% CI: 1.03-1.12) were associated with increased prevalence of clinical PAD. All other examined factors were not associated with clinical PAD.ConclusionsWe found high PAD prevalence for younger age groups compared to previous research and a lack of evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.
Invasion of the stigma by the pollen tube or an oomycete pathogen: striking similarities and differences
Authors: Riglet Lucie , Hok Sophie , Kebdani-Minet Naïma , Berre Joëlle Le , Gourgues Mathieu , Rozier Frédérique , Bayle Vincent , Bancel-Vallée Lesli , Allasia Valérie , Keller Harald , Rocha Martine Da , Gaude Thierry , Attard Agnés , Fobis-Loisy Isabelle 
Published: July 2023

AbstractThe epidermis is the first barrier that protects organisms from surrounding stresses. Similar to the hyphae of filamentous pathogens that penetrate and invade the outer tissues of the host, the pollen germinates and grows a tube within epidermal cells of the stigma. Early responses of the epidermal layer are therefore decisive for the outcome of these two-cell interaction processes. Here, we aim at characterizing and comparing how the papillae of the stigma respond to intrusion attempts, either by hypha of the hemibiotrophic oomycete root pathogen,Phytophthora parasiticaor by the pollen tube. We found thatP. parasiticaspores attach to the papillae and hyphae subsequently invade the entire pistil. Using transmission electron microscopy, we examined in detail the invasive growth characteristics ofP. parasiticaand found that the hypha passed through the stigmatic cell wall to grow in contact with the plasma membrane, contrary to the pollen tube that advanced engulfed within the two cell wall layers of the papilla. Further quantitative image analysis revealed that the pathogen and the pollen tube trigger reorganization of the endomembrane system (trans Golgi network, late endosome) and the actin cytoskeleton. Some of these remodeling processes are common to both invaders, while others appear to be more specific showing that the stigmatic cells trigger an appropriate response to the invading structure and somehow can recognize the invader that attempts to penetrate.
Protective role of N-acetylcysteine and Sulodexide on endothelial cells after SARS-CoV-2 infection
Authors: Rajewska-Tabor Justyna , Sosińska-Zawierucha Patrycja , Pyda Malgorzata , Bręborowicz Andrzej 
Published: July 2023

AbstractSevere acute respiratory syndrome coronavirus-2 causes hyperinflammation and activation of coagulation cascade and in the result aggravates endothelial cell dysfunction. N-acetylcysteine and Sulodexide have been found to mitigate endothelial damage. The influence on coronary artery endothelial cells of serum collected after 4+/-1 months from coronavirus infection was studied. The concentrations of serum samples of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 were studied. The cultures with serum of patients after coronavirus infection were incubated with N-acetylocysteine and Sulodexide to estimate their potential protective role. The blood inflammatory parameters were increased in the group of cultures incubated with serum from patients after coronavirus infection. Supplementation of the serum from patients after coronavirus infection with N-acetylcysteine or Sulodexide reduced the synthesis of interleukin 6, von Willebrand Factor. No changes in the synthesis of tissue Plasminogen Activator were observed. N-acetylcysteine reduced the synthesis of Plasminogen Activator Inhibitor-1. N-acetylcysteine and Sulodexide increased the tPA/PAI-1 ratio. N-acetylcysteine may have a role in reducing the myocardial injury occurring in the post-COVID-19 syndrome. Sulodexide can also play a protective role in post-COVID-19 patients.
Improving Gonorrhoea Molecular Diagnostics: Genome Mining-Based Identification of Identical Multi-Repeat Sequences (IMRS) inNeisseria gonorrhoeaeGenome
Authors: Shiluli Clement , Kamath Shwetha , Kanoi Bernard N. , Kimani Rachael , Maina Michael , Waweru Harrison , Kamita Moses , Ndirangu Ibrahim , Abkallo Hussein M. , Oduor Bernard , Pamme Nicole , Dupaty Joshua , Klapperich Catherine M. , Lolabattu Srinivasa Raju , Gitaka Jesse 
Published: July 2023

ABSTRACTPurposeCurable sexually transmitted infections (STIs) such asNeisseria gonorrhoeae(N. gonorrhoeae) is a major cause of poor pregnancy outcome. The infection is often asymptomatic in pregnant women and a syndrome-based approach of testing leads to missed diagnosis. Culture followed by microscopy is inadequate and time-consuming. The gold standard Nucleic Acid Amplification Tests (NAATs) require advanced infrastructure settings whilst point of care tests are limited to immunoassays with sensitivities and specificities insufficient to accurately diagnose asymptomatic cases. This necessitates the development and validation of assays that are fit for purpose.Materials and methodsHere, we have identified new diagnostic target biomarker regions forN. gonorrhoeaeusing an algorithm for genome mining of identical multi repeat sequences (IMRS). These were then developed as DNA amplification primers to design better diagnostic assays. To test the primer pair, genomic DNA was 10-fold serially diluted (100pg/μL to 1×10-3pg/μL) and used as DNA template for PCR reactions. The gold standard PCR using 16S rRNA primers was also run as a comparative test, and both assay products resolved on 1% agarose gel.ResultsOur newly developedN. gonorrhoeaeIMRS-PCR assay had an analytical sensitivity of 6 fg/μL representing better sensitivity compared to the 16S rRNA PCR assay with analytical sensitivity of 4.3096 pg/μL. The assay was also successfully validated with clinical urethral swab samples. We further advanced this technique by developing an iso-thermal IMRS, which was both reliable and sensitive for detecting culturedN. gonorrhoeaeisolates at a concentration of 38 ng/μL. Combining the iso-thermal IMRS with a low-cost Lateral Flow Assay, we were able to detectN. gonorrhoeaeamplicons at a starting concentration of 100 pg/μL.ConclusionTherefore, there is a potential to implement this concept within miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for highly reliable point-of-care testing.
Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain
Authors: Di Fraia Domenico , Marino Antonio , Lee Jae Ho , Kelmer Sacramento Erika , Baumgart Mario , Bagnoli Sara , Tomaz da Silva Pedro , Kumar Sahu Amit , Siano Giacomo , Tiessen Max , Terzibasi-Tozzini Eva , Gagneur Julien , Frydman Judith , Cellerino Alessandro , Ori Alessandro 
Published: July 2023

ABSTRACTAging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain’s biology – the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.One-Sentence SummaryTranslation pausing reshapes the aging brain proteome, revealing vulnerabilities in the biogenesis of nucleic-acid protein.