bluuebunny/crossref_metadata_2025_split huggingface dataset:
What are the differences between the three most used classifications for acute colonic diverticulitis? A comparative multicenter study
Authors: Cremonini Camilla , Biloslavo Alan , Robustelli Virna , Giannessi Sandro , Rossi Del Monte Simone , Mastronardi Manuela , Musetti Serena , Strambi Silvia , Coccolini Federico , Chiarugi Massimo , Tartaglia Dario 
Published: September 2023

ABSTRACT

BACKGROUND
Acute left-sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. Currently, the most popular classifications, based on radiological findings, are the modified Hinchey, AAST, and WSES classifications. We hypothesize that all classifications are equivalent in predicting outcomes.

METHODS
This is a retrospective study of 597 patients from four medical centers between 2014 and 2021. Based on clinical, radiological, and intraoperative findings, patients were graded according to the three classifications. Regression analysis and receiver operating characteristic curve analysis were used to compare six outcomes: need for intervention, complications, major complications (Clavien–Dindo >2), reintervention, hospital length of stay, and mortality.

RESULTS
A total of 597 patients were included. Need for intervention, morbidity, and reintervention rates significantly increased with increasing AAST, modified Hinchey, and WSES grades. The area under the curve (AUC) for the need for intervention was 0.84 for AAST and 0.81 for modified Hinchey (p = 0.039). The AUC for major complications was 0.75 for modified Hinchey and 0.70 for WSES (p = 0.009). No differences were found between the three classifications when comparing AUCs for mortality, complications, and reintervention rates.

CONCLUSION
The AAST, WSES, and modified Hinchey classifications are similar in predicting complications, reintervention, and mortality rates. AAST and modified Hinchey scores result the most adequate for predicting the need for surgery and the occurrence of major complications.

Level of Evidence
Prognostic and epidemiological study, level III.
Myopathy and Ophthalmologic Abnormalities in Association With Multiple Skeletal Muscle Mitochondrial DNA Deletions
Authors: Carey Andrew R. , Miller Neil R. , Cui Hong , Allis Katrina , Balog Amanda , Bai Renkui , Vernon Hilary J. 
Published: September 2023

Background:
Establishing a molecular diagnosis of mitochondrial diseases due to pathogenic mitochondrial DNA (mtDNA) variants can be difficult because of varying levels of tissue heteroplasmy, and identifying these variants is important for clinical management. Here, we present clinical and molecular findings in 8 adult patients with classical features of mitochondrial ophthalmologic and/or muscle disease and multiple mtDNA deletions isolated to muscle.

Methods:
The patients were identified via a retrospective review of patients seen in both a tertiary ophthalmology center and a genetics clinic with a clinical diagnosis of chronic progressive external ophthalmoplegia, optic nerve abnormalities, and/or mitochondrial myopathy. Age at onset of symptoms ranged from 18 to 61 years. Ocular manifestations included bilateral optic neuropathy in one patient, bilateral optic disc cupping without optic neuropathy in 2 patients, ptosis in 4 patients, and ocular motility deficits in 2 patients. Five patients had generalized weakness.

Results:
Pathogenic variants in mtDNA were not found in the blood or buccal sample from any patient, but 7 of 8 patients had multiple mtDNA deletions identified in muscle tissue. One patient had a single mtDNA deletion identified in the muscle. Heteroplasmy was less than 15% for all of the identified deletions, with the exception of one deletion that had a heteroplasmy of 50%–60%. None of the patients were found to have a nuclear gene variant known to be associated with mitochondrial DNA maintenance.

Conclusions:
mtDNA deletions were identified in adult patients with ophthalmologic and/or musle abnormalities and may underlie their clinical presentations.
Obesity and thinness: insights from genetics
Authors: Farooqi Sadaf 
Published: September 2023

Genetic disruption of key molecular components of the hypothalamic leptin–melanocortin pathway causes severe obesity in mice and humans. Physiological studies in people who carry these mutations have shown that the adipose tissue-derived hormone leptin primarily acts to defend against starvation. A lack of leptin causes an intense drive to eat and increases the rewarding properties of food, demonstrating that human appetite has a strong biological basis. Genetic studies in clinical- and population-based cohorts of people with obesity or thinness continue to provide new insights into the physiological mechanisms involved in weight regulation and identify molecular targets for weight loss therapy.
This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Diet composition and energy intake in humans
Authors: James Stubbs R. , Horgan Graham , Robinson Eric , Hopkins Mark , Dakin Clarissa , Finlayson Graham 
Published: September 2023

Absolute energy from fats and carbohydrates and the proportion of carbohydrates in the food supply have increased over 50 years. Dietary energy density (ED) is primarily decreased by the water and increased by the fat content of foods. Protein, carbohydrates and fat exert different effects on satiety or energy intake (EI) in the order protein > carbohydrates > fat. When the ED of different foods is equalized the differences between fat and carbohydrates are modest. Covertly increasing dietary ED with fat, carbohydrate or mixed macronutrients elevates EI, producing weight gain and vice versa. In more naturalistic situations where learning cues are intact, there appears to be greater compensation for the different ED of foods. There is considerable individual variability in response. Macronutrient-specific negative feedback models of EI regulation have limited capacity to explain how availability of cheap, highly palatable, readily assimilated, energy-dense foods lead to obesity in modern environments. Neuropsychological constructs including food reward (liking, wanting and learning), reactive and reflective decision making, in the context of asymmetric energy balance regulation, give more comprehensive explanations of how environmental superabundance of foods containing mixtures of readily assimilated fats and carbohydrates and caloric beverages elevate EI through combined hedonic, affective, cognitive and physiological mechanisms.This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping
Authors: Colotte Marthe , Luis Aurélie , Coudy Delphine , Tuffet Sophie , Robene Isabelle , Fenelon Babbitha , Jouen Emmanuel , Leveque Nicolas , Deroche Luc , Alain Sophie , Plumelle Dorian , Tumiotto Camille , Busson Laurent , Lafon Marie-Edith , Bonnet Jacques 
Published: September 2023

AbstractThe Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate positive controls. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage, costly shipping, and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. Here, RNA controls produced by Twist were encapsulated (RNAshells) and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and 6 different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by accelerated aging. The results for a 10-year equivalent storage time at 25 °C were not significantly different from those for unaged samples. This room temperature RNA stability allows the preparation and distribution of large strategic batches which can be stored for a long time and used for standardization processes between detection sites. Moreover, it makes it also possible to use these controls for single use and in the field where large temperature differences can occur. Consequently, this type of encapsulated RNA controls, processed at room temperature, can be used as reference materials for the SARS-Cov-2 virus as well as for other pathogens detection.
TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer
Authors: Cokelaere Célie , Dok Rüveyda , Cortesi Emanuela E. , Zhao Peihua , Sablina Anna , Nuyts Sandra , Derua Rita , Janssens Veerle 
Published: September 2023

AbstractTIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 – all pleiotropic modulators of the DNA Damage Response (DDR). Here, we describe a new role for TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC). TIPRL1 expression was found increased in tumor versus non- tumor tissue, with high tumoral TIPRL1 expression associating with lower locoregional control and decreased survival of RT-treated patients. TIPRL1 deletion in HNSCC cells resulted in increased RT sensitivity, a faster but prolonged cell cycle arrest, increased micronuclei formation and an altered proteome-wide DDR. Upon irradiation, ATM phosphorylates TIPRL1 at Ser265, contributing to TIPRL1-mediated RT resistance. Mass spectrometry analysis identified DNA-PKcs, RAD51 and nucleosomal histones as novel TIPRL1 interactors. Histone binding, although stimulated by RT, was adversely affected by TIPRL1 Ser265 phosphorylation. Our findings underscore a clinically relevant role for TIPRL1 and its ATM-dependent phosphorylation in RT resistance through modulation of DNA damage checkpoint activation and repair.
Exploring The Role Of Isolation By Distance, Isolation By Environment, And Hybridization InCampylorhynchusWrens Along A Precipitation Gradient In Western Ecuador
Authors: Montalvo Luis Daniel , Kimball Rebecca T. , Austin James , Robinson Scott 
Published: September 2023

ABSTRACTClimate variability can cause genetic and phenotypic diversity within species, which affects the evolution of biodiversity. A balance between gene flow and selection maintains changes in the frequency of genetic and phenotypic variants along an environmental gradient. In this study, we investigated a hybrid zone in western Ecuador involving two species of wrens (Aves: Troglodytidae), Campylorhynchus zonatus and C. fasciatus, and their admixed populations. We hypothesized that isolation by distance (IBD) and different ecological preferences, isolation by environment (IBE), result in limited dispersal between populations along the precipitation gradient in western Ecuador.We asked two main questions: (1) What is the relative contribution of IBD and IBE to patterns of genetic differentiation of these species along the environmental gradient in western Ecuador? And (2) Is there evidence of genetic admixture and introgression between these taxa in western Ecuador? We analyzed 4,409 SNPs from the blood of 112 individuals sequenced using ddRadSeq. The most likely clusters ranged from K=2-4, corresponding to categories defined by geographic origins, known phylogenetics, and physical or ecological constraints. Evidence for IBD was strong across all models, and evidence for IBE was less strong but still significant for annual mean precipitation and precipitation seasonality. We observed gradual changes in genetic admixture between C. f. pallescens and C. zonatus along the environmental gradient. Genetic differentiation of the two populations of C. f. pallescens could be driven by a previously undescribed potential physical barrier near the center of western Ecuador. Lowland habitats in this region may be limited due to the proximity of the Andes to the coastline, limiting dispersal and gene flow, particularly among dry-habitat specialists. We do not propose taxonomic changes, but the admixture observed in C. f. pallescens suggests that this described subspecies could be a hybrid between C. z. brevirostris and C. fasciatus, with different degrees of admixture along western Ecuador and northwestern Peru. This study contributes to the knowledge of avian population genomics in the tropics.
The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability
Authors: Ravn-Boess Niklas , Roy Nainita , Hattori Takamitsu , Bready Devin , Donaldson Hayley , Lawson Christopher , Lapierre Cathryn , Korman Aryeh , Rodrick Tori , Liu Enze , Frenster Joshua D. , Stephan Gabriele , Wilcox Jordan , Corrado Alexis D. , Cai Julia , Ronnen Rebecca , Wang Shuai , Haddock Sara , Sabio Ortiz Jonathan , Mishkit Orin , Khodadadi-Jamayran Alireza , Tsirigos Aris , Fenyö David , Zagzag David , Perna Fabiana , Jones Drew R. , Possemato Richard , Koide Akiko , Koide Shohei , Park Christopher Y. , Placantonakis Dimitris G. 
Published: September 2023

SUMMARYGlioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and itsde novoexpression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGC)in vitroandin vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of β-arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of PDGCs with an anti-CD97 antibody-drug conjugatein vitroselectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it for therapeutic purposes.
Plasticity in plant populations may be constrained by performance costs, complex environments and weakly integrated phenotypes
Authors: Hennion Françoise , Labarrere Bastien , Renaudon Marine , Prinzing Andreas 
Published: September 2023

AbstractBackground and AimsOne response of plants to climate warming is plasticity of traits, but plasticity might come at a cost and might be limited by the integration among traits or by simultaneous shift of another environmental condition such as shading. Empirical studies treating simultaneously such costs and limitations of plasticity across populations or maternal lineages within species, and how they depend on the environmental context remain few.MethodsWe studied three plant species from the sub-Antarctic, a region currently facing one of the fastest warming worldwide. For multiple populations or maternal lineages we identified (i) plasticity by exposing seeds from a given source population to different temperature and light treatments, (ii) performance (photosynthesis or morphological performance) and (iii) morphological integration of traits in young plants.Key ResultsWe found that plants from more plastic source populations performed poorly. Plants from more integrated source populations were more plastic. Exposure to shade rendered plants less plastic to a warming trend. Moreover, simultaneous shading and warming, rather thansoleshading orsolewarming, reduced plant performance.ConclusionsOur results suggest that phenotypic integration of intraspecific lineages surprisingly might favour rather than limit plasticity. However, our results also suggest that plasticity in response to climate warming may be limited by parallel increase in shading from other plants including competitors, and itself does not ensure success due to induced performance costs.
Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study
Authors: Williams John A. , Russ Dominic , Bravo-Merodio Laura , Gkoutos Georgios , Bellgrove Mark A. , Bagshaw Andrew P. , Chechlacz Magdalena 
Published: September 2023

AbstractChronotype impacts numerous physiological and disease traits, from metabolic syndrome to schizophrenia. The suprachiasmatic nucleus (SCN) maintains transcriptional-translational feedback loop (TTFL) which acts as a central chronobiological pacemaker, regulating 24-hour cycles throughout the human body. However, each tissue maintains its own peripheral clock, and both endogenous hormones and neurotransmitters and exogenous environmental cues regulate the SCN’s central clock. The extent to which brain regions outside the SCN influence the core TTFL is unknown. Here, we investigated how genetic variability affecting brain regions outside the SCN may indirectly influence chronotype, using Mendelian randomization and causal inference. We performed genome wide association studies (GWAS) based on image derived phenotypes (IDPs) from neuroimaging data (grey matter volume, thickness and surface area, microstructural white matter measures; 42,062 participants), and additionally for sleep duration and morning/evening chronotype (361,739 participants). Significant, single nucleotide polymorphisms (SNPs) associating with each phenotype were entered into 2-sample Mendelian randomization performed using inverse-variance weighted methods (exposure versus outcome): 1) chronotype versus each IDP, 2) sleep versus each IDP and 3) each IDP versus chronotype. Subsequently, we investigated genes where significant instrumental SNPs were located for circadian periodic cycling, interaction with TTFL genes in common biological pathways (genetic, physical, or functional interaction), and enrichment of traits from UK Biobank and GWAS Catalogs. We found three associations with chronotype (morning/evening diurnal preference) outside the SCN based on genetically predicted (FAM76B, DENND1A, CDH11) regional differences in brain volume. Specifically, genetically predicted lower inferior temporal gyrus volume linked to morning phenotype, while lower volume of the superior parietal lobule and angular gyrus linked to evening preference. In addition, evening chronotype exposure influenced superior temporal gyrus volume, and both increased sleep duration and evening chronotype influenced thalamic volume. We conclude that genetically mediated associations between chronotype and brain regions outside SCN exist suggesting novel zeitgeber mechanisms.
Changes in the Dopaminergic circuitry and Adult Neurogenesis linked to Reinforcement Learning in Corvids
Authors: Parishar Pooja , Rajagopalan Madhumita , Iyengar Soumya 
Published: September 2023

AbstractThe caudolateral nidopallium (NCL, an analogue of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in crows, whereas the involvement of other brain regions in these phenomena are unknown. However, recent studies on pigeons have demonstrated that besides NCL, basal ganglia-thalamocortical loops connected to this region play are also crucial for learning. The present study demonstrates that besides NCL, other parts of the caudal nidopallium (NC), avian basal ganglia, and intriguingly, vocal control regions in house crows (Corvus splendens), are involved in visual discrimination. We have also found that training on the visual discrimination task can be correlated to neurite pruning in mature dopaminoceptive neurons and immature doublecortin-positive neurons in the NC of house crows. Furthermore, there is an increase in the incorporation of new neurons throughout NC and the medial striatum which can also be linked to learning. For the first time, our results demonstrate that a combination of structural changes in mature and immature neurons and adult neurogenesis are linked to learning in corvids.
Rewiring of the TCR signalosome in natural intestinal Intraepithelial T lymphocytes drives non-deletional tolerance
Authors: Watt Harriet J. , Chawla Amanpreet Singh , Lamoliatte Frederic , Pryde Sara , Knatko Elena , Rasmussen Kasper D. , Bending David , Swamy Mahima 
Published: September 2023

AbstractIntraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic T cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural T-IEL are agonistically selected in the thymus on self-antigens before migrating directly to the small intestine. Despite having self-reactive T cell antigen receptors (TCR), natural T-IEL are maintained in a tolerized state in the gut by unknown mechanisms. We therefore investigated TCR signaling in T-IEL using multiplexed fluorescent cell barcoding, phosphoproteomics and TCR signaling reporter mouse models, which revealed that TCR signaling is intrinsically suppressed in natural, but not induced, T-IEL. Unexpectedly, we discover that this cell intrinsic suppression was mediated through altered TCR signalosome components. Specifically, downregulation of the key signaling adaptor, Linker for activation of T cells (LAT) during thymic selection is a vital checkpoint for the development and tolerization of natural IELs. Thus, TCR signaling is rewired in self-reactive natural T-IEL to promote tolerance and prevent inappropriate inflammation in the gut.One sentence summarySelf-reactive natural intestinal intraepithelial T lymphocytes are developmentally tolerized by rewiring the T cell antigen receptor signaling pathway through the downregulation of the adaptor protein, LAT.