bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Clinical Measurements to Predict Breast Skin Necrosis
Authors: Lu Wang Marcos , Valenti Alyssa B. , Qin Nancy , Vernice Nicholas A. , Huang Hao , Cohen Leslie E. , Otterburn David M. 
Published: January 2023

Background
Breast skin necrosis can lead to poor healing, reoperation, and unaesthetic reconstructive outcomes after mastectomy. Furthermore, the prolonged recovery can delay adjuvant oncologic regimens. This study aims to explore the role of breast surface area as a risk factor for mastectomy skin flap necrosis and to identify predictive clinical measurements.

Methods
The authors retrospectively identified patients who underwent immediate breast reconstruction (N = 926 breasts) by 2 surgeons at a single institution between 2011 and 2021. Preoperative breast measurements such as nipple-notch (NN) distance, nipple-inframammary fold (NF) distance, chest width (CW), breast circumference (BC), and breast height (BH) were used to estimate breast surface area. Univariate analysis and receiver operating characteristic curves were used to determine predictive measurements and optimal cutoff values.

Results
When approximated using either a cone without base or a half ellipsoid, larger surface area was a significant risk factor for mastectomy skin flap necrosis (P = 0.027 and P = 0.022, respectively). Larger NN, NF, CW, BC, and BH measurements were significant predictors of necrosis (P < 0.05). Surface area (cone without base) greater than 212 cm2, surface area (half ellipsoid) greater than 308 cm2, NN distance greater than 27 cm, NF greater than 8.5 cm, CW greater than 15 cm, BC greater than 29 cm, and BH greater than 10.5 cm are all values shown to increase the incidence of necrosis.

Conclusions
Larger breast surface area is an independent risk factor for breast skin necrosis. Preoperative breast measurements can be a useful adjunct for predicting necrosis in postmastectomy patients.
Patient-Reported Outcomes After Autologous Fat Grafting in Prosthetic Breast Reconstruction
Authors: Sowa Yoshihiro , Inafuku Naoki , Tsuge Itaru , Yamanaka Hiroki , Morimoto Naoki 
Published: January 2023

Introduction
There is widespread recognition of the importance of assessment of patient satisfaction and well-being after breast reconstruction. However, few studies of fat grafting performed simultaneously with implant-based breast reconstruction (IBBR) have accounted for confounding factors, such as patient background and information bias. The aim of this study was to examine patient satisfaction and well-being using multivariate analysis of BREAST-Q scores in patients treated with IBBR combined with fat grafting.

Methods
Seventy-one consecutive patients who underwent IBBR with silicone breast implants were enrolled for a prospective cohort study. Among these patients, 56 responded to the BREAST-Q questionnaire, including 24 who underwent fat grafting at the same time as IBBR (FAT+ group) and 32 who underwent IBBR alone (FAT− group). The BREAST-Q questionnaire was completed 1 year after surgery. Statistical analysis was performed using descriptive and summary statistics to identify differences between the 2 groups.

Results
Logistic regression analysis showed that the FAT+ group was significantly more likely than the FAT− group to have satisfaction with breasts (P = 0.0201) and satisfaction with outcome (P = 0.0364).

Conclusions
Multivariate analysis with consideration of confounding factors indicated that addition of fat grafting to IBBR improves outcomes of breast reconstruction. These results suggest that a minor surgical procedure of fat grafting can improve patient satisfaction and outcomes after breast reconstruction.
The Transfer of Expanded Forehead Superthin Flap Without Frontalis and Less Hair Follicles Pedicled by Superficial Temporal Vessels
Authors: Cao Zilong , Liu Liqiang , Jiao Hu , Fan Jincai , Gan Cheng , Zhang Tiran 
Published: January 2023

Background
The expanded forehead flap pedicled with superficial temporal vessel(s) is a common method to treat facial scar deformity. However, local bulkiness and hair retention have limited the use of this flap.

Methods
Five cadavers were used for anatomy to confirm the forehead “safety zone.” A retrospective study was performed on 15 patients with facial scar deformity who were undergoing the expanded forehead superthin flap (without the expanded capsule, frontalis muscle, and with less hair follicles) pedicled with superficial temporal vessel(s) to transfer and repair the deformity.

Results
Through cadaver anatomy, the range where the subdermal vascular network laid superficial to the hair follicle level was named the “safety zone,” whose average distance between the bilateral penetrating points was 10.2 cm (8.7–11.6 cm). Fifteen patients with facial scar deformity were treated with the superthin flap technique. The trimming size of the safety zone flap was (6–10) × (12–20) cm. The median time of thinning the safety zone was 35 minutes (range, 25–40 minutes). All flaps healed well. The median residual ratio of the hair follicle was 39.8% (29.9%–50.5%). All patients were satisfied with the contour of the flap.

Conclusion
We firstly proposed a concept of forehead safety zone and used the superthin flap without the frontalis muscle and less hair follicles to treat facial scar deformity, and obtained an improved therapeutic effect. We think this is an appealing technique that can manifest facial concave and convex in the fine part, improve compliance of the flap, and reduce the times of laser hair removal.
NUCLEOLIN PROTECTS CARDIOMYOCYTES BY UPREGULATING PGC-1α AND PROMOTING MITOCHONDRIAL BIOGENESIS IN LPS-INDUCED MYOCARDIAL INJURY
Authors: Yin Leijing , Tang Yuting , Luo Zhengyang , Yuan Ludong , Lin Xiaofang , Wang Shuxin , Liang Pengfei , Jiang Bimei 
Published: January 2023

ABSTRACT

Background: Lipopolysaccride-induced myocardial injury was characterized by frequent mitochondrial dysfunction. Our previous studies found that nucleolin (NCL) played important protective roles in myocardial ischemia–reperfusion injury. Recently, it has been found that NCL has a protective effect on LPS-induced myocardial injury in vivo. However, the exact underlying mechanisms that how NCL protects myocardium against the LPS-induced myocardial injury remains unclear. Objective: The aim of the study is to investigate the protective role of NCL in LPS-induced myocardial injury from the aspect of mitochondrial biogenesis. Methods: The cardiac-specific NCL-knockout (NCL−/−) or NCLf/f mice were injected with LPS (10 mg/kg) to induce LPS-induced myocardial injury. The supernatant generated after LPS stimulation of macrophages was used as the conditioned medium to stimulate H9C2 and established the injured cell model. Analysis of mRNA stability, RNA-binding protein immunoprecipitation assay, and luciferase reporter assay were performed to detect the mechanism by which NCL regulated the expression of PGC-1α. Results: The expression of NCL and PGC-1α was elevated in cardiac tissue and cardiomyocytes during LPS-induced myocardial injury. The cardiac-specific NCL-knockout decreased PGC-1α expression, inhibited mitochondrial biogenesis, and increased cardiomyocytes death during LPS-induced myocardial injury in vitro and in vivo. In contrast, the overexpression of NCL could improve mitochondrial biogenesis in H9C2 cells. Moreover, the analysis of mRNA stability and luciferase reporter assay revealed that the interaction between NCL and PGC-1α significantly promoted the stability of PGC-1α mRNA, thereby upregulating the expression of PGC-1α and exerting a cardioprotective effect. In addition, the activation of PGC-1α diminished the detrimental effects of NCL knockdown on mitochondrial biogenesis in vitro and in vivo. Conclusions: Nucleolin upregulated the gene expression of PGC-1α by directly binding to the 5′-UTR of PGC-1α mRNA and increasing its mRNA stabilities, then promoted mitochondrial biogenesis, and played protective effect on cardiomyocytes during LPS-induced myocardial injury. Taken together, all these data showed that NCL activated PGC-1α to rescue cardiomyocytes from LPS-induced myocardial injury insult, suggesting that the cardioprotective role of NCL might be a promising prospect for clinical treatment of patients with endotoxemia.
ARTERIAL DIAMETER VARIATIONS AS A NEW INDEX FOR STROKE VOLUME ASSESSMENT: AN EXPERIMENTAL STUDY ON A CONTROLLED HEMORRHAGIC SHOCK MODEL IN PIGLETS
Authors: Ajavon Florian , Coisy Fabien , Grau-Mercier Laura , Fontaine Jules , Perez Martin Antonia , Claret Pierre-Géraud , Bobbia Xavier 
Published: January 2023

ABSTRACT

Background: The assessment of cardiac output (CO) is a major challenge during shock. The criterion standard for CO evaluation is transpulmonary thermodilution, which is an invasive technique. Speckle tracking is an automatized method of analyzing tissue motion using echography. This tool can be used to monitor pulsed arterial diameter variations with low interobserver variability. An experimental model of controlled hemorrhagic shock allows for multiple CO variations. The main aim of this study is to show the correlation between the femoral arterial diameter variations (fADVs) and the stroke volume (SV) measured by thermodilution during hemorrhagic shock management and the resuscitation of anesthetized piglets. The secondary objective is to explore the respective correlations between SV and subaortic time-velocity index, abdominal aorta ADV, carotid ADV, and subclavian ADV. Methods: Piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes before randomizing the piglets to three resuscitation groups—the fluid-filling group (reanimated with saline solution only), NEph group (norepinephrine + saline solution), and Eph group (epinephrin + saline solution). Speckle tracking, echocardiographic, and hemodynamic measures were performed at different stages of the protocol. Results: Thirteen piglets were recruited and included for statistical analysis. Of all the piglets, 164 fADV measures were attempted and 160 were successful (98%). The correlation coefficient between fADV and SV was 0.71 (95% confidence interval [CI], 0.62 to 0.78; P < 0.01). The correlation coefficient between SV and abdominal aorta ADV, subclavian ADV, and carotid ADV was 0.30 (95% CI, 0.13 to 0.46; P < 0.01), 0.56 (95% CI, 0.45 to 0.66, P < 0.01), and 0.15 (95% CI, −0.01 to 0.30, P = 0.06), respectively. Conclusions: In this hemorrhagic shock model using piglets, fADV was strongly correlated with SV.
MCB-613 exploits a collateral sensitivity in drug resistantEGFR-mutant non-small cell lung cancer through covalent inhibition of KEAP1
Authors: Bassil Christopher F. , Anderson Gray R. , Mayro Benjamin , Askin Kayleigh N. , Winter Peter S. , Gruber Samuel , Hall Tierney M. , Hoj Jacob P. , Cerda-Smith Christian , Hutchinson Haley M. , Killarney Shane T. , Singleton Katherine R. , Qin Li , Jubien-Girard Kévin , Favreau Cécile , Martin Anthony R. , Robert Guillaume , Benhida Rachid , Auberger Patrick , Pendergast Ann Marie , Lonard David M. , Puissant Alexandre , Wood Kris C. 
Published: January 2023

ABSTRACTTargeted therapies have revolutionized cancer chemotherapy. Unfortunately, most patients develop multifocal resistance to these drugs within a matter of months. Here, we used a high-throughput phenotypic small molecule screen to identify MCB-613 as a compound that selectively targetsEGFR-mutant, EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) cells harboring diverse resistance mechanisms. Subsequent proteomic and functional genomic screens involving MCB-613 identified its target in this context to be KEAP1, revealing that this gene is selectively essential in the setting of EGFR inhibitor resistance. In-depth molecular characterization demonstrated that (1) MCB-613 binds KEAP1 covalently; (2) a single molecule of MCB-613 is capable of bridging two KEAP1 monomers together; and, (3) this modification interferes with the degradation of canonical KEAP1 substrates such as NRF2. Surprisingly, NRF2 knockout sensitizes cells to MCB-613, suggesting that the drug functions through modulation of an alternative KEAP1 substrate. Together, these findings advance MCB-613 as a new tool for exploiting the selective essentiality of KEAP1 in drug-resistant,EGFR-mutant NSCLC cells.
Applications of artificial intelligence in predicting dengue outbreaks in the face of climate change: a case study along coastal India
Authors: Tallam Krti , Quang Minh Pham 
Published: January 2023

AbstractThe climate crisis will have an increasingly profound effect on the global distribution and burden of infectious diseases. Climate-sensitive diseases can serve as critical case studies for assessing public health priorities in the face of epidemics. Preliminary results denote that machine learning-based predictive modeling measures can be successfully applied to understanding environmental disease transmission dynamics. Ultimately, machine learning models can be trained to detect climate-sensitive diseases early, diseases which might represent serious threats to human health, food safety, and economies. We explore how machine learning can serve as a tool for better understanding climate-sensitive diseases, taking dengue dynamics along the Godavari River of coastal India as our case study. We hypothesize that a climate-driven predictive model with controlled calibration can help us understand several of the most critical relationships and climate characteristics of climate-sensitive disease dynamics.
Aging and Alzheimer’s Disease Have Dissociable Effects on Medial Temporal Lobe Connectivity
Authors: Hrybouski Stanislau , Das Sandhitsu R. , Xie Long , Wisse Laura E. M. , Kelley Melissa , Lane Jacqueline , Sherin Monica , DiCalogero Michael , Nasrallah Ilya , Detre John A. , Yushkevich Paul A. , Wolk David A. 
Published: January 2023

ABSTRACTFunctional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer’s disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer’s disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer’s and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighborhood – the Anterior-Temporal and Posterior-Medial brain networks – in normal agers, individuals with preclinical Alzheimer’s disease, and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer’s disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted ‘U-shaped’ relationship between functional connectivity and Alzheimer’s stage. According to our results, the preclinical phase of Alzheimer’s disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbors in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer’s disease. Instead, patients with symptomatic Alzheimer’s disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (1) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (2) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and, (3) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer’s disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging vs. Alzheimer’s disease.
Reproducible growth ofBrachypodium distachyonin fabricated ecosystems (EcoFAB 2.0) reveals that nitrogen form and starvation modulate root exudation
Authors: Novak Vlastimil , Andeer Peter F. , Bowen Benjamin P. , Ding Yezhang , Zhalnina Kateryna , Tomaka Connor , Golini Amber N. , Kosina Suzanne M. , Northen Trent R. 
Published: January 2023

AbstractUnderstanding plant-microbe interactions requires examination of root exudation under nutrient stress using standardized and reproducible experimental systems. We grewBrachypodium distachyonhydroponically in novel fabricated ecosystem devices (EcoFAB 2.0) under three inorganic nitrogen forms (NO3−, NH4+, NH4NO3), followed by nitrogen starvation. Analyses of exudates with LC-MS/MS, biomass, medium pH, and nitrogen uptake showed EcoFAB 2.0’s low intra-treatment data variability. Furthermore, the three inorganic nitrogen forms caused differential exudation, generalized by abundant amino acids/peptides and alkaloids. Comparatively, N-deficiency decreased N-containing compounds but increased shikimates/phenylpropanoids. Subsequent bioassays with two shikimates/phenylpropanoids (shikimic andp-coumaric acids) on the rhizobacteriumPseudomonas putidaorBrachypodiumseedlings revealed that shikimic acid promoted bacterial and root growth, whilep-coumaric acid stunted seedlings. Our results suggest: (i)Brachypodiumalters exudation in response to nitrogen status, which can affect rhizobacterial growth; and (ii) EcoFAB 2.0 is a valuable standardized plant research tool.TeaserEcoFAB 2.0, a novel fabricated ecosystem device, has low data variability in studies of plant traits.
Phenome-wide analysis identifies parent-of-origin effects on the human methylome associated with changes in the rate of aging
Authors: Gao Chenhao , Amador Carmen , Walker Rosie M. , Campbell Archie , Madden Rebecca A , Adams Mark J. , Bai Xiaomeng , Liu Ying , Li Miaoxin , Hayward Caroline , Porteous David J. , Shen Xueyi , Evans Kathryn L. , Haley Chris S. , McIntosh Andrew M. , Navarro Pau , Zeng Yanni 
Published: January 2023

AbstractVariation in the rate at which humans age may be rooted in early life events acting through genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions either enriched for genetically controlled imprinting effects (the typical type of POE) or atypical POE introduced by environmental effects associated with parents. This part of the methylome is heavily influenced by early life events, making it a potential route connecting early environmental exposures, the epigenome and the rate of aging. Here, we aim to test the association of POE-influenced methylation of CpG dinucleotides (POE-CpG sites) with early and later environmental exposures and subsequently with health-related phenotypes and adult aging phenotypes. We do this by performing phenome-wide association analyses of the POE-influenced methylome using a large family-based population cohort (GS:SFHS, Ndiscovery=5,087, Nreplication=4,450). At the single CpG level, 92 associations of POE-CpGs with phenotypic variation were identified and replicated. Most of the associations were contributed by POE-CpGs belonging to the atypical class and the most strongly enriched associations were with aging (DNAmTL acceleration), intelligence and parental (maternal) smoking exposure phenotypes. We further found that a proportion of the atypical-POE-CpGs formed co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased internal module connectivity (strength of methylation correlation across constituent CpGs) with age. Atypical POE-CpGs also displayed high levels of methylation heterogeneity and epigenetic drift (i.e. information loss with age) and a strong correlation with CpGs contained within epigenetic clocks. These results identified associations between the atypical-POE-influenced methylome and aging and provided new evidence for the “early development of origin” hypothesis for aging in humans.
The co-occurrence of genetic variants in theTYRandOCA2genes confers susceptibility to albinism
Authors: Green David J. , Michaud Vincent , Lasseaux Eulalie , Plaisant Claudio ,   UK Biobank Eye and Vision Consortium, Fitzgerald Tomas , Birney Ewan , Black Graeme C. , Arveiler Benoît , Sergouniotis Panagiotis I. 
Published: January 2023

ABSTRACTAlthough rare genetic conditions are mostly caused by DNA sequence alterations that functionally disrupt individual genes, large-scale studies using genome sequencing have started to unmask additional complexity. Understanding how combinations of variants in different genes shape human phenotypes is expected to provide important insights into the clinical and genetic heterogeneity of rare disorders. We used albinism, an archetypal rare condition associated with hypopigmentation, as an exemplar for the study of genetic interactions. We analysed data from the Genomics England 100,000 Genomes Project alongside a cohort of 1,120 individuals with albinism, and investigated the effect of dual heterozygosity for the combination of two established albinism-related variants:TYR:c.1205G>A (p.Arg402Gln) [rs1126809] andOCA2:c.1327G>A (p.Val443Ile) [rs74653330]. As each of these changes alone is insufficient to cause disease when present in the heterozygous state, we sought evidence of synergistic effects. We found that, when both variants are present, the probability of receiving a diagnosis of albinism is significantly increased (odds ratio 12.8; 95% confidence interval 6.0 – 24.7; p-value 2.1 x 10-8). Further analyses in an independent cohort, the UK Biobank, supported this finding and highlighted that heterozygosity for theTYR:c.1205G>A andOCA2:c.1327G>A variant combination is associated with statistically significant alterations in visual acuity and central retinal thickness (traits that are considered albinism endophenotypes). The approach discussed in this report opens up new avenues for the investigation of oligogenic patterns in apparently Mendelian disorders.
Externally Validated Machine Learning Algorithm Accurately Predicts Medial Tibial Stress Syndrome in Military Trainees; A Multi-Cohort Study
Authors: Shaw Angus , Newman Phillip , Witchalls Jeremy , Hedger Tristan 
Published: January 2023

AbstractObjectivesMedial Tibial Stress Syndrome (MTSS) is a common musculoskeletal injury, both in sports and the military. There is no reliable treatment and reoccurrence rates are high. Prevention of MTSS is critical to reducing operational burden. Therefore, this study aimed to build a decision-making model to predict the individual risk of MTSS within officer cadets and test the external validity of the model on a separate military population.DesignProspective cohort study.MethodsThis study collected a suite of key variables previously established for predicting MTSS. Data was obtained from 107 cadets (34 females and 73 males). A follow-up survey was conducted at 3-months to determine MTSS diagnoses. Six ensemble learning algorithms were deployed and trained 5 times on random stratified samples of 75% of the dataset. The resultant algorithms were tested on the remaining 25% of the dataset and the models were compared for accuracy. The most accurate new algorithm was tested on an unrelated data sample of 123 Australian Navy recruits to establish external validity of the model.ResultsRandom Forest modelling was the most accurate in identifying a diagnosis of MTSS; (AUC = 98%). When the model was tested on an external dataset, it performed with an accuracy of 94% (F1= 0.88).ConclusionThis model is highly accurate in predicting those who will develop MTSS. The model provides important preventive capacity which should be trialled as a risk management intervention.