bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of anterior choroidal artery occlusion test under MEP monitoring for a recurrent internal carotid artery–anterior choroidal artery bifurcation aneurysm clipping
Authors: Suzuki Yosuke , Noda Kosumo , Yasuda Souichirou , Okada Yasuaki , Ono Syun , Kiko Katsunari , Yoshikawa Kohei , Miyoshi Norio , Kondo Tomomasa , Haraguchi Kenichi , Oda Jyunpei , Ota Nakao , Kamiyama Hiroyasu , Tokuda Sadahisa , Tanikawa Rokuya
Published: January 2023

A 59-year-old female with recurrent Anterior Choroidal Artery (AchA) aneurysm was elected for surgery at our institution through a standard pterional approach. Two thin perforating branches were found to origin from the dome of the aneurysm during operation, and therefore complete aneurysm clipping preserving these branches was not feasible. These perforating branches were temporarily occluded under motor-evoked potential (MEP) monitoring. The MEPs remained stable during 10 min of temporary clipping, and we concluded that these branches could be sacrificed, and therefore neck clipping was performed occluding these tiny AchA perforators. Although postoperative magnetic resonance imaging with diffusion-weighted images showed ischemic signs in left AchA territory after the operation, the patient remained asymptomatic and was discharged home with mRS 0.
Comprehensive spectroscopic and photometric study of pulsating eclipsing binary star AI Hya
Authors: Kahraman Aliçavuş F , Pawar T , Hełminiak K G , Handler G , Moharana A , Aliçavuş F , De Cat P , Leone F , Catanzaro G , Giarrusso M , Ukita N , Kambe E
Published: January 2023

The pulsating eclipsing binaries are remarkable systems that provide an opportunity to probe the stellar interior and to determine the fundamental stellar parameters precisely. Especially the detached eclipsing binary systems with (a) pulsating component(s) are significant objects to understand the nature of the oscillations since the binary effects in these systems are negligible. Recent studies based on space data have shown that the pulsation mechanisms of some oscillating stars are not completely understood. Hence, comprehensive studies of a number of pulsating stars within detached eclipsing binaries are important. In this study, we present a detailed analysis of the pulsating detached eclipsing binary system AI Hya which was studied by two independent groups with different methods. We carried out a spectroscopic survey to estimate the orbital parameters via radial velocity measurements and the atmospheric parameters of each binary component using the composite and/or disentangled spectra. We found that the more luminous component of the system is a massive, cool and chemically normal star while the hotter binary component is a slightly metal-rich object. The fundamental parameters of AI Hya were determined by the analysis of binary variations and subsequently used in the evolutionary modelling. Consequently, we obtained the age of the system as 850 ± 20 Myr and found that both binary components are situated in the δ Scuti instability strip. The frequency analysis revealed pulsation frequencies between 5.5 and 13.0 d−1 and we tried to estimate which binary component is the pulsating one. However, it turned out that those frequencies could originate from both binary components.
Timing the formation of the galactic thin disc with asteroseismic stellar ages
Authors: Wu Yaqian , Xiang Maosheng , Zhao Gang , Chen Yuqin , Bi Shaolan , Li Yaguang
Published: January 2023

The formation of the extended thin disc is the most spectacular event of our Galaxy in the past ∼8 Gyr. To unveil this process, obtaining precise and accurate stellar ages for a large sample of stars is essential although challenging. In this work, we present the asteroseismic age determination of 5306 red giant branch stars using Kepler and LAMOST data, with a thorough examination of how the age determination is affected by the choice of different temperature scales and stellar models. Thanks to the high precision of the asteroseismic and spectroscopic parameters of our sample stars, we are able to achieve age determination with an average accuracy of 12 per cent. However, the age determination is sensitively dependent on the adopted temperature scale, as 50 K difference in effective temperature may cause larger than 10 per cent systematic uncertainty in the age estimates. Using the ages derived with the most plausible set of the temperature scale, we study the age distribution of the chemical thin disc stars, and present an estimate of the formation epoch of the first Galactic thin disc stars. We find that the first (oldest) thin disc stars have an age of $9.5^{+0.5(\rm rand.)+0.5(\rm sys.)}_{-0.4(\rm rand.)-0.3(\rm sys.)}$ Gyr, where the systematic uncertainties reflect ages estimated using different stellar evolutionary models. At this epoch, the Galactic thick disc was still forming stars, indicating there is a time window when both the thin and thick discs of our Galaxy were forming stars together. Moreover, we find that the first thin disc stars exhibit a broad distribution of Galactocentric radii, suggesting that the inner and outer thin discs began to form simultaneously.
The impact of weak lensing on Type Ia supernovae luminosity distances
Authors: Shah Paul , Lemos Pablo , Lahav Ofer
Published: January 2023

When Type Ia supernovae are used to infer cosmological parameters, their luminosities are compared to those from a homogeneous cosmology. In this note, we propose a test to examine to what degree SN Ia have been observed on lines of sight where the average matter density is not representative of the homogeneous background. We apply our test to the Pantheon SN Ia compilation, and find two redshift bins which indicate a moderate bias to over-density at ∼2σ. We modify the Tripp estimator to explicitly de-lens SN Ia magnitudes, and show that this reduces scatter of Hubble diagram residuals. Using our revised Tripp estimator, the effect on cosmological parameters from Pantheon in ΛCDM is however small with a change in mean value from Ωm = 0.317 ± 0.027 (baseline) to Ωm = 0.312 ± 0.025 (de-lensed). For the Flat wCDM case, it is Ωm = 0.332 ± 0.049 and w = −1.16 ± 0.16 (baseline) versus Ωm = 0.316 ± 0.048 and w = −1.12 ± 0.15 (de-lensed). We note that the effect of lensing on cosmological parameters may be larger for future high-z surveys.
Structures of pMV158 replication initiator RepB with and without DNA reveal a flexible dual-function protein
Authors: Machón Cristina , Ruiz-Masó José A , Amodio Juliana , Boer D Roeland , Bordanaba-Ruiseco Lorena , Bury Katarzyna , Konieczny Igor , del Solar Gloria , Coll Miquel
Published: January 2023

DNA replication is essential to all living organisms as it ensures the fidelity of genetic material for the next generation of dividing cells. One of the simplest replication initiation mechanisms is the rolling circle replication. In the streptococcal plasmid pMV158, which confers antibiotic resistance to tetracycline, replication initiation is catalysed by RepB protein. The RepB N-terminal domain or origin binding domain binds to the recognition sequence (bind locus) of the double-strand origin of replication and cleaves one DNA strand at a specific site within the nic locus. Using biochemical and crystallographic analyses, here we show how the origin binding domain recognises and binds to the bind locus using structural elements removed from the active site, namely the recognition α helix, and a β-strand that organises upon binding. A new hexameric structure of full-length RepB that highlights the great flexibility of this protein is presented, which could account for its ability to perform different tasks, namely bind to two distinct loci and cleave one strand of DNA at the plasmid origin.
Differential Expression Enrichment Tool (DEET): an interactive atlas of human differential gene expression
Authors: Sokolowski Dustin J , Ahn Jedid , Erdman Lauren , Hou Huayun , Ellis Kai , Wang Liangxi , Goldenberg Anna , Wilson Michael D
Published: January 2023

Differential gene expression analysis using RNA sequencing (RNA-seq) data is a standard approach for making biological discoveries. Ongoing large-scale efforts to process and normalize publicly available gene expression data enable rapid and systematic reanalysis. While several powerful tools systematically process RNA-seq data, enabling their reanalysis, few resources systematically recompute differentially expressed genes (DEGs) generated from individual studies. We developed a robust differential expression analysis pipeline to recompute 3162 human DEG lists from The Cancer Genome Atlas, Genotype-Tissue Expression Consortium, and 142 studies within the Sequence Read Archive. After measuring the accuracy of the recomputed DEG lists, we built the Differential Expression Enrichment Tool (DEET), which enables users to interact with the recomputed DEG lists. DEET, available through CRAN and RShiny, systematically queries which of the recomputed DEG lists share similar genes, pathways, and TF targets to their own gene lists. DEET identifies relevant studies based on shared results with the user's gene lists, aiding in hypothesis generation and data-driven literature review.
mSigHdp: hierarchical Dirichlet process mixture modeling for mutational signature discovery
Authors: Liu Mo , Wu Yang , Jiang Nanhai , Boot Arnoud , Rozen Steven G
Published: January 2023

Mutational signatures are characteristic patterns of mutations caused by endogenous or exogenous mutational processes. These signatures can be discovered by analyzing mutations in large sets of samples—usually somatic mutations in tumor samples. Most programs for discovering mutational signatures are based on non-negative matrix factorization (NMF). Alternatively, signatures can be discovered using hierarchical Dirichlet process (HDP) mixture models, an approach that has been less explored. These models assign mutations to clusters and view each cluster as being generated from the signature of a particular mutational process. Here, we describe mSigHdp, an improved approach to using HDP mixture models to discover mutational signatures. We benchmarked mSigHdp and state-of-the-art NMF-based approaches on four realistic synthetic data sets. These data sets encompassed 18 cancer types. In total, they contained 3.5 × 107 single-base-substitution mutations representing 32 signatures and 6.1 × 106 small insertion and deletion mutations representing 13 signatures. For three of the four data sets, mSigHdp had the best positive predictive value for discovering mutational signatures, and for all four data sets, it had the best true positive rate. Its CPU usage was similar to that of the NMF-based approaches. Thus, mSigHdp is an important and practical addition to the set of tools available for discovering mutational signatures.
Unexpected giant negative area compressibility in palladium diselenide
Authors: Jiang Xingxing , Zhang Shengzi , Jiang Dequan , Wang Yonggang , Molokeev Maxim S , Wang Naizheng , Liu Youquan , Zhang Xingyu , Lin Zheshuai
Published: January 2023

Negative area compressibility (NAC) is a counterintuitive ‘squeeze–expand’ behavior in solids that is very rare but attractive due to possible pressure–response applications and coupling with rich physicochemical properties. Herein, NAC behavior is reported in palladium diselenide with a large magnitude and wide pressure range. We discover that, apart from the rigid flattening of layers that has been generally recognized, the unexpected giant NAC effect in PdSe2 largely comes from anomalous elongation of intralayer chemical bonds. Both structural variations are driven by intralayer-to-interlayer charge transfer with enhanced interlayer interactions under pressure. Our work updates the mechanical understanding of this anomaly and establishes a new guideline to explore novel compression-induced properties.
First finding of continental deep subduction in the Sesia Zone of the Western Alps and implications for subduction dynamics
Authors: Chen Yi-Xiang , Zhou Kun , He Qiang , Zheng Yong-Fei , Schertl Hans-Peter , Chen Kun
Published: January 2023

Continental deep subduction after the closure of large oceanic basins is commonly ascribed to the gravitational pull of the subducting oceanic slab. However, it is not clear how continental lithosphere adjacent to small oceanic basins was subducted to mantle depths. The Sesia Zone in the Western Alps provides an excellent target for exploration of subduction dynamics in such a tectonic setting. Here we report the first finding of coesite in a jadeite-bearing orthogneiss from the Sesia Zone, providing the first evidence for deep subduction of the continental crust to mantle depths for ultrahigh-pressure (UHP) metamorphism in this zone. Three coesite inclusions were identified by laser Raman spectroscopy in two garnet grains. Based on zircon U-Pb dating and trace element analysis, the UHP metamorphic age was constrained to be 76.0 ± 1.0 Ma. The phase equilibrium modeling yields peak metamorphic pressures of 2.8–3.3 GPa, demonstrating the continental deep subduction to mantle depths of >80 km. The subducted continental crust was a rifted hyperextended continental margin, which was converted to the passive continental margin during seafloor spreading and then deeply subducted during the oblique convergence between the Adria microplate and Eurasian plate in the Late Cretaceous. Because the slab pull could only play a limited role in closing small oceanic basins for continental collision, the distal push of either continental breakup or seafloor spreading is suggested as the major driving force for the deep subduction of continental crust in the Western Alps. Therefore, deep subduction of the continental crust bordering small oceanic basins would have been induced by the far-field stress of compression, whereas that bordering large oceanic basins was spontaneous due to the oceanic slab pull. This provides a new insight into the geodynamic mechanism of continental deep subduction.
Candidate Selection in Portugal
Authors: Jalali Carlos , Sanches Edalina Rodrigues
Published: January 2023

Candidate selection is one of the most important tasks performed by political parties in a democracy, and all the more so in closed-list proportional representation (CLPR) systems such as the one in Portugal. The choice of which individual politicians are included in the party lists and their chances of being elected rests in the hands of parties, shaping the make-up of parliament and of democratic representation. This chapter analyses the dynamics of candidate selection in Portugal, highlighting the parties’ combination of exclusive and centralized selection rules with more inclusive practices. Portugal is profiled as a crucial case that defies the expectations of centralized and exclusive selectorates with CLPR systems.
Autoregulation of blood flow drives early hypotension in a rat model of systemic inflammation induced by bacterial lipopolysaccharide
Authors: Moretti Eduardo H , Rodrigues Abner C , Marques Bruno V , Totola Leonardo T , Ferreira Caroline B , Brito Camila F , Matos Caroline M , da Silva Filipe A , Santos Robson A S , Lopes Luciana B , Moreira Thiago S , Akamine Eliana H , Baccala Luiz A , Fujita André , Steiner Alexandre A
Published: January 2023

Uncontrolled vasodilation is known to account for hypotension in the advanced stages of sepsis and other systemic inflammatory conditions, but the mechanisms of hypotension in earlier stages of such conditions are not clear. By monitoring hemodynamics with the highest temporal resolution in unanesthetized rats, in combination with ex-vivo assessment of vascular function, we found that early development of hypotension following injection of bacterial lipopolysaccharide is brought about by a fall in vascular resistance when arterioles are still fully responsive to vasoactive agents. This approach further uncovered that the early development of hypotension stabilized blood flow. We thus hypothesized that prioritization of the local mechanisms of blood flow regulation (tissue autoregulation) over the brain-driven mechanisms of pressure regulation (baroreflex) underscored the early development of hypotension in this model. Consistent with this hypothesis, an assessment of squared coherence and partial-directed coherence revealed that, at the onset of hypotension, the flow–pressure relationship was strengthened at frequencies (<0.2 Hz) known to be associated with autoregulation. The autoregulatory escape to phenylephrine-induced vasoconstriction, another proxy of autoregulation, was also strengthened in this phase. The competitive demand that drives prioritization of flow over pressure regulation could be edema-associated hypovolemia, as this became detectable at the onset of hypotension. Accordingly, blood transfusion aimed at preventing hypovolemia brought the autoregulation proxies back to normal and prevented the fall in vascular resistance. This novel hypothesis opens a new avenue of investigation into the mechanisms that can drive hypotension in systemic inflammation.
Evaluation of sterilisation techniques for 3D-printed implantable devices
Authors: Stewart Sarah A , Domínguez-Robles Juan , Donnelly Ryan F , Larrañeta Eneko
Published: January 2023

Objectives

This article investigates the potential use of microwave (MW) radiation, ultraviolet (UV)-light and gamma radiation for the sterilisation of 3D-printed implantable devices prepared using poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA).

Methods

Samples were sterilised using MW, UV and gamma radiation. Subsequently, the sterility of these samples was tested following the British Pharmacopeia test for sterility and controlled contamination test. Finally, sterilised samples were characterised (DSC, FTIR and drug release studies) to evaluate potential changes in their physicochemical properties during sterilisation.

Key findings

MW-radiation failed the British Pharmacopeia test for sterility. UV-light did not pass the British Pharmacopoeia test for sterility, but it showed promising results for the controlled contamination test (bacterial-contamination reduction >99.9%). These techniques did not modify the physicochemical properties of PLA. On the other hand, samples treated with gamma radiation passed the British Pharmacopeia sterility tests. However, the Tg and mechanical properties of the resulting samples were affected by gamma radiation. It is important to note that none of the sterilisation methods investigated in this article resulted in any change in the in vitro release results.

Conclusions

Only gamma radiation passed the British Pharmacopeia test for sterility. However, the UV method showed potential and should be further investigated.
Howard P. Roffwarg: sleep pioneer, legend, and ontogenetic hypothesis author
Authors: Shaffery James P , Marks Gerald A
Published: January 2023

Narrated in this article are accounts of the many contributions Howard P. Roffwarg, MD, made to the field of sleep research and sleep medicine across his entire professional career as a student, a mentor, a leader in the Sleep Research Society, a sleep medicine clinician, and a scientist who performed experimental investigations in humans and animals. Dr Roffwarg was the originator of what is known as the “Ontogenetic Hypothesis” of sleep. His research over many years on physiology has contributed greatly to much of the experimental support substantiating a role for rapid eye-movement sleep (REMS) in the early development of the brain. Though much is still unknown, the Ontogenetic Hypothesis, still to this day, inspires many neuroscientists in their investigations. These studies have demonstrated roles for both REMS and NREMS in development as well as on brain function throughout his life span. Dr Howard P. Roffwarg, is one of the legends in the field of sleep research.
Mesenchymal Stem Cell-Derived Exosomes Ameliorate Diabetic Kidney Disease Through the NLRP3 Signaling Pathway
Authors: Wang Yinghui , Liu Jiaxi , Wang Honggang , Lv Shasha , Liu Qingzhen , Li Shan , Yang Xue , Liu Gang
Published: January 2023

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Exosomes (Exo) derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) have been demonstrated to be an effective therapy for DKD, but the underlying mechanisms of this action remain poorly defined. We investigated the association of DKD with inflammasome activation and the pathophysiological relevance of Exo-mediated inflammation relief as well as damage repair in this progression. We co-cultured podocytes and HUC-MSCs derived Exo (MSCs-Exo) under high glucose (HG) and injected MSCs-Exo into diabetic mice, then we detected the NLRP3 inflammasome both in vitro and in vivo. We found that HG reduced the viability of podocytes, activated the NLRP3 signaling pathway and increased inflammation in podocytes and diabetic mice. MSCs-Exo attenuated the inflammation, including the expression of IL-6, IL-1β, IL-18, TNF-α; depressed the activation of NLRP3 signaling pathway in podocytes under HG and diabetic mice, ameliorated kidney injury. Furthermore, miR-22-3p, which is relatively highly expressed miRNAs in exosomes of MSCs, may be the key point in this progress, by suppressing the expression of its known target, NLRP3. Knocking down miR-22-3p from MSCs-Exo abolished their anti-inflammation activity and beneficial function both in vitro and in vivo. Collectively, our results have demonstrated that exosomes transferring miR-22-3p protected the podocytes and diabetic mice from inflammation by mediating NLRP3 inflammasome, indicating that MSC-derived exosomes may be a promising therapeutic cell-free strategy for DKD.
Lactation performance and feed utilization of Rahmani ewes fed with either a newly produced bacteriocin-like substance or a commercial bacteriocin
Authors: Azzaz Hossam H , Kholif Ahmed E , Abd El Tawab Ahmed M , El-Sherbiny Mohamed , Murad Hussein A , Hassaan Noha A , Vargas-Bello-Pérez Einar
Published: January 2023

The aim of the present study was to compare the effect of feeding a newly produced bacteriocin-like substance from Lactococcus lactis ssp. lactis (PNP) with a commercial bacteriocin (NISEEN-S; CNP) in lactating Rahmani ewe diets. In experiment 1, the effects of four levels (500, 1,000, 1,500, and 2,000 unit/kg substrate, dry matter (DM) basis) of both bacteriocins on in vitro ruminal fermentation kinetics, total gas production (TGP), methane production (CH4), and nutrient degradability were determined. In experiment 2, 2 wk before the expected parturition, 30 multiparous lactating Rahmani ewes (mean ± SD: 2 ± 0.3 parity, 46.8 ± 2.5 kg body weight, 23 ± 2.7 mo of age, and 370 ± 13 g/d of previous milk production) were equally divided into three treatments in a complete randomized design for 90 d. The ewes in the control treatment were offered a diet composed of 600 g of concentrate feed mixture, 300 g berseem hay, and 100 g of faba bean straw (Control), or supplemented with produced bacteriocin like substance (PNP) or commercial (CNP) bacteriocin at 500 unit/kg feed (DM basis). In experiment 1, both PNP and CNP linearly and quadratically decreased (P < 0.001) CH4 production; however, PNP and CNP at 500 unit/kg feed quadratically increased fiber degradability (P < 0.01). In experiment 2, both PNP and CNP increased (P < 0.05) nutrient digestibility, and ruminal total volatile fatty acids, acetate, and propionate, while decreasing ruminal ammonia-N. The PNP treatment increased (P < 0.05) blood total proteins and albumin, while PNP and CNP treatments increase serum glucose. Both PNP and CNP treatments increased (P < 0.05) daily milk production and milk efficiency, without affecting the concentration of milk components. Both PNP and CNP are recommended to improve feed utilization and milk production, with superior results detected for PNP at 500 unit/kg feed daily.
QuPath Analysis for CD30+ Cutaneous T-Cell Lymphoma
Authors: Cieslak Cassandra , Mitteldorf Christina , Krömer-Olbrisch Tanja , Kempf Werner , Stadler Rudolf
Published: January 2023

Background:

Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma, in which the expression of cluster of differentiation 30 (CD30)+ subtype can now be treated with the CD30 antibody conjugate brentuximab vedotin. Diagnostic methods are based on immunohistochemical (IHC) staining followed by manual assessment by pathologists, which is always a subjective calculation. QuPath, an open-source software for digital pathology image analysis, satisfies the requirements of objective approaches.

Methods:

Ten samples from mycosis fungoides patients with CD30 expression at different stages were stained for CD3 and CD30 by IHC staining, scanned, and quantitative analysis was performed using QuPath (version 2.1). Each slide was independently assessed by 3 board-certified dermatopathologists.

Results:

Individual estimates for CD30+/CD3+ cells varied among the individual histopathologists (mean coefficient of variation, 0.46; range, 0–0.78). QuPath analysis showed excellent separation between the positively stained cells for CD3 and CD30 IHC and other cells and tissue structures, although the results correlated strongly with the respective mean estimates of the 3 histopathologists (Pearson-R 0.93).

Conclusions:

The results show a high interobserver variability evaluation of IHC markers, although quantitative image analysis offer a significant advantage for comparison. This is not only relevant for clinical routine but also especially critical in therapeutic studies addressing targeted molecules.
Chondrosarcoma of the Chest Wall
Authors: Laitinen Minna K. , Kask Gilber , Laurila Katariina , Tukiainen Erkki J. , Rönty Mikko , Haapamäki Ville , Salo Juho T.K.
Published: January 2023

Introduction

Chondrosarcoma (CS) is most common primary osseous tumor of the chest wall. The aim of this study was to report results from surgical procedures and evaluate clinical factors predicting survival of patients with chest wall CSs treated in a single tertiary sarcoma center.

Materials and Methods

Fifty patients with primary CS located in the ribs and sternum were included. Details of the clinical data and oncological outcomes, including local recurrence (LR) and disease-specific survival (DSS), were collected.

Results

The tumor was primarily originated in the sternum in 6 patients (12.5%) and in ribs 2 to 11 in the remaining patients. Specimens were histologically graded 1 in 13 patients (26%), 2 in 28 (56%), 3 in 8 (16%), and 1 (2%) as mesenchymal grade 3 CS. R0 margins were obtained in all cases. Reconstruction was warranted in 47 (94%) cases. Local recurrence developed in 3 (6%) patients, and the median time to LR was 17 (range, 16–68) months. Eight (16%) patients developed metastasis. Increasing tumor volume was a statistically significant factor for reduction of DSS.

Conclusions

Chondrosarcoma of the chest wall can be treated effectively with clear margins, resulting in lower LR rate and higher DSS than CS of the extremities and pelvis. Metastasis of the chest wall mostly occurs in high-grade tumors, and the locations of the metastases differ greatly from those observed in CS of the extremities and pelvis. Metastases are commonly extrapulmonary, indicating the need for postoperative follow-up with multiple imaging modalities to monitor recurrence and metastases.
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

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

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

Targeted 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

The 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

Functional 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

Understanding 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.

Teaser

EcoFAB 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

Variation 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.