bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact Oncoplastic Reduction Has on Long-Term Recurrence in Breast Conservation Therapy
Authors: Losken Albert , Smearman Erica L. , Hart Alexandra M. , Broecker Justine S. , Carlson Grant W. , Styblo Toncred M. 
Published: March 2022

Background:
The use of oncoplastic reduction techniques have many proven benefits over lumpectomy alone in the management of women with breast cancer. The impact it has on tumor recurrence is unclear. The purpose of this review was to evaluate the incidence of recurrence in patients who underwent oncoplastic reduction techniques compared to lumpectomy alone.

Methods:
A prospectively maintained database of patients at Emory Hospital who underwent oncoplastic reduction techniques at the time of tumor resection was queried. These patients were compared to a series of patients who had lumpectomy alone over a similar period. For inclusion in the study, patients were at least 10 years since the time of the tumor resection. The main outcome of interest was tumor recurrence.

Results:
There were 97 patients in the lumpectomy-only group and 95 patients in the oncoplastic reduction group, with an average follow-up of 7.8 years and 8.5 years, respectively. Patients in the oncoplastic group were younger (lumpectomy only, 61.4 years; oncoplastic reduction, 51.6 years; p < 0.001) and had larger tumors (lumpectomy only, 1.1 cm; oncoplastic reduction, 1.6 cm; p < 0.001). Local recurrence was 13 percent in the lumpectomy-only group and 9 percent in the oncoplastic reduction group (p = 0.34), and overall recurrence rates were similar (lumpectomy only, 15 percent; oncoplastic reduction, 24 percent; p = 0.13). Overall, surgical intervention (lumpectomy alone versus oncoplastic reduction) was not associated with local recurrence or any recurrence on univariate and multivariate analyses.

Conclusion:
Despite the oncoplastic reduction patients having a higher risk of recurrence and a more generous tumor resection, the long-term recurrence rates were equivalent when compared to breast-conserving therapy alone.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Reverse Lymphatic Mapping and Immediate Microsurgical Lymphatic Reconstruction Reduces Early Risk of Breast Cancer–Related Lymphedema
Authors: Weinstein Brielle , Le Nicole K. , Robertson Ellen , Zimmerman Amanda , Tavares Tina , Tran Thanh , Laronga Christine , Panetta Nicholas J. 
Published: March 2022

Background:
Breast cancer–related lymphedema is a progressive disease that poses tremendous physical, psychosocial, and financial burden on patients. Immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection is emerging as a potential therapeutic paradigm to decrease the incidence of breast cancer–related lymphedema in high-risk patients.

Methods:
Eighty-one consecutive patients underwent reverse lymphatic mapping and, when feasible, supermicrosurgical immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection at a tertiary care cancer center. Patients were followed prospectively in a multidisciplinary lymphedema clinic (plastic surgery, certified lymphatic therapy, dietary, case management) at 3-month intervals with clinical examination, circumferential limb girth measurements, and bioimpedance spectroscopy. An institutional control cohort was assessed for the presence of objectively diagnosed and treated breast cancer–related lymphedema. Data were analyzed by a university statistician.

Results:
Seventy-eight patients met inclusion, and 66 underwent immediate lymphaticovenular anastomosis. Mean follow-up was 250 days. When compared to a retrospective control group, the rate of lymphedema in patients who underwent immediate lymphaticovenular anastomosis was significantly lower (6 percent versus 44 percent; p < 0.0001). Patients with 6-month follow-up treated with combined adjuvant radiation therapy and chemotherapy had significantly greater risk of developing breast cancer–related lymphedema (p = 0.04) compared to those without combined adjuvant therapy. Arborized anastomotic technique had a statistically shorter operative time than end-to-end anastomosis (p = 0.005).

Conclusions:
This series of consecutive patients demonstrate a 6 percent incidence of early-onset breast cancer–related lymphedema with immediate lymphaticovenular anastomosis and an increased risk in those undergoing combined adjuvant treatment. These early data represent an encouraging and substantial decrease of breast cancer–related lymphedema in high-risk patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Liver Stiffness Is Markedly Decreased After Chronic Hepatitis C Treatment
Authors: Gulumsek Erdinc , Sumbul Hilmi Erdem , Buyuksimsek Mahmut , Demir Kubra , Koc Ayse Selcan , Tas Adnan , Bulut Yurdaer , Kara Banu 
Published: March 2022

Aim
The aim of the study was to demonstrate the liver stiffness (LS) change in chronic hepatitis C (CHC) patients obtained by elastography point quantification technique in before and after antiviral treatment (AVT).

Material and Methods
This prospective study included 84 patients diagnosed with CHC who had not previously received treatment for CHC and who had an indication for using direct-acting AVT. Necessary measurements were recorded with noninvasive liver fibrosis (LF) examinations. Posttreatment control of patients was carried out (ombitasvir + paritaprevir + ritonavir) + 3 months after the start of treatment for those treated with dasabuvir and 6 months after the start of treatment for patients treated with sofosbuvir + ribavirin. Liver stiffness changed after AVT is accepted as (Δ-LS), LS before AVT–LS after AVT.

Results
Basal LS was found to decrease significantly after AVT (8.00 ± 2.56 kPa vs 6.95 ± 2.86 kPa, P < 0.05). Similar aspartate aminotransferase–to–platelet ratio index and platelet number fibrosis 4 indices were observed before and after AVT (P > 0.05). It was observed that Δ-LS value after AVT was lower in patients with Child-Pugh class A cirrhosis than patients without cirrhosis (P < 0.05). In the comparison between Δ-LS value after AVT and LF score determined by liver biopsy, it was seen that the greatest Δ-LS value was in patients with fibrosis score of 3. An independent relationship was found between Δ-LS after AVT and LF score determined by biopsy (P < 0.05).

Conclusions
The LS value determined by the elastography point quantification technique is more effective than other noninvasive laboratory methods in demonstrating the CHC treatment response in clinical practice.
Late Pleistocene shell midden microstratigraphy indicates a complex history of human–environment interactions in the uplands of northern Vietnam
Authors: McAdams Conor , Morley Mike W. , Fu Xiao , Kandyba Alexander V. , Derevianko Anatoly P. , Nguyen Dong Truong , Doi Nguyen Gia , Roberts Richard G. 
Published: March 2022

Northern Vietnam is situated on a major route of Pleistocene hominin dispersal in East Asia, and the area's karstic caves preserve many prehistoric shell middens. Fossil and genomic evidence suggest a complex human history in this region and more widely across Southeast Asia and southern China, but related archaeological investigations are hampered by challenging site stratigraphies. Recent investigations of shell middens in other geographical settings have revealed the microstratigraphic complexity of these anthropogenic deposits. But caves promote distinctive site formation processes, while tropical climates may catalyse geomorphic and diagenetic changes. These environmental factors complicate the interpretation of northern Vietnam's shell middens and constraining their effects upon the formation, preservation and destruction of these sites is critical to understanding the archaeology of this region. We examine two archaeological cave sites, dated to the Late Pleistocene and located in the limestone uplands surrounding the Hanoi Basin. Each contains multiple shell midden layers associated with prehistoric occupation and burials. Using thin-section micromorphology (microstratigraphy), we reconstruct the depositional and post-depositional histories of these sites, presenting a geoarchaeological framework of interpretation that is applicable to shell middens in mainland Southeast Asia and tropical zones more widely. This work represents a further step towards improving our understanding of prehistoric human dispersals and adaptations in this region.
This article is part of the theme issue ‘Tropical forests in the deep human past’.
Ice Age megafauna rock art in the Colombian Amazon?
Authors: Iriarte José , Ziegler Michael J. , Outram Alan K. , Robinson Mark , Roberts Patrick , Aceituno Francisco J. , Morcote-Ríos Gaspar , Keesey T. Michael 
Published: March 2022

Megafauna paintings have accompanied the earliest archaeological contexts across the continents, revealing a fundamental inter-relationship between early humans and megafauna during the global human expansion as unfamiliar landscapes were humanized and identities built into new territories. However, the identification of extinct megafauna from rock art is controversial. Here, we examine potential megafauna depictions in the rock art of Serranía de la Lindosa, Colombian Amazon, that includes a giant sloth, a gomphothere, a camelid, horses and three-toed ungulates with trunks. We argue that they are Ice Age rock art based on the (i) naturalistic appearance and diagnostic morphological features of the animal images, (ii) late Pleistocene archaeological dates from La Lindosa confirming the contemporaneity of humans and megafauna, (iii) recovery of ochre pigments in late Pleistocene archaeological strata, (iv) the presence of most megafauna identified in the region during the late Pleistocene as attested by archaeological and palaeontological records, and (v) widespread depiction of extinct megafauna in rock art across the Americas. Our findings contribute to the emerging picture of considerable geographical and stylistic variation of geometric and figurative rock art from early human occupations across South America. Lastly, we discuss the implications of our findings for understanding the early human history of tropical South America.
This article is part of the theme issue ‘Tropical forests in the deep human past’.
DENSS-Multiple: A Structure Reconstruction Method using Multiple Contrast Variation of Small-Angle Neutron Scattering Based on the DENSS Algorithm
Authors: Sumner Jacob , Qian Shuo 
Published: March 2022

AbstractSmall-angle neutron scattering (SANS) provides easily manipulable neutron contrast variation that has been widely exploited to study the structure and function of biological macromolecules and their complex in solution. Here, we developed a method called DENSS-Multiple based on the DENSS (DENsity from Solution Scattering) algorithm to provide ab initio structure reconstruction with SANS contrast variation data. This new tool can exploit additional information in different SANS contrasts for improved ab initio reconstruction results.
In vivoassessment of mechanical properties during axolotl development and regeneration using confocal Brillouin microscopy
Authors: Riquelme-Guzmán Camilo , Beck Timon , Edwards-Jorquera Sandra , Schlüßler Raimund , Müller Paul , Guck Jochen , Möllmert Stephanie , Sandoval-Guzmán Tatiana 
Published: March 2022

ABSTRACTIn processes such as development and regeneration, where large cellular and tissue rearrangements occur, cell fate and behavior are strongly influenced by tissue mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures mechanical parameters optically with high resolution in a contact-free and label-free fashion. In this work, we took advantage of this tool and the transparency of the highly regenerative axolotl to probe its mechanical propertiesin vivofor the first time. We mapped the Brillouin frequency shift with high resolution in developing limbs and regenerating digits, the most studied structures in the axolotl. We detected a gradual increase in the cartilage Brillouin frequency shift, suggesting decreasing tissue compressibility during both development and regeneration. Moreover, we were able to correlate such increase with the regeneration stage, which was undetected with fluorescence microscopy imaging. The present work evidences the potential of Brillouin microscopy to unravel the mechanical changes occurringin vivoin axolotls, setting the basis to apply this technique in the growing field of epimorphic regeneration.
Automatic determination of the handedness of Single-Particle maps of macromolecules solved by CryoEM
Authors: Condado J. Garcia , Muñoz-Barrutia A. , Sorzano C.O.S. 
Published: March 2022

AbstractSingle-Particle Analysis by Cryo-Electron Microscopy is a well-established technique to elucidate the three-dimensional (3D) structure of biological macromolecules. The orientation of the acquired projection images must be initially estimated without any reference to the final structure. In this step, algorithms may find a mirrored version of all the orientations resulting in a mirrored 3D map. It is as compatible with the acquired images as its unmirrored version from the image processing point of view, only that it is not biologically plausible.In this article, we introduce HaPi (Handedness Pipeline), the first method to automatically determine the hand of electron density maps of macromolecules solved by CryoEM. HaPi is built by training two 3D convolutional neural networks. The first determines α-helices in a map, and the second determines whether the α-helix is left-handed or right-handed. A consensus strategy defines the overall map hand. The pipeline is trained on simulated and experimental data. The handedness can be detected only for maps whose resolution is better than 5Å. HaPi can identify the hand in 89% of new simulated maps correctly. Moreover, we evaluated all the maps deposited at the Electron Microscopy Data Bank and 11 structures uploaded with the incorrect hand were identified.
A primary patient-derived model for investigating functional heterogeneity within the human Leukemic Stem Cell Compartment
Authors: Boutzen Héléna , Chan-Seng-Yue Michelle , Murison Alex , Mbong Nathan , Wagenblast Elvin , Arlidge Christopher , Tonekaboni Seyed Ali Madani , Orouji Elias , Arruda Andrea , Mitchell Amanda , Notta Faiyaz , Lupien Mathieu , Minden Mark D. , Kaufmann Kerstin B. , Dick John E. 
Published: March 2022

AbstractThe ability of leukemic stem cells (LSC) to evade therapy and fuel leukemic progression causing relapse impedes therapeutic success in acute myeloid leukemia (AML). The LSC pool within a patient sample is not homogenous but comprises distinct LSC subsets that vary in self-renewal and propagation properties. The stemness programs that underlie LSC types are poorly understood since human LSC studies require primary patient samples where LSC numbers are low and isolation methods impure. To overcome these challenges, we developed a patient-derived AML model system (OCI-AML22) displaying a functionally, transcriptionally and epigenetically defined cellular hierarchy driven by functional LSCs that can be immunophenotypically identified and isolated. Through single cell and functional approaches, the OCI-AML22 LSC fraction was found to contain distinct LSCs that vary in proliferative and differentiation properties. OCI-AML22 represents a valuable resource to decipher mechanisms driving stemness and the multiple layers of heterogeneity within LSCs.
Macro-Chemical Biology: Engineering Biomimetic Trogocytosis with Farnesylated Chemically Self-Assembled Nanorings
Authors: Wang Yiao , Rozumalski Lakmal , Lichtenfels Caitlin , Petersberg Jacob R. , Kilic Ozgun , Distefano Mark D. , Wagner Carston R. 
Published: March 2022

AbstractWith the recent success of cell-based therapies, there has been a rapidly emerging interest in the engineering of cell-cell interactions and communications. Inspired by the natural intercellular material transfer process of trans-endocytosis or trogocytosis, we proposed that targeted farnesylated chemically self-assembled nanorings (farnesyl-CSANs) could serve as a biomimetic trogocytosis vehicle for engineering directional cargo transfer between cells; thus, allowing cell-cell interactions to be monitored, as well as facilitating communication between the cells by delivery of bioactive species. The membranes of sender cells were stably modified by hydrophobic insertion with the targeted farnesyl-CSANs and to be efficiently transferred to receiver cells expressing the appropriate receptor by endocytosis. CSAN-assisted cell-cell cargo transfer (C4T) was demonstrated to be receptor-specific and dependent on direct cell-cell interactions, the rate of receptor internalization and the amount of receptor expression. In addition, C4T was shown to facilitate cell-to-cell delivery of an apoptosis inducing drug, as wells as antisense oligonucleotides (ASO). Taken together, the C4T approach is a potentially versatile biomimetic trogocytosis platform that can be used to monitor cell-cell interactions, as well as the engineering of cell-cell communications, such as cell-based drug delivery.
Cross-comparison of state of the art neuromorphological simulators on modern CPUs and GPUs using the Brain Scaffold Builder
Authors: De Schepper R. , Akar N. Abi , Hater T. , Huisman B. F. B. , D’Angelo E. , Morrison A. , Casellato C. 
Published: March 2022

ABSTRACTA variety of software simulators exist for neuronal networks, and a subset of these tools allow the scientist to model neurons in high morphological detail. The scalability of such simulation tools over a wide range in neuronal networks sizes and cell complexities is predominantly limited by effective allocation of components of such simulations over computational nodes, and the overhead in communication between them. In order to have more scalable simulation software, it is therefore important to develop a robust benchmarking strategy that allows insight into specific computational bottlenecks for models of realistic size and complexity. In this study, we demonstrate the use of the Brain Scaffold Builder (BSB; De Schepper et al., 2021) as a framework for performing such benchmarks. We perform a comparison between the well-known neuromorphological simulator NEURON (Carnevale and Hines, 2006), and Arbor (Abi Akar et al., 2019), a new simulation library developed within the framework of the Human Brain Project. The BSB can construct identical neuromorphological and network setups of highly spatially and biophysically detailed networks for each simulator. This ensures good coverage of feature support in each simulator, and realistic workloads. After validating the outputs of the BSB generated models, we execute the simulations on a variety of hardware configurations consisting of two types of nodes (GPU and CPU). We investigate performance of two different network models, one suited for a single machine, and one for distributed simulation. We investigate performance across different mechanisms, mechanism classes, mechanism combinations, and cell types. Our benchmarks show that, depending on the distribution scheme deployed by Arbor, a speed-up with respect to NEURON of between 60 and 400 can be achieved. Additionally Arbor can be up to two orders of magnitude more energy efficient.
Dopaminergic modulation of dynamic emotion perception
Authors: Schuster B.A. , Sowden S. , Rybicki A.J. , Fraser D.S. , Press C. , Holland P. , Cook J.L. 
Published: March 2022

AbstractEmotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson’s disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioural modulation. Interestingly, whilst a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition.Significance statementA high prevalence of emotion recognition difficulties amongst clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.
Spatial Transcriptomics-based Identification of Molecular Markers for Nanomedicine Distribution in Tumor Tissue
Authors: Park Jeong-Bin , Choi Jin-Yeong , Choi Hongyoon , Im Hyung-Jun 
Published: March 2022

AbstractThe intratumoral accumulation of nanomedicine has been considered a passive process, referred to as the enhanced permeability and retention (EPR) effect. Recent studies have suggested that the tumor uptake of nanomedicines follows an energy-dependent pathway rather than being a passive process. Herein, to explore the factor candidates that are associated with nanomedicine tumor uptake, we developed a molecular marker identification platform by integrating microscopic fluorescence images of a nanomedicine distribution with spatial transcriptomics (ST) information. When this approach is applied to PEGylated liposomes, molecular markers related to hypoxia, glucose metabolism and apoptosis can be identified as being related to the intratumoral distribution of the nanomedicine. We expect that our method can be applied to explain the distribution of a wide range of nanomedicines and that the data obtained from this analysis can enhance the precise utilization of nanomedicines.