bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperbaric Oxygen Therapy for Threatened Nipple-Sparing Mastectomy Flaps
Authors: Nasr Hani Y. , Rifkin William J. , Muller John N. , Chiu Ernest S. 
Published: March 2023

Background
Nipple-sparing mastectomy (NSM) is emerging as the standard of care for treatment of breast cancer because of its oncologic safety and superior aesthetic outcomes. However, ischemia or necrosis of the skin flap and/or nipple-areola complex remain frequent complications. Hyperbaric oxygen therapy (HBOT) has emerged as a potential adjunct for flap salvage, although it is not currently a widely accepted practice. Here we review our institution's experience using a protocol of HBOT in patients with signs of flap ischemia or necrosis after NSM.

Methods
Retrospective review identified all patients treated with HBOT at our institution's hyperbaric and wound care center because of signs of ischemia after NSM. Treatment parameters consisted of 90-minute dives at 2.0 atmosphere once or twice daily. Patients unable to tolerate dives were considered a treatment failure, whereas those lost to follow-up were excluded from analysis. Patient demographics, surgical characteristics, and treatment indications were recorded. Primary outcomes assessed were flap salvage (no operative revision), need for revision procedures, and treatment complications.

Results
A total of 17 patients and 25 breasts met the inclusion criteria. The mean ± SD time to initiation of HBOT was 9.47 ± 12.7 days. The mean ± SD age was 46.7 ± 10.4 years, and mean ± SD follow-up time was 36.5 ± 25.6 days. Indications for NSM included invasive cancer (41.2%), carcinoma in situ (29.4%), and breast cancer prophylaxis (29.4%). Initial reconstruction included tissue-expander placement (47.1%), autologous reconstruction with deep inferior epigastric flaps (29.4%), and direct-to-implant reconstruction (23.5%). Hyperbaric oxygen therapy indications included ischemia or venous congestion for 15 breasts (60.0%) and partial thickness necrosis for 10 breasts (40.0%). Flap salvage was achieved in 22 of 25 breasts (88.0%). Reoperation was required for 3 breasts (12.0%). Hyperbaric oxygen therapy–related complications were observed in 4 patients (23.5%), which included 3 patients with mild ear pain and 1 patient with severe sinus pressure leading to treatment abortion.

Conclusions
Nipple-sparing mastectomy is an invaluable tool for breast and plastic surgeons to achieve oncologic and cosmetic goals. However, ischemia or necrosis of the nipple-areola complex or mastectomy skin flap remains frequent complications. Hyperbaric oxygen therapy has emerged as a possible intervention for threatened flaps. Our results demonstrate the utility of HBOT in this population to achieve excellent NSM flap salvage rates.
Efficacy of Immediate Lymphatic Reconstruction in Prevention of Breast Cancer–Related Lymphedema
Authors: Le Nicole K. , Liu Langfeier , Jesus Cruz Rachel , Parikh Jeegan , Rotatori Robert M. , Wainwright D’Arcy J. , Weinstein Brielle , Tavares Tina , Panetta Nicholas J. 
Published: March 2023

Introduction
Breast cancer–related lymphedema (BCRL) is a chronic condition that can negatively affect the quality of life of breast cancer survivors. Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection is emerging as a technique for the prevention of BCRL. This study compared the incidence of BRCL in patients who received ILR and those who were not amenable to ILR.

Methods
Patients were identified through a prospectively maintained database between 2016 and 2021. Some patients were deemed nonamenable to ILR due to a lack of visualized lymphatics or anatomic variability (eg, spatial relationships or size discrepancies). Descriptive statistics, independent t test, and Pearson χ2 test were used. Multivariable logistic regression models were created to assess the association between lymphedema and ILR. A loose age-matched subsample was created for subanalysis.

Results
Two hundred eighty-one patients were included in this study (252 patients who underwent ILR and 29 patients who did not). The patients had a mean age of 53 ± 12 years and body mass index of 28.6 ± 6.8 kg/m2. The incidence of developing lymphedema in patients with ILR was 4.8% compared with 24.1% in patients who underwent attempted ILR without lymphatic reconstruction (P = 0.001). Patients who did not undergo ILR had significantly higher odds of developing lymphedema compared with those who had ILR (odds ratio, 10.7 [3.2–36.3], P < 0.001; matched OR, 14.2 [2.6–77.9], P < 0.001).

Conclusions
Our study showed that ILR was associated with lower rates of BCRL. Further studies are needed to determine which factors place patients at highest risk of developing BCRL.
Bacterial Growth in Unsealed Bone-grafting Products
Authors: Shmuly Tom , Hater Amer , Bar-Ness Greenstein Ronit , Allon Dror Michael 
Published: March 2023

Objective:
The aim of this study was to simulate reusing an opened package of bone substitute (BS) under typical clinical conditions, by analyzing bacterial growth in samples of resealed packages of alloplast and xenograft BS following different time periods up to a week.

Materials and Methods:
The experiment was performed in 2 stages: dry stage and wet stage. In the dry stage, BS samples were exposed to air for 15 minutes and then were sealed again in their original package. After several “aging” periods [no aging (t0), 24 hours (t1), and 1 week (t7)], BS samples were plated onto brain heart infusion agar and were incubated at 37 °C for 24 hours under aerobic conditions. Bacterial colonies were enumerated and colony forming units per 1 mL was calculated. In the wet stage, the experiment was repeated but BSs were left to age in a brain heart infusion broth to simulate a more supporting humid environment to encourage bacterial growth.

Results:
In the dry stage of the experiment, no bacterial growth was detected in both xenograft and alloplast samples (colony forming units/mL=0), in any of the time points (t0, t1, t7). In the wet stage, average bacterial growth was 0 for both groups in t0. In t1: 1.14 × 104±4.16 × 103 for the xenograft and 7.73 × 105± 9.99 × 105 for the alloplast. In t7: 1.64 × 109±1.82 × 108 in the xenograft compared with 8.86 × 108±4.00 × 108 for the alloplast. Analysis of variance with repeated measures showed a significant difference in comparison of the 2 BSs for each time group (t1 and t7) (P<0.005).

Conclusion:
Under dry conditions, in a resealed package, there was no bacterial growth for up to 1 week for both BSs. Once the BSs are introduced to a humid environment, which supports bacterial growth, the xenograft BS allowed more rapid bacterial growth, compared with the alloplastic BS.
Robot-Assisted Nasal Reconstruction: A Cadaveric Study
Authors: Smith Corey , Fowler James , Ferreira Louis , Moore Corey 
Published: March 2023

Objective:
Manual contouring of cartilage for nasal reconstruction is tedious and time-consuming. The use of a robot could improve the speed and precision of the contouring process. This cadaveric study evaluates the efficiency and accuracy of a robot methodology for contouring the lower lateral cartilage of the nasal tip.

Methods:
An augmented robot with a spherical burring tool attached was utilized to carve 11 cadaveric rib cartilage specimens. In phase 1, the right lower lateral cartilage was harvested from a cadaveric specimen and used to define a carving path for each rib specimen. In phase 2, the cartilage remained in situ during the scanning and 3-dimensional modeling. The final carved specimens were compared with the preoperative plans through topographical accuracy analysis. The contouring times of the specimens were compared with 14 retrospectively reviewed cases (2017–2020) by an experienced surgeon.

Results:
Phase 1 root mean square error of 0.40±0.15 mm and mean absolute deviation of 0.33±0.13 mm. Phase 2 root mean square error of 0.43 mm and mean absolute deviation of 0.28 mm. The average carving time for the robot specimens was 14±3 minutes and 16 minutes for Phase 1 and Phase 2, respectively. The average manual carving by an experienced surgeon was 22±4 minutes.

Conclusions:
Robot-assisted nasal reconstruction is very precise and more efficient than manual contouring. This technique represents an exciting and innovative alternative for complex nasal reconstruction.
Inferring functional organization of posterior parietal cortex circuitry based on information flow
Authors: Kang Jung Uk , Mooshagian Eric , Snyder Lawrence H. 
Published: March 2023

AbstractMany studies infer the role of neurons by asking what information can be decoded from their activity or by observing the consequences of perturbing their activity. An alternative approach is to consider information flow between neurons. We applied this approach to the Parietal Reach Region (PRR) and the Lateral Intraparietal area (LIP) in posterior parietal cortex. Two complementary methods show that, across a range of reaching tasks, information flows primarily from PRR to LIP but not vice versa. This suggests that PRR determines the spatial goals of coordinated eye and arm movements and instructs LIP of those goals. Based on these findings, we conclude that PRR and LIP operate in a parallel rather than hierarchical manner to plan arm and eye movements, respectively. Similar methodology can be applied to other areas to infer their relative relationships.
Discrepancies in patient and caregiver ratings of personality change in Alzheimer’s disease and related dementias
Authors: Rhodes Emma , Mechanic-Hamilton Dawn , Phillips Jeffrey S. , McMillan Corey , Bahena Alejandra , Vitali Nykko , Hlava Quinn , Cook Philip , Gee James , Grossman Murray , Massimo Lauren 
Published: March 2023

AbstractBackgroundAssessment of personality change in Alzheimer’s disease and related dementias (ADRD) is clinically meaningful but complicated by patient (i.e., reduced insight) and informant (i.e., caregiver burden) factors that confound accurate reporting of personality traits. This study assessed the impact of caregiver burden on informant report of Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness) and investigated regional cortical volumes associated with larger discrepancies in patient and informant report of Big Five personality traits.MethodsSixty-four ADRD participants with heterogeneous neurodegenerative clinical phenotypes and their informants completed the Big Five Inventory (BFI). Caregiver burden was measured using the Zarit Burden Interview (ZBI). Discrepancy scores were computed as the absolute value of the difference between patient and informant ratings for all BFI trait scores and summed to create a global score. Regional grey matter volumes from T1-weighted 3T MRI were normalized to intracranial volume and related to global Big Five discrepancy scores using linear regression.ResultsHigher levels of caregiver burden were associated with higher informant ratings of patient Neuroticism (ß =0.27, p =.016) and lower informant ratings of patient Agreeableness (ß =-0.32, p =.002), Conscientiousness (ß =-0.3, p =.002), and Openness (ß =-0.34, p =.003) independent of disease severity. Patients with greater Big Five discrepancy scores showed smaller cortical volumes in right medial PFC (β = -0.00015,p= .002), right superior temporal gyrus (β = -0.00028,p= .025), and left inferior frontal gyrus (β = -0.00006p= .013).ConclusionsInformant ratings of personality traits in ADRD can be confounded by caregiver burden, highlighting the need for more objective measures of personality and behavior in dementia samples. Discrepancies between informant and patient ratings of personality may additionally reflect loss of insight secondary to cortical atrophy in frontal and temporal structures.
Constraint-based modeling predicts metabolic signatures of low- and high-grade serous ovarian cancer
Authors: Meeson Kate E. , Schwartz Jean-Marc 
Published: March 2023

AbstractOvarian cancer is an aggressive, heterogeneous disease, burdened with late diagnosis and resistance to chemotherapy. Clinical features of ovarian cancer could be explained by investigating its metabolism, and how the regulation of specific pathways link to individual phenotypes. Ovarian cancer is of particular interest for metabolic research due to its heterogeneous nature, with five distinct subtypes having been identified, each of which may display a unique metabolic signature. To elucidate metabolic differences, constraint-based modeling (CBM) represents a powerful technology, inviting the integration of ‘omics’ data, such as transcriptomics. However, many CBM methods have not prioritised accurate growth rate predictions, and there are very few ovarian cancer genome-scale studies, thus highlighting a niche in disease research. Here, a novel method for constraint-based modeling has been developed, employing the genome-scale model Human1 and flux balance analysis (FBA), enabling the integration ofin vitrogrowth rates, transcriptomics data and media conditions to predict the metabolic behaviour of cells. Using low- and high-grade ovarian cancer as a case study, subtype-specific metabolic differences have been predicted, which have been supported with CRISPR-Cas9 data and an extensive literature review. Metabolic drivers of aggressive phenotypes, as well as pathways responsible for increased proliferation and chemoresistance in low-grade cell lines have been suggested. Experimental gene dependency data has been used to validate fatty acid biosynthesis and the pentose phosphate pathway as essential for low-grade cellular growth, highlighting potential vulnerabilities for this ovarian cancer subtype.
Knockout of αβ but not γδ T cells in chickens is associated with high cytotoxicity and deficiency of regulatory and helper T cells
Authors: von Heyl Theresa , Klinger Romina , Aumann Dorothea , Zenner Christian , Alhussien Mohanned , Schlickenrieder Antonina , Lengyel Kamila , Vikkula Hanna-Kaisa , Mittermair Teresa , Sid Hicham , Schusser Benjamin 
Published: March 2023

AbstractThe availability of genetically modified mice has facilitated the study of mammalian T cells. No model has yet been developed to study these cells in chicken, an important livestock species with a high availability of γδ T cells. To investigate the role of γδ and αβ T cell populations in birds, we generated chickens lacking these T cell populations. This was achieved by genomic deletion of the constant region of the T cell receptor γ or αβ chain, leading to a complete loss of either γδ or αβ T cells. Our results show that a deletion of αβ T cells but not γδ T cells resulted in a severe phenotype in knockout chickens. The αβ T cell knockout chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of αβ T cell knockout chickens revealed a significant increase in monocytes and the absence of CD4+T cells and FoxP3+regulatory T cells compared to wild type chickens. In addition, we observed a significant decrease in immunoglobulins, B lymphocytes, and changes in the bursa morphology. Our data reveal the consequences of T cell knockouts in chickens and provide new insights into their function in vertebrates.Significance statementThe lack of genetically modified chickens has severely limited research in avian immunology compared to other animal models. Here, we report the generation of two T cell knockout chicken lines that will contribute significantly to the understanding of T cell biology as a very important research model as well as an important livestock species. The generated animals reveal the function of different T cell populations in chickens and will help to better understand the role of these cells during the interaction with various pathogens in birds.
MetaGut: Insights into gut microbiomes in stem cell transplantation by comprehensive shotgun long-read sequencing
Authors: Spohr Philipp , Scharf Sebastian , Rommerskirchen Anna , Henrich Birgit , Jäger Paul , Klau Gunnar W. , Haas Rainer , Dilthey Alexander , Pfeffer Klaus 
Published: March 2023

AbstractThe gut microbiome is a diverse ecosystem, dominated by bacteria; however, fungi, phages/viruses, archaea, and protozoa are also important members of the gut microbiota. Up to recently, exploration of taxonomic compositions beyond bacteria as well as an understanding of the interaction between the bacteriome with the other members was limited due to 16S rDNA sequencing. Here, we developed MetaGut, a method enabling the simultaneous interrogation of the gut microbiome (bacteriome, mycobiome, archaeome, eukaryome, DNA virome) and of antibiotic resistance genes based on optimized long-read shotgun metagenomics protocols and custom bioinformatics. Using MetaGut we investigated the longitudinal composition of the gut microbiome in an exploratory clinical study in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT; n = 31). Pre-transplantation microbiomes exhibited a 3-cluster structure, associated withBacteroides/Phocaeicola, mixed composition andEnterococcusabundances. MetaGut revealed substantial inter-individual and temporal variabilities of microbial domain compositions, human DNA, and antibiotic resistance genes during the course of alloHSCT. Interestingly, viruses and fungi accounted for substantial proportions of microbiome content in individual samples (up to >50% and >20%, respectively). After leukopenia, strains were stable or newly acquired. Our results demonstrate the disruptive effect of alloHSCT on the gut microbiome and pave the way for future studies based on long-read metagenomics.
Signature reversion of three disease-associated gene signatures prioritizes cancer drug repurposing candidates
Authors: Fisher Jennifer L. , Wilk Elizabeth J. , Oza Vishal H. , Howton Timothy C. , Flanary Victoria , Clark Amanda D. , Hjelmeland Anita B. , Lasseigne Brittany N. 
Published: March 2023

SummaryDrug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug perturbations most inversely related to the disease-associated gene signature to identify drugs that may reverse that signature. We assessed the performance and biological relevance of three approaches for constructing disease-associated gene signatures (i.e, limma, DESeq2, and MultiPLIER) and prioritized the resulting drug repurposing candidates for four low-survival human cancers. Our results were enriched for candidates that had been used in clinical trials or performed well in the PRISM drug screen. Additionally, we found that pamidronate and nimodipine, drugs predicted to be efficacious against the brain tumor glioblastoma (GBM), inhibited the growth of a GBM cell line and cells isolated from a patient derived xenograft (PDX). Our results demonstrate that by applying multiple disease-associated gene signature methods, we prioritized several drug repurposing candidates for low-survival cancers.Graphical Abstract
Leukemic stem cells hijack lineage inappropriate signalling pathways to promote their growth
Authors: Kellaway Sophie G , Potluri Sandeep , Keane Peter , Blair Helen J. , Chin Paulynn S , Ptasinska Anetta , Worker Alice , Ames Luke , Adamo Assunta , Coleman Daniel JL , Khan Naeem , Assi Salam A. , Krippner-Heidenreich Anja , Raghavan Manoj , Cockerill Peter N , Heidenreich Olaf , Bonifer Constanze 
Published: March 2023

SummaryAcute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re- grow remain unknown. Here, we examined the well characterised t(8;21) AML sub-type as a model to address this question. Using a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.
Loss of daylength sensitivity by splice site mutation in Cannabis
Authors: Leckie Keegan M. , Sawler Jason , Kapos Paul , Mackenzie John O. , Giles Ingrid , Baynes Katherine , Lo Jessica , Celedon Jose M , Baute Gregory J. 
Published: March 2023

AbstractAdaptations to high latitude photoperiods have been under positive selection during the domestication of many short-day (SD) flowering crops. Photoperiod insensitivity (auto-flowering) in drug-typeCannabis sativacircumvents the need for SD flowering requirements making outdoor cultivation in high latitudes possible. However, the benefits of photoperiod insensitivity are counterbalanced by low cannabinoid contents and poor flower quality in auto-flowering genotypes. Despite recent legalization in some countries, a mechanistic understanding of photoperiod insensitivity in cannabis is still lacking. Herein, we identify a splice site mutation withinPSEUDO-RESPONSE REGULATOR 37 (CsPRR37) in auto-flowering cannabis that causes photoperiod insensitivity. Using a combination of GWAS, fine mapping, and gene expression analyses, our results strongly indicateCsPRR37as the most likely candidate for causing photoperiod insensitivity. Research into the pervasiveness of this mutation and others effecting flowering time will help elucidate its domestication history and advance cannabis breeding towards a more sustainable outdoor cultivation system.
Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation
Authors: Ayagama Thamali , Charles Philip D , Bose Samuel J , Boland Barry , Priestman David A , Aston Daniel , Berridge Georgina , Fisher Roman , Cribbs Adam P , Song Qianqian , Mirams Gary R , Heather Lisa , Galione Antony , Herring Neil , Schotten Ulrich , Capel Rebecca A , Platt Frances M , Platt Frances M , Krame Holger , Verheule Sander , Burton Rebecca AB 
Published: March 2023

SummaryEndolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL help facilitate elimination of damaged membrane and cytosolic proteins, protein aggregates, membranous organelles and also play an important role in calcium signalling. Despite the importance of EL, their specific role in cardiovascular disease is not well understood. In particular, it’s unclear how EL contribute to atrial pathology over longer time frames. To shed light on this question, we conducted a comprehensive analysis that involved proteomics, transcriptomics, integrated analysis, electron tomography, western blotting, and enzyme assays. To identify the role of EL in atrial fibrillation (AF), we applied a recently published organelle protein isolation method. We used this method to study biopsies from AF goat model and analyse the EL-specific proteins and pathways involved in this condition. Our results revealed the upregulation of the AMPK pathway and the expression of EL-specific proteins that were not found in whole tissue lysates (TL), including GAA, DYNLRB1, CLTB, SIRT3, CCT2, and muscle-specific HSPB2. We also observed structural anomalies, such as autophago-vacuole formation, irregularly shaped mitochondria, and glycogen deposition, which provide insights into the EL’s contribution to AF and related pathways and molecular mechanisms. Overall, our findings suggest that EL play an important role in the development of AF over longer time frames, and provide a more detailed understanding of the underlying molecular processes involved.