THE ROLE OF INTRAOPERATIVE FROZEN SECTION OF SENTINEL LYMPH NODES IN UPFRONT BREAST CONSERVATION CANCER SURGERY

Objective: Sentinel lymph node biopsy is the standard of care in clinically negative axilla in breast cancer patients for which frozen section (FS) is routinely performed intraoperatively. The objective of this study was to justify the use of FS in terms of number of tests performed and their impact on decision-making and cost saving. Materials and Methods: We retrospectively reviewed our prospectively maintained data from January 2014 to January 2018 for intraoperative FS in upfront breast conservation surgery patients. Results: A total of 357 patients were studied. All were female. Median age was 50 years (24–84). Mean tumour size was 29.11 mm. Numbers of sentinel lymph nodes identified were 1 in 50 (14.2%) patients, 2 in 121 (33.89%) patients and ≥3 in 186 (52%) patients. Number of positive sentinel lymph nodes was 0 in 264 (73.9%) patients, 1 in 62 (17.4%) patients, 2 in 20 (5.6%) patients and ≥3 in 11 (3.08%) patients. Axillary lymph node dissection (ALND) was offered to 30 (8.4%) patients as per the American College of Surgeons Oncology Group Z0011. The results for ALND showed that only 8 (2.3%) out of 30 patients had positive nodes identified in the additional axillary nodes dissected. Sensitivity of FS was 97% and specificity was 98.86%. False-negative rate was 3.22%. Conclusion: Intraoperative FS can be safely omitted in early breast cancer patients undergoing upfront breast conservation cancer surgery due to high sensitivity and specificity leading to low false-negative rates. ALND can be performed as a second operation as warranted only in a minority of patients. Key words: American College of Surgeons Oncology Group Z0011 trial, axillary lymph node dissection, intraoperative frozen section, sentinel lymph node biops

Limited Evidence for Parallel Evolution Among Desert-Adapted Peromyscus Deer Mice

Warming climate and increasing desertification urge the identification of genes involved in heat and dehydration tolerance to better inform and target biodiversity conservation efforts. Comparisons among extant desert-adapted species can highlight parallel or convergent patterns of genome evolution through the identification of shared signatures of selection. We generate a chromosome-level genome assembly for the canyon mouse (Peromyscus crinitus) and test for a signature of parallel evolution by comparing signatures of selective sweeps across population-level genomic resequencing data from another congeneric desert specialist (Peromyscus eremicus) and a widely distributed habitat generalist (Peromyscus maniculatus), that may be locally adapted to arid conditions. We identify few shared candidate loci involved in desert adaptation and do not find support for a shared pattern of parallel evolution. Instead, we hypothesize divergent molecular mechanisms of desert adaptation among deer mice, potentially tied to species-specific historical demography, which may limit or enhance adaptation. We identify a number of candidate loci experiencing selective sweeps in the P. crinitus genome that are implicated in osmoregulation (Trypsin, Prostasin) and metabolic tuning (Kallikrein, eIF2-alpha kinase GCN2, APPL1/2), which may be important for accommodating hot and dry environmental conditions

Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freunds Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.The Higher Education Commission (HEC) of Pakistan (under the SRGP funding No. 357SRGP/HEC/2014) supported the study only financially and was not involved in the designing of the project. The authors are grateful to the National Research Foundation of Korea (NRF), Seoul National University, grant funded by the Korean Government (MSIP) (No. 2009–0083533). The Proff: Yeong Shik Kim (National Research Foundation of Korea (NRF), Seoul National University) was actively involved in the designing of the experiment and analysis of the results

Chromosome-length genome assembly and structural variations of the primal Basenji dog (Canis lupus familiaris) genome

Background: Basenjis are considered an ancient dog breed of central African origins that still live and hunt with tribesmen in the African Congo. Nicknamed the barkless dog, Basenjis possess unique phylogeny, geographical origins and traits, making their genome structure of great interest. The increasing number of available canid reference genomes allows us to examine the impact the choice of reference genome makes with regard to reference genome quality and breed relatedness. Results: Here, we report two high quality de novo Basenji genome assemblies: a female, China (CanFam_Bas), and a male, Wags. We conduct pairwise comparisons and report structural variations between assembled genomes of three dog breeds: Basenji (CanFam_Bas), Boxer (CanFam3.1) and German Shepherd Dog (GSD) (CanFam_GSD). CanFam_Bas is superior to CanFam3.1 in terms of genome contiguity and comparable overall to the high quality CanFam_GSD assembly. By aligning short read data from 58 representative dog breeds to three reference genomes, we demonstrate how the choice of reference genome significantly impacts both read mapping and variant detection. Conclusions: The growing number of high-quality canid reference genomes means the choice of reference genome is an increasingly critical decision in subsequent canid variant analyses. The basal position of the Basenji makes it suitable for variant analysis for targeted applications of specific dog breeds. However, we believe more comprehensive analyses across the entire family of canids is more suited to a pangenome approach. Collectively this work highlights the importance the choice of reference genome makes in all variation studies

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR

Sexuality and secrecy in the medieval Arabic romance of Majnun Layla

This dissertation demonstrates how secrecy is intricately linked with sexuality in the medieval Arabic romance of Majnun Layla, and other \u27Udhri love stories as recorded in the tenth-century Kitab al-Aghani. It argues that in the \u27Udhri romances, specifically the romance of Majnun Layla, we see how medieval Arabic literature valued and assigned importance to what may be termed a dialectic of secrecy and revelation in the organization of sexuality. Although critics have discussed the theme of \u27love\u27s revelation\u27 in Majnun Layla, it is uniquely the contribution of this dissertation to have elucidated the multiple paradoxes associated with this theme, especially as they pertain to depictions of chastity, courtship, and marriage in the stories. Among the most important paradoxes linked with this theme of love\u27s revelation is that love or desire, in these medieval romances, is defined as both suppression and expression. This paradox, the conception of desire as both concealment and disclosure, has significant implications for understanding conflicts in models of chastity, courtship, and marriage as represented in these romances. This dissertation examines the rendering of these conflicts, and suggests that they may be better understood in terms of tensions between literary portrayals of old and new models of courtship and marriage

Sexuality and secrecy in the medieval Arabic romance of Majnun Layla

This dissertation demonstrates how secrecy is intricately linked with sexuality in the medieval Arabic romance of Majnun Layla, and other \u27Udhri love stories as recorded in the tenth-century Kitab al-Aghani. It argues that in the \u27Udhri romances, specifically the romance of Majnun Layla, we see how medieval Arabic literature valued and assigned importance to what may be termed a dialectic of secrecy and revelation in the organization of sexuality. Although critics have discussed the theme of \u27love\u27s revelation\u27 in Majnun Layla, it is uniquely the contribution of this dissertation to have elucidated the multiple paradoxes associated with this theme, especially as they pertain to depictions of chastity, courtship, and marriage in the stories. Among the most important paradoxes linked with this theme of love\u27s revelation is that love or desire, in these medieval romances, is defined as both suppression and expression. This paradox, the conception of desire as both concealment and disclosure, has significant implications for understanding conflicts in models of chastity, courtship, and marriage as represented in these romances. This dissertation examines the rendering of these conflicts, and suggests that they may be better understood in terms of tensions between literary portrayals of old and new models of courtship and marriage