Life Sciences Commons^™

Gene Signatures Derived From Transcriptomic-Causal Networks Stratify Colorectal Cancer Patients For Effective Targeted Therapy, Akram Yazdani, Heinz-Josef Lenz, Gianluigi Pillonetto, Raul Mendez-Giraldez, Azam Yazdani, Reza Hadi, Alan P Venook, Mark J Ratain, Naim Rashid, Benjamin G Vincent, Xueping Qu, Yujia Wen, Michael Kosorok, William F Symmans, John Paul Y C Shen, Michael S Lee, Scott Kopetz, Andrew B Nixon, Monica M Bertagnolli, Charles M Perou, Federico Innocenti

Faculty, Staff and Student Publications

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes. This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. The patients were enrolled in a randomized clinical trial receiving either cetuximab or bevacizumab in combination with chemotherapy. An external cohort of paired CRC normal and tumor …

Society For Immunotherapy Of Cancer: Updates And Best Practices For Multiplex Immunohistochemistry (Ihc) And Immunofluorescence (If) Image Analysis And Data Sharing, Janis M Taube, Joel C Sunshine, Michael Angelo, Guray Akturk, Margaret Eminizer, Cláudia S Ferreira, Benjamin Green, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Daniel Jiménez-Sánchez, Konstanty Korski, Ana Lako, Edwin R Parra, Marlon C Rebelatto, David L Rimm, Scott J Rodig, Jamie Rodriguez-Canales, Jeffrey S Roskes, Kurt A Schalper, Emanuel Schenck, Keith E Steele, Michael J Surace, Alexander S Szalay, Michael T Tetzlaff, Ignacio I Wistuba, Jennifer H Yearley, Carlo B Bifulco

Faculty, Staff and Student Publications

Objectives: Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force. The current effort represents a complementary manuscript for mIHC/IF analysis focused on the associated image analysis and data management.

Methods: The Society for Immunotherapy of Cancer convened a task …

Clinical And Imaging Features Of Head And Neck Metastasis Of High-Grade Glioma: A Single-Center Case Series, Rami W Eldaya, Diana Kaya, Michelle Williams, Susana Calle, Dawid Schellingerhout

Faculty, Staff and Student Publications

High-grade gliomas are the most frequent primary brain tumors, yet extraneural metastasis is exceedingly rare. This is in part secondary to the relatively poor survival of these patients and likely the shielding effect of the blood-brain barrier. Given the rarity of extraneural metastasis, the pathophysiology and imaging appearance of extraneural metastasis is under-reported and poorly understood. In this case series we present 6 patients with pathology-confirmed high-grade glioma and extraneural head and neck metastasis. We highlight imaging features of metastasis on CT, MRI, and PET/CT. We also explore potential correlations and pathophysiology of high-grade glioma metastasis to the head and …

Genetic Variations In Mdm2 Gene Contribute To Renal Cell Carcinoma Susceptibility: A Genotype–Phenotype Correlation Study, Shu-Yu Chang, Wen-Shin Chang, Hou-Yu Shih, Chao-Hsiang Chang, Hsi-Chin Wu, Yun-Chi Wang, Da-Tian Bau

Faculty, Staff and Student Publications

Background: This study aimed to investigate the polymorphic genotypes of MDM2 rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of MDM2 genotypes and environmental factors on RCC susceptibility.

Methods: A total of 135 RCC patients and 590 controls were recruited for MDM2 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients.

Results: MDM2 rs2279744, but not other polymorphisms, was significantly associated with an increased RCC risk (p = 0.0133). The MDM2 rs2279744 G allele was identified as …

Venetoclax-Based Combination Regimens In Acute Myeloid Leukemia, Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D Dinardo, Farhad Ravandi

Faculty, Staff and Student Publications

In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.

The Coins From The ‘Sleepy Spring’ At Safed (Ẓefat), Robert Kool

'Atiqot

Nine copper coins, eight of which were identified, were found in the Mamlūk–Ottoman-period building at Safed. The earliest specimen is a residual copper fals from the fifteenth century CE; the remaining specimens date to the late Ottoman period (second half of the nineteenth–twentieth centuries CE). The latest coin is a ‘Two Mils’ issued during the British Mandate of Palestine in 1942.

The Glass Finds From The ‘Sleepy Spring’ At Safed (Ẓefat), Natalya Katsnelson

'Atiqot

The excavation at Safed yielded a small assemblage of glass finds, including fragments of two beaker-shaped oil lamps, a small lid and two small cosmetic bottles of the Mamluk–Ottoman periods, as well as several beads, bracelets and glass vessels of the late Ottoman–British Mandate periods. This glass assemblage corresponds with the dating of the remains between the fifteenth and early twentieth centuries CE, comprising common locally produced artifacts of the Late Islamic period and items dating to the late Ottoman and British Mandate periods, some of which were imported.

A Mamluk-Period Mausoleum Near The ‘Sleepy Spring’ At Safed (Ẓefat), Hervé Barbé

'Atiqot

A trial excavation near the ‘Sleepy Spring’ fountain in Safed revealed the remains of a mausoleum, which was built during the late Mamluk period and remained in use until the early twentieth century. Three late Ottoman-period tombs found within the vaulted structure, and Ottoman-period cist tombs adjacent to the building, attest to the burial function of the site. No pre-Mamluk-period finds were uncovered at the site, indicating that the earliest occupation in this part of the ancient town was in the Mamluk period. Based on archaeological excavations and textual sources, urbanization of Safed was intensified during the Mamluk period, possibly …

The Faunal Remains From Ramla, Dana Shtainberg Finali, Ram Bouchnick

'Atiqot

The majority of the faunal remains from the excavation at Ramla were retrieved from Area A. The assemblage mostly comprises domestic livestock, including domestic fowl. It also includes a few remains of wild mammals, fish and songbirds. The very low numbers of pig bones at the site are characteristic of assemblages associated with cultures that imposed a taboo on eating pork, as Jewish and Muslim communities. The assemblage appears to represent refuse deposits, although their precise origin is unclear.

The Coins From Ramla, Robert Kool

'Atiqot

The excavation at Ramla yielded 39 coins, 19 of which were identified. More than half of the coins were dated to the Umayyad and Abbasid periods. Two silver fractions minted during the Fatimid period are noteworthy, attesting that the circulation of fractional silver and billon was more widespread than previously thought. Three Mamluk-period copper coins were also found.

Early Islamic-Period Metal Artifacts From Ramla, Ayala Lester

'Atiqot

Twenty-one metal objects, most of which are made of brass, were discovered in the excavation at Ramla, including household vessels and personal belongings. The metalware was predominantly retrieved from Area A Strata III–II, dated to the late Abbasid–Fatimid periods, attesting to the presence of metalworking professionals at Ramla in the Early Islamic period.

Early Islamic-Period Glass Finds From Ramla, Tamar Winter

'Atiqot

The excavation at Ramla yielded a rich variety of glass finds, most of which were free-blown and decorated, and some production remains. Some of the finds are characteristic of the Umayyad period, while most date to the Abbasid–Fatimid periods, with some types continuing into the Mamluk period. The rich variety of the glass assemblage and sophisticated nature of the vessel types attest to the affluence of the population inhabiting this part of Ramla, and the familiarity of this population with contemporary trends of the glass industry.

Provenance Study Of A Double-Stamped Jar Handle Of The Early Islamic Period From Ramla, Nitzan Amitai-Preiss, Anat Cohen-Weinberger

'Atiqot

A zir-jar handle found on the surface in Area B of the excavation in Ramla exhibited two stamps of identical design and orientation. It seems to have been produced in a workshop in the vicinity of Jerusalem (Nebi Samwil?) during the Early Islamic period.

Pottery And Stone Objects From The Abbasid–Fatimid Periods At Ramla, Hagit Torgë

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The pottery assemblage from the excavation at Ramla comprises well-known vessel types of the late Abbasid–Fatimid periods, mostly dating between the ninth and eleventh centuries CE. Most of the vessels were locally made; however, fine-ware vessels imported from as far as Egypt and China, were also found. Other probably imported items from Egypt are a Shabti figurine and a fragment of green marble. These luxury finds indicate that the area was most likely part of the affluent neighborhood of Ramla uncovered south of the White Mosque in the Early Islamic period.

Remains Of Buildings And Installations From The Late Abbasid–Fatimid And Mamluk Periods In Ramla, Ron Toueg, Hagit Torgë

'Atiqot

Salvage excavation carried out at Ramla revealed three strata in Area A (Strata III–I), comprising remains of buildings, installations, water cisterns, channels and cesspits ascribed to the late Abbasid–Fatimid periods (second half of the ninth to the end of the eleventh centuries CE). The latest occupation phase in Area A (Stratum I) was a short-term secondary use of Fatimid-period structures by inhabitants of the Mamluk period (thirteenth–sixteenth centuries CE). These remains were part of a previously exposed affluent neighborhood. The high economic status of the inhabitants of this area was further indicated by luxury finds, such as imported pottery vessels, …

Remains Of A Rural Settlement From The Late Hellenistic–Early Roman Periods And A Hiding Complex From The Roman Period At Ḥorbat Mazruq Near Abu Ghosh (With A Contribution By Donald T. Ariel), Daniel Ein-Mor

'Atiqot

Three areas were excavated at Ḥorbat Mazruq (A1–A3), revealing two structures with shafts in their courtyards leading to underground chambers, and a water reservoir that was incorporated into a subterranean hiding complex. Four burial caves were surveyed northwest of Area A1, only one was fully plotted; they probably served the residents of the site. The ceramic and numismatic finds date the architectural remains to the end of the second century BCE until the first century CE. The ceramic material found within the hiding complex, which canceled the original use of the installations at the site, is typical of the first …

Early Bronze Age Fauna From Tel Lod, Edward F. Maher Maher

'Atiqot

The excavations at Tel Lod yielded a small zooarchaeological assemblage, primarily dating to Early Bronze Age IB (Strata VII–IV); the material from the latest occupation (Strata III–II) dates to late EB IB or the EB IB/EB II transition. The fauna of both phases is dominated by domestic stock, comprising sheep, goats, cattle and pigs, which were used both for primary products, such as meat, and secondary products, such as dairy, wool, hair, traction and for breeding. Wild animals, such as boar, gazelle, deer and hare, were also occasionally exploited.

The Flint Assemblage From Tel Lod, Polina Spivak

'Atiqot

A total of 2258 flint items were unearthed during the excavation at Tel Lod, originating in five well-defined strata (VII–II) dated to EB IB and the EB IB/EB II transition. The assemblage comprises elements from two main flint industries: the Pottery Neolithic Lodian Culture and the Early Bronze Age Canaanean blade industry. The lithic assemblages from Tel Lod reflect the agricultural activities pursued by the inhabitants of this settlement during both the Late Neolithic and the Early Bronze periods.

Early Bronze Age Remains At Tel Lod, Amir Golani

'Atiqot

A rescue excavation conducted in the southwestern part of the Early Bronze Age mound at Lod exposed an intensive settlement. The architectural remains of Strata VI–IV demonstrate the use of rounded exterior corners for domestic structures, characteristic of the end of EB I and the transition into EB II. The architectural remains associated with Strata IV–III include large, possibly public buildings dating to the end of EB IB. The ceramic assemblages from Strata VII–II are typical of late EB I in central and southern Israel. Two Carbon-14 dates from Stratum IV indicate a date at the beginning of EB IB …

Early Bronze Age Ia Settlement Remains At Ḥorbat Ḥammim (South), Near Modi‘In, Edwin C.M. Van Den Brink, Liora Kolska Horwitz, Ofer Marder, Henk K. Mienis

'Atiqot

The excavation at Ḥorbat Ḥammim (South) yielded a rock-cut basin and a small cave within a limestone bedrock outcrop. The basin is similar to other rock-cut installations previously exposed in the area and dated to the Chalcolithic period.
The manmade rock-cut cave was entered through a shaft. The sediments from the shaft and the cave consisted of many potsherds, stone tools and animal bones, that may have been washed into the cave, or intentionally discarded in it. The cave may have been quarried as early as the Late Chalcolithic period, although the bulk of the pottery dates to EB IA, …

The Mollusks From Tel Bet Yeraḥ, Inbar Ktalav

'Atiqot

Bivalve remains retrieved from EB II–III Strata at Tel Bet Yeraḥ include specimens originating from the Sea of Galilee and from the Mediterranean Sea. The mollusks indicate the exploitation of nearby sources for food and raw material for fashioning decorative items, as well as long distance trade connections with the Mediterranean coastal region. A broken valve of Glycymeris nummaria, with an artificial perforation in the umbo, was probably collected on the shore and used as a pendant.

The Fauna From Tel Bet Yeraḥ, Miriam Pines

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A small assemblage of 20 bones was retrieved from Tel Bet Yeraḥ, the majority originating from EB III Strata III–I. Most of the bones belong to adult sheep/goat and cattle.

The Ground Stone Tools From Tel Bet Yeraḥ, Gil Haklay, Ianir Milevski

'Atiqot

A total of 19 ground stone artifacts were recovered from Tel Bet Yeraḥ. Nearly all were made of basalt, while some mortars and perforated stones were made of limestone; one item, a rubbing stone, was made of pumice. Although small, the ground stone tool assemblage conforms with previous observations at this EB II and III site.

The Flint Assemblage From Tel Bet Yeraḥ, Maayan Shemer

'Atiqot

The excavation at Tel Bet Yeraḥ yielded 209 flint items, originating from five distinct occupation strata. The assemblage generally represents an industry characteristic of the Early Bronze Age, defined mainly by the consistent presence of Canaanean blades. The abundance of Canaanean blades produced from local raw material may indicate the existence of a specialized workshop near the site.

A Ceramic Zoomorphic Figurine From Tel Bet Yeraḥ, Nadeshda B. Knudsen

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A well-made ceramic zoomorphic figurine was recovered from a domestic EB IB context (Stratum V) in the southern part of Tel Bet Yeraḥ. The physical characteristics of this figurine suggest that it was intended to represent an equid, possibly a donkey. Such animal figurines are common at Early Bronze Age sites, usually representing familiar domesticate animals. The purpose of these figurines remains obscure, with multiple suggestions offered, including their use as toys, talismans, teaching aids, exchange tokens, or for rituals.

Early Bronze Age Remains In The Southern Part Of Tel Bet Yeraḥ, Amir Golani

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Five strata were exposed during a salvage excavation near the southwestern fringes of Tel Bet Yeraḥ: late EB I (Stratum V), EB II (Stratum IV) and EB III (Strata III–I). The direct superposition of the strata suggests a minimal time interval between the occupations and a nearly continuous habitation. The architectural remains attest that this area was domestic in nature, a conclusion further supported by the small finds, which include a large quantity of holemouth vessels, probably used as cooking pots, fauna, flint, ground stones and mollusks. This part of the site appears to have been finally abandoned in EB …

Late Chalcolithic And Early Bronze Age Ia Settlement Remains At Kafr Kanna, Lower Galilee, Edwin C.M. Van Den Brink, Valentine Roux, Anastasia Shapiro, Maayan Shemer

'Atiqot

Four strata were distinguished at the site: Stratum 4, dating to the Late Chalcolithic period; Strata 3 and 2, to EB IA; and Stratum 1, sub-recent. The Late Chalcolithic remains consisted of a stone surface and an underlying fill, and the EB IA remains included wall segments of three structures: two buildings (Stratum 3) and a wall of a large double-apsed structure (Stratum 2). The technological analysis of the pottery from the site testifies to a transmission from the Late Chalcolithic to Early Bronze Age populations in the way of making utilitarian ceramics, indicating continuity of the same population. The …

Front Matter, The Editorial Board

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No abstract provided.

Key Virulence Factors Responsible For Differences In Pathogenicity Between Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine Sa14-14-2 And Its Pre-Attenuated Highly Virulent Parent Sa14, Byung-Hak Song, Sang-Im Yun, Joseph L. Goldhardt, Jiyoun Kim, Young-Min Lee

Animal, Dairy, and Veterinary Science Student Research

Japanese encephalitis virus (JEV), a neuroinvasive and neurovirulent orthoflavivirus, can be prevented in humans with the SA₁₄-14-2 vaccine, a live-attenuated version derived from the wild-type SA₁₄ strain. To determine the viral factors responsible for the differences in pathogenicity between SA₁₄ and SA₁₄-14-2, we initially established a reverse genetics system that includes a pair of full-length infectious cDNAs for both strains. Using this cDNA pair, we then systematically exchanged genomic regions between SA14 and SA₁₄-14-2 to generate 20 chimeric viruses and evaluated their replication capability in cell culture and their pathogenic potential in …

The Continuing Search For A Better Mouse Trap: Two Tests Of A Practical, Low-Cost Camera Trap For Detecting And Observing Small Mammals, Raymond D. Dueser, John H. Porter, Nancy D. Moncrief

Wildland Resources Faculty Publications

The advent of digital wildlife cameras has led to a dramatic increase in the use of camera traps for mammalian biodiversity surveys, ecological studies and occupancy analyses. For cryptic mammals such as mice and shrews, whose small sizes pose many challenges for unconstrained digital photography, use of camera traps remains relatively infrequent. Here we use a practical, low-cost small mammal camera platform (the “MouseCam”) that is easy and inexpensive to fabricate and deploy and requires little maintenance beyond camera service. We tested the MouseCam in two applications: a study of small mammal species composition on two transects across a barrier …