bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease
Authors: Awasthi Shivanshu , Grass G Daniel , Torres-Roca Javier , Johnstone Peter A S , Pow-Sang Julio , Dhillon Jasreman , Park Jong , Rounbehler Robert J , Davicioni Elai , Hakansson Alex , Liu Yang , Fink Angelina K , DeRenzis Amanda , Creed Jordan H , Poch Michael , Li Roger , Manley Brandon , Fernandez Daniel , Naghavi Arash , Gage Kenneth , Lu-Yao Grace , Katsoulakis Evangelia , Burri Ryan J , Leone Andrew , Ercole Cesar E , Palmer Joshua D , Vapiwala Neha , Deville Curtiland , Rebbeck Timothy R , Dicker Adam P , Kelly William , Yamoah Kosj 
Published: August 2022

Abstract

Background
Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.

Methods
This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non–African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score.

Results
The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non–African American men). A higher proportion of African American men with National Comprehensive Cancer Network–classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non–African American men. Self-identified African American men were twice more likely than non–African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes.

Conclusions
Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.
Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Rodriguez Cristina P , Kang Hyunseok , Geiger Jessica L , Burtness Barbara , Chung Christine H , Pickering Curtis R , Fakhry Carole , Le Quynh Thu , Yom Sue S , Galloway Thomas J , Golemis Erica , Li Alice , Shoop Jeffrey , Wong Stuart , Mehra Ranee , Skinner Heath , Saba Nabil F , Flores Elsa R , Myers Jeffrey N , Ford James M , Karchin Rachel , Ferris Robert L , Kunos Charles , Lynn Jean M , Malik Shakun 
Published: August 2022

Abstract
TP53 mutation is the most frequent genetic event in head and neck squamous cell carcinoma (HNSCC), found in more than 80% of patients with human papillomavirus–negative disease. As mutations in the TP53 gene are associated with worse outcomes in HNSCC, novel therapeutic approaches are needed for patients with TP53-mutated tumors. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issues of identifying and developing clinical trials for patients with TP53 mutations. Subcommittees, or breakout groups, were tasked with developing clinical studies in both the locally advanced and recurrent and/or metastatic (R/M) disease settings as well as considering signal-seeking trial designs. A fourth breakout group was focused on identifying and standardizing biomarker integration into trial design; this information was provided to the other breakout groups prior to the meeting to aid in study development. A total of 4 concepts were prioritized to move forward for further development and implementation. This article summarizes the proceedings of the Clinical Trials Planning Meeting with the goal of developing clinical trials for patients with TP53-mutant HNSCC that can be conducted within the National Clinical Trials Network.
Inadvertent retention of Descemet membrane after penetrating keratoplasty for pseudophakic bullous keratopathy
Authors: Ontiveros-Holguín Alejandro , Pacheco-Padrón Jorge 
Published: August 2022

Abstract
A retained Descemet membrane pertains to a type of retrocorneal membrane—a well-known yet rare complication of penetrating keratoplasty. We present a case of retained Descemet membrane after penetrating keratoplasty for pseudophakic bullous keratopathy. A 71-year-old woman presented to the ophthalmology clinic for loss of visual acuity. The previous year she had undergone phacoemulsification on both eyes, resulting in pseudophakic bullous keratopathy in the right eye; an uneventful penetrating keratoplasty was performed on the affected eye. The following day at follow-up, an undulated retrocorneal membrane was discovered on slit-lamp examination: corresponding to a retained Descemet membrane. A satisfactory descemetorhexis was performed. Timely diagnosis and intervention allowed for a remarkable outcome, with a best-corrected visual acuity of 20/50 OD with contact lens use.
Molecular fraction in the Galactic Centre: The Central Molecular and H i Zones
Authors: Sofue Yoshiaki 
Published: August 2022

ABSTRACT
By mapping the molecular fraction of the Galactic Centre (GC), we quantitatively address the question of how much molecular and central the CMZ (central molecular zone) is. For this purpose, we analyse the CO and H i-line archival data, and determine the column- (surface-) and volume-molecular fractions, $f_{\rm mol}^\Sigma$ and $f_{\rm mol}^\rho$, which are the ratio of column-mass density of H2 projected on the sky to that of total gas (H2 + H i) from the line intensities, and the ratio of volume-mass densities of H2 to total gas from the brightness temperature, respectively. It is shown that $f_{\rm mol}^\Sigma$ is as high as ∼0.9–0.95 in the CMZ, and $f_{\rm mol}^\rho$ is 0.93–0.98 in the GC Arms I and II attaining the highest value of ∼0.98 toward Sgr B2. The expanding molecular ring (EMR, or the parallelogram) has a slightly smaller $f_{\rm mol}^\rho$ as ∼0.9–0.93. We define the CMZ as the region with $f_{\rm mol}^\Sigma \ge 0.8\rm {-\!\!-}0.9$ between the shoulders of plateau-like distribution of H2 column density from l = −1${_{.}^{\circ}}$1 to +1${_{.}^{\circ}}$8 having Gaussian vertical distribution with a half thickness of ±0${_{.}^{\circ}}$2. The CMZ is embedded in the Central H i Zone (CHZ), which is defined as an H i disc between l ∼ −2° and +2${_{.}^{\circ}}$5, b = −0${_{.}^{\circ}}$5 and +0${_{.}^{\circ}}$5. Based on the analysis, we discuss the origin of CMZ and interstellar physics such as the volume filling factors of molecular and H i gases inferred from the difference between $f_{\rm mol}^\Sigma$ and $f_{\rm mol}^\rho$.
Unveiling the disc structure in ultraluminous X-ray source NGC 55 ULX-1
Authors: Barra F , Pinto C , Walton D J , Kosec P , D’Aì A , Di Salvo T , Del Santo M , Earnshaw H , Fabian A C , Fuerst F , Marino A , Pintore F , Robba A , Roberts T P 
Published: August 2022

ABSTRACT
Ultraluminous X-ray sources (ULXs) are the most extreme among X-ray binaries in which the compact object, a neutron star or a black hole, accretes matter from the companion star, and exceeds a luminosity of $10^{39} \ \rm erg \, s^{-1}$ in the X-ray energy band alone. Despite two decades of studies, it is still not clear whether ULX spectral transitions are due to stochastic variability in the wind or variations in the accretion rate or in the source geometry. The compact object is also unknown for most ULXs. In order to place constraints on to such scenarios and on the structure of the accretion disc, we studied the temporal evolution of the spectral components of the variable source NGC 55 ULX-1. Using recent and archival data obtained with the XMM-Newton satellite, we modelled the spectra with two blackbody components which we interpret as thermal emission from the inner accretion flow and the regions around or beyond the spherization radius. The luminosity–temperature (L–T) relation of each spectral component agrees with the L ∝ T4 relationship expected from a thin disc model, which suggests that the accretion rate is close to the Eddington limit. However, there are some small deviations at the highest luminosities, possibly due to an expansion of the disc and a contribution from the wind at higher accretion rates. Assuming that such deviations are due to the crossing of the Eddington or supercritical accretion rate, we estimate a compact object mass of 6–14 M⊙, favouring a stellar-mass black hole as the accretor.
ipaQTL-atlas: an atlas of intronic polyadenylation quantitative trait loci across human tissues
Authors: Ma Xuelian , Cheng Shumin , Ding Ruofan , Zhao Zhaozhao , Zou XuDong , Guang Shouhong , Wang Qixuan , Jing Huan , Yu Chen , Ni Ting , Li Lei 
Published: August 2022

Abstract
Functional interpretation of disease-associated non-coding variants remains a significant challenge in the post-GWAS era. Our recent study has identified 3′UTR alternative polyadenylation (APA) quantitative trait loci (3′aQTLs) and connects APA events with QTLs as a major driver of human traits and diseases. Besides 3′UTR, APA events can also occur in intron regions, and increasing evidence has connected intronic polyadenylation with disease risk. However, systematic investigation of the roles of intronic polyadenylation in human diseases remained challenging due to the lack of a comprehensive database across a variety of human tissues. Here, we developed ipaQTL-atlas (http://bioinfo.szbl.ac.cn/ipaQTL) as the first comprehensive portal for intronic polyadenylation. The ipaQTL-atlas is based on the analysis of 15 170 RNA-seq data from 838 individuals across 49 Genotype-Tissue Expression (GTEx v8) tissues and contains ∼0.98 million SNPs associated with intronic APA events. It provides an interface for ipaQTLs search, genome browser, boxplots, and data download, as well as the visualization of GWAS and ipaQTL colocalization results. ipaQTL-atlas provides a one-stop portal to access intronic polyadenylation information and could significantly advance the discovery of APA-associated disease susceptibility genes.
Small-molecule activators specific to adenine base editors through blocking the canonical TGF-β pathway
Authors: Yang Yudong , Zhang Chi , Song Yixuan , Li Yawen , Li Pingping , Huang Min , Meng Feilong , Zhang Mingliang 
Published: August 2022

Abstract
Adenine base editors (ABEs) catalyze A-to-G conversions, offering therapeutic options to treat the major class of human pathogenic single nucleotide polymorphisms (SNPs). However, robust and precise editing at diverse genome loci remains challenging. Here, using high-throughput chemical screening, we identified and validated SB505124, a selective ALK5 inhibitor, as an ABE activator. Treating cells with SB505124 enhanced on-target editing at multiple genome loci, including epigenetically refractory regions, and showed little effect on off-target conversion on the genome. Furthermore, SB505124 facilitated the editing of disease-associated genes in vitro and in vivo. Intriguingly, SB505124 served as a specific activator by selectively promoting ABE activity. Mechanistically, SB505124 promotes ABE editing, at least in part, by enhancing ABE expression and modulating DNA repair-associated genes. Our findings reveal the role of the canonical transforming growth factor-β pathway in gene editing and equip ABEs with precise chemical control.
Association between kinetic of anti-neutrophil cytoplasmic antibody (ANCA), renal survival and relapse risk in ANCA glomerulonephritis
Authors: Samoreau Clément , Piccoli Giorgina Barbara , Martin Cécile , Gatault Philippe , Vinatier Emeline , Bridoux Frank , Riou Jérémie , Desouche Alice , Jourdain Pierre , Coindre Jean-Philippe , Wacrenier Samuel , Guibert Fanny , Henry Nicolas , Blanchet Odile , Croué Anne , Djema Assia , Pouteau Lise-Marie , Copin Marie-Christine , Beauvillain Céline , Subra Jean-François , Augusto Jean-François , Brilland Benoit 
Published: August 2022

ABSTRACT

Background
Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes.

Methods
This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)].

Results
Over a follow-up of 56 months [interquartile range (IQR) 34–101], a median of 19 (IQR 13–25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P = .019) and tended to have a lower renal survival (P = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78–31.4), P = .008]).

Conclusion
ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease.
An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer
Authors: Mathews Cara , Lorusso Domenica , Coleman Robert L , Boklage Susan , Garside Jamie 
Published: August 2022

Abstract

Background
There is no clear standard of care for advanced/recurrent endometrial cancer (EC) following platinum-based therapy. Dostarlimab is approved for patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent EC. This indirect treatment comparison (ITC) assessed dostarlimab efficacy and safety from the single-arm GARNET (NCT02715284) trial compared with doxorubicin from ZoptEC (NCT01767155).

Patients and Methods
Patient-level data and study variables from GARNET Cohort A1 (dMMR/MSI-H EC) and the ZoptEC doxorubicin control arm were merged. Patients were matched based on eligibility criteria (main analysis population). Safety population included all patients who received treatment. The primary efficacy comparison outcome, overall survival (OS), was calculated using a Cox proportional hazards model, with adjusted stabilized inverse probability of treatment weighting. Modified assessment-scheduled matching Kaplan--Meier analysis was used for progression-free survival (PFS) and time to deterioration (TTD) in quality of life (QoL).

Results
In the main analysis population, median (95% CI) OS was not reached (NR; 18.0 months--NR) for dostarlimab (n = 92) and was 11.2 (10.0-13.1) months for doxorubicin (n = 233; HR: 0.41 [95% CI: 0.28-0.61]); median PFS was 12.2 (3.3-NR) and 4.9 (4.1-6.6) months, respectively. Median TTD in QoL was NR (2.5-NR; n = 61) and 4.5 (4.1-5.4; n = 188) months, respectively. Similar rates of adverse events (AEs, 11.6% vs 15.3%) and serious AEs (34.1% vs 30.1%) were observed with dostarlimab (n = 129) and doxorubicin (n = 249). Grade ≥3 AEs occurred in 48.1% vs 78.3%, respectively.

Conclusion
This ITC suggests a favorable benefit:risk profile for dostarlimab in patients with dMMR/MSI-H advanced/recurrent EC.
A Queen, a Reformer, and Weavers
Authors: Podany Amanda H. 
Published: August 2022

AbstractThis chapter focuses largely on the biography of the Early Dynastic queen Baranamtara of Lagash, who oversaw a large estate belonging to the House of Women (E-Mi), as attested by hundreds of administrative tablets from its archive. Her husband, king Lugalanda, administered his own estate, but his archive has not been found. Baranamtara conducted her own diplomacy through envoys, exchanged gifts with queens of other lands, offered sacrifices at religious festivals, and traveled around the city-state to appease the gods. Like the kings, Baranamtara was represented by a statue in the temple, and her statue received offerings after her death. Her funeral was attended by hundreds of mourners, and she was provided with lavish gifts for the afterlife. The king of Lagash at the time of her death was Urukagina, whose biography continues the chapter. He presented himself as a reformer, rooting out corruption and caring for orphans and widows. During his reign, the E-Mi palace (supervised by queen Shasha) increased its production of textiles, also increasing the number of textile workers. Three female supervisors of textile workers in the E-Mi—Zum, Igi-bar, and Emete—are the focus of the final biography in this chapter. Administrative texts can be used to follow their careers for a few years, and to compare their wages with those of their male counterparts. Textiles had become an important item of trade in southern Mesopotamia and women were largely responsible for their production.
Princesses and Musicians
Authors: Podany Amanda H. 
Published: August 2022

AbstractShamshi-Adad (1807–1776), a king with obscure origins, took control of the city of Ekallatum in northern Mesopotamia and from there built an empire encompassing much of modern Syria and northern Iraq, a region dominated by Amorite tribes. He constructed a new capital city at Shubat-Enlil and appointed his sons Ishme-Dagan and Yasmah-Addu to be viceroys in the cities of Ekallatum and Mari respectively. A case study of diplomatic marriage explores the marriage of Yasmah-Addu to princess Beltum of Qatna. This includes the negotiations, gifts between families, dowry, the choice of Beltum’s chambers at Mari, and the continued presence of her childhood nanny. The chapter describes the many quarters within the palace, which was renowned in its time. After the death of Shamshi-Adad, local king Zimri-Lim took control of Mari. The chapter provides a biography of a musician there, Bazatum, and of Rishiya, the chief musician. Music was central to Mesopotamian life and was regarded as essential for the gods. An overview is given of types of instruments, musical training, and performances, including a ritual for the goddess Ninigizibara, a deified lyre. As a girl, Bazatum lived in the Mari palace, in the women’s quarters. Sickness was a concern for palace residents like her; ill people were separated from others. Bazatum later married a high official and moved to his country estate where she supervised a weaving workshop. Shortly thereafter, the palace of Mari burned down and Zimri-Lim’s reign ended.
Empire Builders, Sculptors, and Deportees
Authors: Podany Amanda H. 
Published: August 2022

AbstractIn the eleventh and tenth centuries bce, small kingdoms dominated the Near East and writing was not used much. Three peoples had a large influence on later cultures: the Arameans, whose language spread across the Near East; the Phoenicians, who developed an alphabet that was adopted widely; and the Israelites, who are first attested in sources outside the Bible during this era. In the late tenth century, Neo-Assyrian kings began the creation of a huge empire. Ashurnasirpal II was a militaristic ruler who boasted of his conquests, and moved the capital city to Kalhu, which was populated with people from across the empire. The walls of his palace were decorated with stone relief sculptures showing the king’s achievements. The sculptors’ stages of creating the reliefs are reconstructed, including consultation with the king, religious considerations of what to depict, quarrying the stone blocks, and carving and painting the images once the blocks were in place. Many scenes depicted sieges and other military encounters. Deported people are profiled based on their depictions in sculptures from the reigns of several kings. Later, Sargon II moved the Assyrian capital to Dur-Sharrukin and built another palace, also with relief sculptures. Sargon II conquered Samaria in Israel, along with many Levantine cities, and deported tens of thousands of people. His son Sennacherib built another new capital, again with a new palace and more sculptures. He focused one room on the siege of Lachish in Judah; these also provide details about the logistics of deportation.
Gardeners, Artisans, and a Centenarian Priestess
Authors: Podany Amanda H. 
Published: August 2022

AbstractThis chapter includes some political history of the late Neo-Assyrian empire and the Neo-Babylonian empire, along with profiles of workers who helped maintain the economy and society of these states. Politically, the chapter includes a short biography of Ashurbanipal, including his literacy; his library; his conflicts with Elam, Babylonia, and the Arabs; his rivalry and wars against his brother, king Shamash-shumu-ukin of Babylon; and his victory in those wars. It also discusses the reasons for the collapse of the Neo-Assyrian empire; Nebuchadnezzar II’s program to rebuild Babylon, his conquests of Judah in 597 and 587 bce, and the deportation of Judeans to Babylon. Their king Jehoiakin was provided with rations by the Babylonian palace. Profiles of workers include a Se’-idri, a gardener in Harran, whose family grew grapes for wine. The life expectancy, family size, and diet of gardeners are discussed. Weavers, goldsmiths, washermen, and perfume-makers provided products and services to elites in both Assyria and Babylon; their products, expertise, pay, and working conditions are detailed. Running through the chapter are events in the life of Adad-guppi, a priestess of the moon god from Harran who lived to be 102 years old, and whose son, Nabonidus, eventually became king of Babylon. She longed for the Sin temple in Harran to be rebuilt after it was destroyed in 609, and dedicated her life to this cause. Both she and Nabonidus believed that he became king because Sin had willed it. When she died, she received an elaborate funeral.