bluuebunny/crossref_metadata_2025 huggingface dataset:
Proton acceleration from picosecond-laser interaction with a hydrocarbon target
Authors: YANG Yuchen , HUANG Taiwu , JIANG Ke , YU Mingyang , ZHOU Cangtao
Published: August 2022

As an intense picosecond laser pulse irradiates a hydrocarbon target, the protons therein can be accelerated by the radiation pressure as well as the sheath field behind the target. We investigate the effect of the laser and hydrocarbon target parameters on proton acceleration with two/three-dimensional particle-in-cell simulations. It is found that the resulting two-ion species plasma can generate a multiple peaked charge-separation field that accelerates the protons. In particular, a smaller carbon-to-hydrogen ratio, as well as the thinner and/or lower density of the target, leads to a larger sheath field and thus proton beams with a larger cutoff energy and smoother energy spectrum. These results may be useful in achieving high-flux quasi-monoenergetic proton beams by properly designing the hydrocarbon target.
Experimental studies of cusp stabilization in Keda Mirror with AXisymmetricity (KMAX)
Authors: LI Qing , ZHU Guanghui , REN Baoming , YING Jiacheng , YANG Zhida , SUN Xuan
Published: August 2022

Stabilization of the axisymmetric magnetic mirror relies on the pressure-weighted magnetic field curvature. We report a new experiment by configuring a magnetic cusp structure to stabilize m = 1 interchange mode in the KMAX tandem mirror. The cusp configuration is formed by reversing currents in the two side cell coils, and a stronger cusp can lead to a more stable plasma once the null point of the cusp is less than 35–40 cm away from the device axis. The density fluctuations measured by four axial Langmuir probes are mitigated by 70%–80%. The stabilization effect is consistent with the prediction of a theoretical calculation.
Elementary symmetric polynomials and martingales for Heckman-Opdam processes
Authors: Rösler Margit , Voit Michael
Published: August 2022

We consider the generators

L
k

L_k

of Heckman-Opdam diffusion processes in the compact and non-compact case in

N
N

dimensions for root systems of type

A
A

and

B
B

, with a multiplicity function of the form

k
=
κ

k
0

k=\kappa k_0

with some fixed value

k
0

k_0

and a varying constant

κ
∈

[
0
,
∞
[

\kappa \in \,[0,\infty [

. Using elementary symmetric functions, we present polynomials which are simultaneous eigenfunctions of the

L
k

L_k

for all

κ
∈

]
0
,
∞
[

\kappa \in \,]0,\infty [

. This leads to martingales associated with the Heckman-Opdam diffusions

(

X

t
,
1

,
…
,

X

t
,
N

)

t
≥
0

(X_{t,1},\ldots ,X_{t,N})_{t\ge 0}

. As our results extend to the freezing case

κ
=
∞

\kappa =\infty

with a deterministic limit after some renormalization, we find formulas for the expectations

E

(

∏

j
=
1

N

(
y
−

X

t
,
j

)
)
,

\mathbb E(\prod _{j=1}^N(y-X_{t,j})),

y
∈

C

y\in \mathbb C

.
MARVEL domain containing CMTM4 affects CXCR4 trafficking
Authors: Bona Alexandra , Seifert Michael , Thünauer Roland , Zodel Kyra , Frew Ian J. , Römer Winfried , Walz Gerd , Yakulov Toma A.
Published: August 2022

Defective zebrafish cmtm4 slowed the development of the posterior lateral line (pLL) by altering the Cxcr4b gradient across the pLL primordium (pLLP). Analysis in mammalian cells uncovered that CMTM4 interacted with CXCR4 and altered its glycosylation pattern but did not affect internalization or degradation of CXCR4.
IgIDivA: immunoglobulin intraclonal diversification analysis
Authors: Zaragoza-Infante Laura , Junet Valentin , Pechlivanis Nikos , Fragkouli Styliani-Christina , Amprachamian Serovpe , Koletsa Triantafyllia , Chatzidimitriou Anastasia , Papaioannou Maria , Stamatopoulos Kostas , Agathangelidis Andreas , Psomopoulos Fotis
Published: August 2022

Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio.tools/igidiva
Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry
Authors: Schmieder Roland E , Mahfoud Felix , Mancia Giuseppe , Narkiewicz Krzysztof , Ruilope Luis , Hutton David W , Cao Khoa N , Hettrick Douglas A , Fahy Martin , Schlaich Markus P , Böhm Michael , Pietzsch Jan B
Published: August 2022

Aims

Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach.

Methods and results

The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and −14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from −11.0–−21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses.

Conclusion

Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.
Differences in epiphytic trunk communities in secondary forests and plantations of southern Ecuador
Authors: Fernández-Prado Noelia , Aragón Gregorio , Prieto María , Benítez Ángel , Martínez Isabel
Published: August 2022

Deforestation is the most important cause of biodiversity loss in tropical ecosystems. Epiphytic species, lichens and bryophytes, are very sensitive to environmental changes, including those produced by conversion of primary forests into secondary vegetation. However, little is known about the differences between different secondary forests and plantations regarding the epiphytic biota. We compared epiphytic communities among different secondary forests and non-native plantations in southern Ecuador. Four forest types were considered: non-native Pinus patula plantations, monospecific secondary forests of Alnus acuminata, monospecific secondary forests of Andesanthus lepidotus and mixed secondary forests. Within each forest type, two stands were surveyed, establishing a total of 80 plots and analyzing four trees per plot. We estimated lichen and bryophyte cover in four inventories per tree and calculated and compared different metrics for taxonomic and functional diversity, as well as community composition. The results revealed forest type as the major predictor for the species and functional traits richness, and for diversity and composition. In total, 422 taxa were identified (312 lichens and 110 bryophytes), with mixed secondary forests having the richest communities (194 species) and non-native plantations having the lowest richness (105 species). Bryophyte richness was highest in A. lepidotus forests. Taxonomic and functional diversity, and species composition differed greatly among forest types and followed a different pattern depending on the organism considered. Lichens were the most sensitive indicators of environmental conditions associated with different tropical forest types.
An analysis of the steepest descent method to efficiently compute the three-dimensional acoustic single-layer operator in the high-frequency regime
Authors: Gasperini D , Beise H- P , Schroeder U , Antoine X , Geuzaine C
Published: August 2022

Using the Cauchy integral theorem, we develop the application of the steepest descent method to efficiently compute the three-dimensional acoustic single-layer integral operator for large wave numbers. Explicit formulas for the splitting points are derived in the one-dimensional case to build suitable complex integration paths. The construction of admissible steepest descent paths is next investigated and some of their properties are stated. Based on these theoretical results, we derive the quadrature scheme of the oscillatory integrals first in dimension one and then extend the methodology to three-dimensional planar triangles. Numerical simulations are finally reported to illustrate the accuracy and efficiency of the proposed approach.
Not So Dangerous? Nationalism and Foreign Policy Preference
Authors: Ko Jiyoung
Published: August 2022

In the field of international relations, it has long been believed that nationalism generates adverse foreign policy preferences. This article revisits this long-standing assumption by investigating how stimulating nationalistic sentiments shapes mass foreign policy preferences in two contexts, namely when celebrating national achievements and greatness with a focus on the national Self and when invoking negative historical memories in relation to a salient Other. Using a survey experiment conducted in China, which capitalized on visual stimuli drawn from real-world sources to stoke respondents’ nationalistic sentiments, this article shows that not all rises of nationalism are the same. Adverse foreign policy preferences, such as a preference for a hawkish approach, an uncompromising attitude, and a dislike for the status quo, emerge when nationalistic sentiments are stoked by invoking negative historical memories but not by celebrating general national achievements and greatness.
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

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

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

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

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

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

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

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

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

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

This 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

Shamshi-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

In 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

This 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.
Great God A'Mighty! The Dixie Hummingbirds
Authors: Zolten Jerry
Published: August 2022

Great God A’Mighty follows the career of the venerated and influential Dixie Hummingbirds from their origins in the 1920s segregated South to postwar successes that carried over well into the twenty-first century. In Greenville, South Carolina, James Davis organized a group to sing in school and at church. Aspiring professionals, they, as the Dixie Hummingbirds, embarked on a campaign of “wildcatting,” working local radio and communities to build a fanbase. Their breakthrough came in 1939 with fourteen sides released on the Decca label. With the addition of lead singer Ira Tucker, the Hummingbirds forged ahead, making Philadelphia their base and touring the East Coast as far south as Florida. During World War II, the Hummingbirds performed at New York City’s integrated nightclub Café Society, where they perfected harmonies and stagecraft. Following the war, the Hummingbirds experimented. Recording for several independent labels, they eventually signed with Peacock Records and, with the addition of electric guitarist Howard Carroll, released a string of trendsetting soul gospel hits that put them on top. The quintessential lineup was Ira Tucker, James Walker, James Davis, Beachey Thompson, William Bobo, and Howard Carroll. Collaborating with Paul Simon and Stevie Wonder, the Hummingbirds broke into the mainstream in the 1970s. Their continued successes well into the twenty-first century garnered them an international following and standing as a revered institution. Mentored by the late Ira Tucker, the current lineup of the Dixie Hummingbirds is forging ahead to keep the ninety-plus-year legacy alive.
“A Wheel in a Wheel, ’Way Up in the Middle of the Air”
Authors: Zolten Jerry
Published: August 2022

James Davis, founding member of the Dixie Hummingbirds, came of age in 1920s segregated Greenville, South Carolina. The African American community nonetheless thrived there with its own institutions, businesses, schools, churches, and entertainment. Blacks and whites lived in proximity but interacted rarely and out of necessity. Davis was close to his mother, Jannie, a devoutly religious homemaker. His father, John, was constantly on the move, hustling a living as best he could. His father taught him to sing using shape notes, where the shape of a note, not its position on a staff, indicated pitch. Davis attended the all-black Sterling High School, where he and friend Barney Parks with encouragement and training from teachers organized an acapella quartet to sing at high school programs and local churches. In 1928, the group traveled to Atlanta, where at the annual Church of God in Christ Convention they performed for the first time for an audience outside their own community. Billed as the Sterling High School Quartet, they were applauded and as a self-perceived sensation set out in a borrowed car to seek their fortune as professional gospel quartet singers.
The Theogony and the Works and Days
Authors: Sattler Barbara M.
Published: August 2022

This chapter shows Hesiod’s work as the beginning of central discussions in the area of natural philosophy, ethics, and political philosophy and as the first attempt in Western literature to account systematically for the different phenomena in the universe. It is demonstrated that Hesiod is the first to offer a general account of time and space: space is shown as a necessary condition for anything to come into being; time is depicted as cyclical in connection with the natural year and as linear in the progress of the divine generations and in the decline in human history. Hesiod’s Works and Days is discussed as the first attempt to sketch the big structures of human history, which is seen a story of moral decline. Finally, Hesiod’s suggestions for how to act rightly in corrupt times and how to account for normativity in terms of the natural world are investigated.
Hōnen’s Senchaku-Shū
Authors: Inukai Yumiko
Published: August 2022

This chapter explores Hōnen’s teachings of the nembutsu presented in the Senchaku Hongan Nembutsu Shū, a doctrinal text of the Pure Land Buddhism founded in Japan in the twelfth century ce. It is shown how intriguing and astute Hōnen is, especially with regard to his sole endorsement of the nembutsu and his insight into its psychological implications. It is argued particularly that his teachings of the nembutsu are informed by his own spiritual journey of profound self-reflection and self-realization, and he consequently places much weight on the psychological process of the nembutsu practice in which the practitioner’s sense of the self becomes transformed to the point where she “forgets herself.” It aims to show the authenticity of the Senchaku-Shū, as it represents personal experiences and awareness of what it is to be a human, written by someone who indeed underwent very common aspects of human life—failure and disappointment.
B. R. Ambedkar on “Castes in India: Their Mechanism, Genesis and Development”
Authors: Krishnamurthy Meena
Published: August 2022

In “Castes in India,” Ambedkar gives a pathbreaking account of the origin and evolution of caste in India. This chapter begins by explaining what caste is and why it originated, in Ambedkar’s view, and by discussing the role that caste plays in the oppression of women in India. The author argues that, in giving a causal explanation of women’s oppression, Ambedkar departs from other important political works of the time, including Gandhi’s, which all but ignore the oppression of women as an important form of social inequality. The author discusses the philosophical lessons that can be learned from reading Ambedkar’s essay. Drawing on Charles W. Mills’s criticisms of liberal political theory, the author closes the chapter by arguing that, because of the insights it offers, Ambedkar’s “Castes in India” serves as an important corrective to the traditional canon in political philosophy.
Ethics in Place and Time
Authors: Guerrero Alexander
Published: August 2022

This chapter introduces the Ahnishinahbӕótjibway philosopher Wub-e-ke-niew’s classic book, We Have the Right to Exist: A Translation of Aboriginal Indigenous Thought. Wub-e-ke-niew presents a distinct philosophical worldview and way of life, that of the Ahnishinahbӕótjibway, and contrasts it with what he calls the Lislakh (Western, Euro-American) perspective. This chapter concentrates on two central philosophical themes that emerge: (1) the contrast between Lislakh and Ahnishinahbӕótjibway conceptions of time; and (2) the related differences between Lislakh and Ahnishinahbӕótjibway conceptions of ethical life. In doing so, it suggests that the Ahnishinahbӕótjibway ethical view articulated by Wub-e-ke-niew can help illuminate and support possible responses to the “cluelessness” objection to consequentialist ethical theories, in addition to grounding a principled environmentalist perspective.
Peggy Glanville-Hicks, Sinfonia da Pacifica (1952–53)
Authors: Rogers Victoria
Published: August 2022

This chapter explores the theoretical, structural, and stylistic characteristics of Peggy Glanville-Hicks’s melody-rhythm structure, locating it within the context of twentieth-century composition and the dilemmas that had beset Western art music following the collapse of tonality at the turn of the twentieth century. Glanville-Hicks’s writings form the backdrop to the chapter, elucidating the why and the what of the melody-rhythm concept and providing a springboard for the case study that forms the core of the chapter: an analysis of the third movement of her Sinfonia da Pacifica (1952–53). This analysis is in turn the catalyst for the final part of the chapter, which offers an evaluation of the melody-rhythm structure and asks whether it proved to be more avant-garde or postmodern in its essential nature.
William James: A Study in Human Nature
Authors: Yaden David B. , Newberg Andrew B.
Published: August 2022

According to William James, to understand a person’s beliefs, then seek to learn more about that person’s temperament and life circumstances. Thus, this chapter focuses on the story of William James’s life and his influences to understand how he developed the worldview that he brought to The Varieties of Religious Experience. James’s life was in many ways a study in contrasts. He became a scientist, but trained first as an artist; he was a skeptic, but was fascinated by spiritual feelings; he hoped to understand mental states in terms of physiology, but he defended the inherent value of individual subjectivity; he taught physiology for years but always argued against simplistic reductionism. This familiarity with seeming contradictions may have enabled James to feel comfortable examining religious experience from a scientific perspective—an approach there is still much to learn from.
Revelatory Experiences
Authors: Yaden David B. , Newberg Andrew B.
Published: August 2022

The founders of most of the world’s major religions and innumerable other prophets, seers, and sages through the ages have described hearing voices––Joan of Arc, to name just one well-known example among many, both heard and saw angels. Yet nowadays most people would be alarmed if a loved one told them that they were “hearing voices” or “having visions” that other people cannot hear or see. In popular parlance, these phrases are almost synonymous with serious mental illness. But this is precisely what occurs during revelatory experiences, or voices, visions, or epiphanies that seem to come from a source beyond the self. This chapter describes these experiences and considers the question: Given that so many venerated historical figures heard voices, how can this be squared with the modern assumption of psychopathology?
Paranormal Experiences
Authors: Yaden David B. , Newberg Andrew B.
Published: August 2022

The fields of psychology and neuroscience share an embarrassment about studying experiences involving spirits, heavenly entities, ghosts, and the like. Yet these experiences are reported surprisingly often and so should be studied scientifically to the extent that it’s possible. The focus of this chapter, paranormal experiences, involves such nonphysical entities. Paranormal experiences are somewhat unusual in that they are not associated with the same degree of positive outcomes as other spiritual experiences, although that may have to do with the difficult circumstances in which they frequently occur.
Beliefs Reprise
Authors: Yaden David B. , Newberg Andrew B.
Published: August 2022

Throughout this book, following James, the focus has been on the causes, correlates, and consequences of spiritual experiences, trying to set aside the question of whether they are “real” in the metaphysical sense. But how should the kind of knowledge about the nature of reality that sometimes seems to come from these spiritual experiences be treated? This chapter reviews the responses of three prominent philosophers: William James, Bertrand Russell, and Ludwig Wittgenstein. For Wittgenstein, one can accept such experiences but must stay silent regarding the question of their reality. For Russell, a person can acknowledge and appreciate the psychological value of the experiences, but should treat any apparent knowledge from the experience regarding supernatural content as delusional. James makes a distinction between his professional conclusions and his personal conclusions. Professionally, he believes that one simply cannot know whether a spiritual experience points to any further supernatural reality. But personally, James claims that one can make a leap of faith by adopting a belief that spiritual experiences point to a supernatural reality due to their overall good effects. This chapter comments on and provides additional context to these various possible philosophical responses.
Conclusion
Authors: Yaden David B. , Newberg Andrew B.
Published: August 2022

In James’s discarded first draft of The Varieties, the opening line read: “There is something in life, as one feels its presence, that seems to defy all possible resources of phraseology.” The supposed ineffability of spiritual experiences has been widely discussed, and some have suggested that it is impossible to understand these experiences unless you have had one. Yet it has been shown that quite a bit can be said about spiritual experiences, and that they can indeed be studied scientifically in a number of different ways. As seen throughout this book, scientific progress in the 21st century on better understanding these profound experiences can and has been made. This concluding chapter discusses how on-going work will likely bring still more scientific advances in understanding spiritual experiences, and an even better understanding of life’s most mysterious moments can be looked forward to in the future.