bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world study of medication-related osteonecrosis of the jaw from 2010 to 2023 based on Food and Drug Administration Adverse Event Reporting System
Authors: Zhong Yuhao , Dai Wei , Yin Lin , Wu Guomin , Wang Xiaoying 
Published: January 2025

Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a rare and severe adverse drug reaction (ADR) commonly seen in people taking drugs prescribed for metastatic cancer and osteoporosis. Prior studies only analyzed this ADR utilizing the public database Food and Drug Administration Adverse Event Reporting System (FAERS) by different stages (2010-2014, 2015-2021); a more comprehensive study is needed to analyze the MRONJ cases and the associated drugs from a longer time span. We conducted a retrospective pharmacovigilance analysis for all reported MRONJ cases between 2010 and 2023 in FAERS, using preferred terms and the primary suspect drug as searching conditions. Thus, this study aimed to analyze the MRONJ cases and the associated drugs more comprehensively. The reporting odds ratios (RORs) and 95% CIs were calculated for each queried drug. To distinguish the signal levels, we calculated the expected information component (EIC) and its 95% CI, using the Bayesian confidence propagation neural network (BCPNN) methods. We identified 22 846 MRONJ cases. A total of 15 drug classes including 30 suspect drugs showed different positive signal levels; among these drugs, 8, 5, and 17 had strong, medium, and weak intensity signals (+++, ++, and +), respectively. Drug classes involved bisphosphonate, RANKL inhibitor, radiotherapy drug, monoclonal antibody for cancer, corticosteroid, tyrosine kinase inhibitor, mammalian target of rapamycin inhibitor, aromatase inhibitor, cyclin-dependent kinase 4/6 inhibitor, immunomodulator, microtubule inhibitor, selective estrogen receptor modulator, sclerostin monoclonal antibody, estrogen receptor antagonist, and cytotoxic drug. Bisphosphonate, RANKL inhibitor, and radiotherapy drug exhibited higher risk than other classes with higher ROR or EIC 95% CI lower limit. Females had higher MRONJ incidence than males, and the mean age was 67.33 ± 11.71 yr. Compared with previous research, this study identified more drug classes and more novel medications with positive MRONJ signals that warrant further attention.
Circumstances of clinical fracture events with advancing age in older men
Authors: Ensrud Kristine E , Patel Sheena , Langsetmo Lisa , Cawthon Peggy M , Fink Howard A , Schousboe John T , Bauer Douglas C , Cauley Jane A , Orwoll Eric S ,   for the Osteoporotic Fractures in Men (MrOS) Study
Published: January 2025

Abstract
To characterize fracture circumstances by age at time of fracture among community-dwelling older men, we analyzed incident clinical fractures in the Osteoporotic Fractures in Men study. Participants were contacted every 4 mo to identify fractures confirmed by radiographic reports. Fractures were classified as fall- or non-fall-related and further categorized by degree of trauma: minimal (fall from ≤ standing height), moderate (fall on stairs, steps or curb), or severe (fall from &gt; standing height) for fall-related fractures; and minimal (eg, coughing), moderate (eg, collisions with objects during normal activity without falling), or severe (eg, motor vehicle accident) for non-fall-related fractures. Of 2351 clinical fractures in 1424 men during an average follow-up of 9.9 yr, 12.7% occurred at age &lt;75 yr, 15.7% at age 75-79 yr, 26.1% at age 80-84 yr, and 45.5% at age ≥85 yr. A total of 1891 fractures (80.4% of all fractures) were the result of a fall. The proportion of fall-related fractures steadily rose with increasing age at time of fracture, ranging from 65.8% in men &lt;75 yr rising to 84.7% in men ≥85 yr (p &lt; .001). Most fall-related fractures (76.4%) were due to minimal trauma; the proportion of all fractures due to a fall with minimal trauma steadily rose with increasing age (p &lt; .001). In contrast, approximately half of non-fall-related fractures (53.5%) were due to severe trauma. The proportion of all fractures due to severe trauma (whether fall-related or not) declined with advancing age (p &lt; .001). In conclusion, the most frequently occurring fracture circumstance in older men was a fall from ≤standing height. This circumstance was increasingly common with advancing age occurring in 7 of every 10 fractures in men ≥85 yr, while a fracture (fall-related or not) due to severe trauma was less common with advancing age. Findings have implications for development of fracture prevention strategies in older men.
Evaluation of optimal timing and therapeutic efficacy of radium-223 therapy for metastatic castration-resistant prostate cancer: a multicenter collaborative study
Authors: Urabe Fumihiko , Kadena Soshi , Tashiro Kojiro , Tokuoka Kenichi , Taneda Yuki , Fujiwara Kensuke , Goto Yuma , Nakano Juria , Kawano Shota , Iwamoto Yuya , Fukuokaya Wataru , Imai Yu , Iwatani Kosuke , Atsuta Mahito , Ito Kagenori , Yanagisawa Takafumi , Murakami Masaya , Tsuzuki Shunsuke , Yamamoto Toshihiro , Shimomura Tatsuya , Miki Jun , Kimura Takahiro ,   JIKEI-YAYOI Collaborative Group
Published: January 2025

Abstract

Background
Despite its demonstrated efficacy in prolonging overall survival (OS) and delaying skeletal-related events in the ALSYMPCA trial, the optimal timing of radium-223 initiation remains unclear. This study investigated factors influencing radium-223 treatment outcomes, including completion rates and survival.

Methods
This retrospective, multi-institutional study included 164 patients with metastatic castration-resistant prostate cancer (CRPC) who received radium-223 therapy. The primary endpoint was OS following radium-223 initiation. Secondary endpoints included factors associated with incomplete radium-223 treatment (&lt; six cycles) and poor OS. Multivariate Cox regression and multivariate logistic regression analyses were conducted to identify prognostic factors.

Results
The median OS times after CRPC diagnosis and radium-223 initiation were 39 and 12.5 months, respectively. Kaplan–Meier analysis showed that the OS of patients who completed six cycles of radium-223 treatment was longer than that of those who did not (18 vs. 5 months; P &lt; .001). Multivariate Cox analysis identified Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 1 (hazard ratio [HR] = 1.74, P = .046), PSA &gt; 17 ng/ml (HR = 2.93, P &lt; .001), and radium-223 incompletion (HR = 3.23, P &lt; .001) as independent predictors of poor OS. The radium-223 completion rate was 68.3%, and incompletion was significantly associated with prior docetaxel use (odds ratio [OR] = 5.97, P = .001), bone pain (OR = 2.64, P = .024), and PSA &gt; 17 ng/ml at the start of radium-223 treatment (OR = 3.12, P = .013).

Conclusions
Completion of all six cycles of radium-223 treatment were associated with favorable survival outcomes in metastatic CRPC patients. Prior docetaxel use, bone pain, and elevated PSA levels were significant risk factors for radium-223 incompletion. These findings suggest the importance of initiating radium-223 earlier in the treatment course for patients with favorable clinical profiles to maximize the therapeutic benefits.
Clinical outcomes and treatment patterns of maintenance avelumab in locally advanced or metastatic urothelial carcinoma: a multicenter collaborative study
Authors: Taneda Yuki , Urabe Fumihiko , Uchida Naoki , Kadena Soshi , Shibata Ken , Hashimoto Masaki , Kawano Shota , Takiguchi Yuki , Ohtsuka Takashi , Nakazono Minoru , Imai Yu , Iwatani Kosuke , Kayano Sotaro , Atsuta Mahito , Tashiro Kojiro , Murakami Masaya , Tsuzuki Shunsuke , Yamamoto Toshihiro , Yamada Hiroki , Miki Jun , Kimura Takahiro ,   JIKEI-YAYOI Collaborative Group
Published: January 2025

Abstract

Background
The JAVELIN Bladder 100 trial demonstrated improved overall survival (OS) with maintenance avelumab in patients with locally advanced or metastatic urothelial carcinoma UC (la/mUC) who achieved disease control following first-line platinum-based chemotherapy (1 L-PBC). However, real-world data on eligibility, utilization, and outcomes of maintenance avelumab therapy remain limited.

Methods
This retrospective study included patients with la/mUC who received 1 L-PBC. Eligibility for maintenance avelumab therapy was determined based on the best overall response to 1 L-PBC, with patients who achieved stable disease or a partial or complete response considered eligible. Survival outcomes were analyzed using the Kaplan–Meier method. Multivariate Cox regression analysis was used to identify prognostic factors among patients with la/mUC who received maintenance avelumab.

Results
Of 161 prospective patients, 67.1% were eligible for maintenance avelumab therapy, and 46.3% of eligible patients received the treatment. The median progression-free survival (PFS) following avelumab initiation was 10.2 months, whereas the median OS was not reached. Prognostic factors associated with PFS included the presence of liver metastases, elevated C-reactive protein (&gt; 1.0 g/dL), and administration of more than five cycles of 1 L-PBC. Adverse events occurred in 60% of patients treated with avelumab, with 16% experiencing grade 3–4 adverse events.

Conclusion
We emphasize the real-world applicability of maintenance avelumab for Japanese patients with la/mUC. Maintenance avelumab demonstrated favorable survival outcomes, consistent with clinical trial data. Identifying prognostic factors and optimizing treatment sequencing are essential strategies for improving outcomes in this patient population.
Increasing photosynthetic benefit with decreasing irrigation frequency in an Australian temperate pasture exposed to elevated carbon dioxide
Authors: Missen Melika L , De Kauwe Martin G , Hovenden Mark J 
Published: January 2025

Abstract
Elevated atmospheric CO2 (e[CO2]) often enhances plant photosynthesis and improves water status. However, the effects of e[CO2] vary significantly and are believed to be influenced by water availability. With a future warmer climate expected to increase the frequency and severity of extreme rainfall, the response of plants to e[CO2] under changing precipitation patterns remains uncertain. We examined the effects of e[CO2] and different irrigation regimes on perennial ryegrass in a free-air CO2 enrichment (FACE) experiment. Immediately after irrigation, the mean net photosynthetic rate was 21.2% higher under e[CO2] compared with ambient conditions. This benefit increased over time, reaching a 31.3% higher rate as days since watering increased, indicating a substantial increase in photosynthetic benefit with longer intervals between watering. Mean stomatal conductance was 21% lower in ryegrass under e[CO2] immediately after irrigation compared with ambient plots. However, the reduction in stomatal conductance under e[CO2] decreased as the interval between irrigation events increased, showing no difference 7–10 d after an irrigation event. These results imply that plants benefit most from carbon fertilization, assimilating relatively more carbon and losing less water, during periods with less frequent rainfall. These findings have significant implications for understanding leaf-level responses to climate change.
Rising from the ashes: evidence of old stellar populations and rejuvenation events in the very early Universe
Authors: Witten Callum , McClymont William , Laporte Nicolas , Roberts-Borsani Guido , Sijacki Debora , Tacchella Sandro , Simmonds Charlotte , Katz Harley , Ellis Richard S , Witstok Joris , Maiolino Roberto , Ji Xihan , Hayes Billy R , Looser Tobias J , D’Eugenio Francesco 
Published: January 2025

Abstract
While JWST has observed galaxies assembling as early as $z\sim 14$, evidence of galaxies with significant old stellar populations in the Epoch of Reionization (EoR) – the descendants of these earliest galaxies – are few and far between. Bursty star-formation histories (SFHs) have been invoked to explain the detectability of the earliest UV-bright galaxies, but also to interpret galaxies showing Balmer breaks without nebular emission lines. We present the first spectroscopic evidence of a $z\sim 7.9$ galaxy, A2744-YD4, which shows a Balmer break and emission lines, indicating the presence of both a mature and young stellar population. The spectrum of A2744-YD4 shows peculiar emission line ratios suggesting a relatively low ionization parameter and high gas-phase metallicity. A median stack of galaxies with similar emission line ratios reveals a clear Balmer break in their stacked spectrum. This suggests that a mature stellar population (∼80 Myr old) has produced a chemically enriched, disrupted interstellar medium. Based on SED-fitting and comparison to simulations, we conclude that the observed young stellar population is in fact the result of a rejuvenation event following a lull in star formation lasting ∼20 Myr, making A2744-YD4 and our stack the first spectroscopic confirmation of galaxies that have rejuvenated following a mini-quenched phase. These rejuvenating galaxies appear to be in an exceptional evolutionary moment where they can be identified. Our analysis shows that a young stellar population of just ∼30 per cent of the total stellar mass would erase the Balmer break. Hence, ‘outshining’ through bursty SFHs in early galaxies is likely plaguing attempts to measure their stellar ages and masses accurately.
The ESO SupJup Survey V: exploring atmospheric variability and orbit of the super-Jupiter AB Pictoris b with CRIRES+
Authors: Gandhi Siddharth , de Regt Sam , Snellen Ignas , Palma-Bifani Paulina , Abdoulwahab Idriss , Chauvin Gaël , Picos Darío González , Zhang Yapeng , Landman Rico , Stolker Tomas , Kesseli Aurora , Mulder Willeke , Chomez Antoine , Lagrange Anne-Marie , Zurlo Alice 
Published: January 2025

ABSTRACT
A growing number of directly-imaged companions have been recently characterized, with robust constraints on carbon-to-oxygen ratios and even isotopic ratios. Many companions and isolated targets have also shown spectral variability. In this work, we observed the super-Jupiter AB Pictoris b across four consecutive nights using VLT/CRIRES+ as part of the ESO SupJup survey, exploring how the constraints on chemical composition and temperature profile change over time using spectral line shape variations between nights. We performed atmospheric retrievals of the high-resolution observations and found broadly consistent results across all four nights, but there were differences for some parameters. We clearly detect H$_2$O, $^{12}$CO, and $^{13}$CO in each night, but abundances varied by ${\sim} 2\sigma$, which was correlated to the deep atmosphere temperature profiles. We also found differences in the $^{12}$C$/^{13}$C ratios in each night by up to ${\sim} 3\sigma$, which seemed to be correlated with the cloud deck pressure. Our combined retrieval simultaneously analysing all nights together constrained broadly the average of each night individually, with the C/O$=0.59\pm 0.01$, consistent with solar composition, and $^{12}$C$/^{13}$C $= 102\pm 8$, slightly higher than the Interstellar Medium (ISM) and Solar System values. We also find a low projected rotational velocity, suggesting that AB Pictoris b is either intrinsically a slow rotator due to its young age or that the spin axis is observed pole-on with a ${\sim} 90^\circ$ misalignment with its orbit inclination. Future observations will be able to further explore the variability and orbit of AB Pictoris b as well as for other companions.
Cleaning WASP-33 b transits from the host star photometric variability: analysis of TESS data from two sectors
Authors: Baluev Roman V , Sokov Eugene N 
Published: January 2025

ABSTRACT
Based on TESS observations of a $\delta$ Scuti variable WASP-33 obtained in 2019 and 2022, we thoroughly investigate the power spectrum of this target photometric flux and construct a statistically exhaustive model for its variability. This model contains 30 robustly justified harmonics detected in both the TESS sectors simultaneously, 13 less robust harmonics detected in a single TESS sector, a red noise, and a quasi-periodic noise term. This allowed us to greatly improve the accuracy of the exoplanet WASP-33 b transit timings, reducing the TTV residuals r.m.s. drastically, by a factor of 3.5, from 63 to 18 s. Finally, our analysis does not confirm existence of a detectable orbital phase variation claimed previously based on WASP-33 TESS photometry of 2019.
An analytic model of gravitational collapse induced by radiative cooling: instability scale, density profile, and mass infall rate
Authors: Gurian James , Liu Boyuan , Jeong Donghui , Hosokawa Takashi , Hirano Shingo , Yoshida Naoki 
Published: January 2025

ABSTRACT
We present an analytic description of the spherically symmetric gravitational collapse of radiatively cooling gas clouds, which illustrates the mechanism by which radiative cooling induces gravitational instability at a characteristic mass scale determined by the microphysics of the gas. The approach is based on developing the density–temperature relationship of the gas into a full dynamical model. We convert the density–temperature relationship into a barotropic equation of state, based on which we develop a refined instability criterion and calculate the density and velocity profiles of the gas. From these quantities, we determine the time-dependent mass infall rate on to the centre of the cloud. This approach distinguishes the rapid, quasi-equilibrium contraction of a cooling gas core to high central densities from the legitimate instability this contraction establishes in the envelope. We explicate the model in the context of a primordial mini-halo cooled by molecular hydrogen, and then provide two further examples: a delayed collapse with hydrogen deuteride cooling and the collapse of an atomic-cooling halo. In all three cases, we show that our results agree well with full hydrodynamical treatments.
Direct Measurement of the Mutation Rate and Its Evolutionary Consequences in a Critically Endangered Mollusk
Authors: Wooldridge T Brock , Ford Sarah M , Conwell Holland C , Hyde John , Harris Kelley , Shapiro Beth 
Published: January 2025

Abstract
The rate at which mutations arise is a fundamental parameter of biology. Despite progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much of Earth's biodiversity. Here, we present the first estimate of a germline mutation rate from the phylum Mollusca. We sequenced three pedigreed families of the white abalone Haliotis sorenseni, a long-lived, large-bodied, and critically endangered mollusk, and estimated a de novo mutation rate of 8.60 × 10−9 single nucleotide mutations per site per generation. This mutation rate is similar to rates measured in vertebrates with comparable generation times and longevity to abalone, and higher than mutation rates measured in faster-reproducing invertebrates. The spectrum of de novo mutations is also similar to that seen in vertebrate species, although an excess of rare C &gt; A polymorphisms in wild individuals suggests that a modifier allele or environmental exposure may have once increased C &gt; A mutation rates. We use our rate to infer baseline effective population sizes (Ne) across multiple Pacific abalone and find that abalone persisted over most of their evolutionary history as large and stable populations, in contrast to extreme fluctuations over recent history and small census sizes in the present day. We then use our mutation rate to infer the timing and pattern of evolution of the abalone genus Haliotis, which was previously unknown due to few fossil calibrations. Our findings are an important step toward understanding mutation rate evolution and they establish a key parameter for conservation and evolutionary genomics research in mollusks.
Franz Kafka
Authors: Liska Vivian , Balint Benjamin 
Published: January 2025

Franz Kafka (born 1883, Prague, Austria-Hungary [now in Czech Republic]—died 1924, Kierling, near Vienna, Austria) was a German-language writer whose works—most famously The Trial (Der Prozess, 1925) and Metamorphosis (Die Verwandlung, 1915)—gave us the twentieth century’s most imperishable fables about disorientation, guilt, and absurdity and, more generally, about the human condition in modernity. His writings, particularly his diaries and letters, also point to the complex ways “Western” Jews have negotiated between assimilation and tradition. The son of Julie Löwy and Hermann Kafka, Franz Kafka was born into a prosperous middle-class Jewish family. In his “Letter to the Father” (“Brief an den Vater,” 1919), Kafka blames his father for his alienation from his own Jewish heritage. “It was conceivable that we might have found each other in Judaism.” But the flimsy vestiges of Judaism passed on to him, Kafka writes, were “an insufficient scrap . . . a mere nothing, a joke—not even a joke. . . . It all dribbled away while you were passing it on” (Letter to his Father. New York: Schocken, 1966, p. 182). Kafka’s conflict with his father gets its fictional expression in his breakthrough story The Judgment (Das Urteil, 1913). Kafka did associate with German-Jewish intellectuals in Prague, including Max Brod, who would become Kafka’s promoter, literary executor, and first biographer. Kafka proved no less sensitive than Brod and his Zionist friends to the roiling anti-Semitism that would reach its horrific climax only after Kafka’s death. (Kafka’s three sisters were murdered in Nazi concentration camps.) Kafka witnessed firsthand the rising racism that accompanied the disintegration of the Habsburg Empire, including a three-day riot in Prague in December 1897. Yet Kafka did not take refuge in the embrace of Jewish belonging. “What have I in common with Jews?” he later remarked. “I have hardly anything in common with myself” (The Diaries of Franz Kafka. Translated by Ross Benjamin. New York: Schocken, 2023, p. 330). At age twenty-five, after earning a law degree at the University of Prague, Kafka was hired at the Workers’ Accident Insurance Institute. One of only two Jews among the 260 employees, he earned a reputation for diligence but found the office drudgery unbearable. He remained there until 1917, when he was diagnosed with tuberculosis. With considerable reluctance, Kafka published some fiction during his lifetime, including The Judgment, Metamorphosis, In the Penal Colony (In der Strafkolonie, 1919), and A Country Doctor (Ein Landarzt, 1919). A Hunger Artist (Ein Hungerkünstler, 1924) appeared shortly after his death. For the rest, we owe the survival of Kafka’s works to Brod’s disregard of Kafka’s instruction that his unpublished manuscripts be destroyed. After the Second World War, Brod edited a collected edition of Kafka’s works and letters (published in seven volumes by S. Fischer Verlag in 1976).