bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of deucravacitinib for genital, nail and scalp lesions in patients with psoriasis: a 24-week real-world study
Authors: Hagino Teppei , Onda Marina , Saeki Hidehisa , Fujimoto Eita , Kanda Naoko 
Published: August 2024

Abstract
Psoriasis is a chronic, complicated inflammatory skin disease. Genital, nail and scalp lesions with psoriasis are difficult to treat and can considerably impair patients’ quality of life (QoL). Deucravacitinib, an oral selective tyrosine kinase 2 inhibitor, may represent a novel therapeutic option that could improve these challenging manifestations. To investigate this, we conducted a retrospective study between January 2023 and February 2024, involving 70 patients with psoriasis treated with deucravacitinib 6 mg orally once daily for 24 weeks. We evaluated how many patients achieved a static Physician’s Global Assessment (PGA) of Genitalia (sPGA-GTM) score of clear/almost clear (0/1), PGA of Fingernail Psoriasis (PGA-F) 0/1, scalp-specific PGA (ss-PGA) 0/1, static PGA (sPGA) 0/1 and Dermatology Life Quality Index 0/1 at weeks 4, 16 and 24. We also assessed the Psoriasis Area and Severity Index scores. Deucravacitinib improved genital, nail and scalp lesions, as well as systemic eruption and QoL in patients with psoriasis. Deucravacitinib may be a promising treatment option for lesions in difficult-to-treat areas in patients with psoriasis.
Functional Transitions Among Older Adults in Rural China: Examining the Differential Roles of Care From Daughters’ and Sons’ Families
Authors: Zhao Pianpian , Zhang Yanan , Harper Sarah , Zeng Weihong , Li Shuzhuo 
Published: August 2024

Abstract

Objectives
Informal care provided by adult children is of great importance for older adults’ well-being in China. This paper investigates and compares the functional transitions among older adults living in rural areas who receive care from daughters’ and from sons’ families.

Methods
This study utilizes the “Well-being of Elderly Survey in Anhui Province” (WESAP) from 2001 to 2021. Our sample included 2,797 individuals aged 60 years or older. Functional status was based on the activities of daily living and the instrumental activities of daily living. We employed a random-effects ordered logit model to examine the functional transitions among the older adults.

Results
Receiving care from daughters’ families is significantly associated with a lower likelihood of functional decline compared to receiving care from sons’ families in rural China. The advantage associated with daughter care becomes more pronounced among older individuals with a severe functional difficulty compared to those with a mild or moderate functional difficulty. The difference is prevalent among older adults aged 75 and older, with less wealth or multiple chronic diseases, or who live alone. Furthermore, among those with severe functional difficulties, the daughter advantage is more significant for fathers as compared to mothers.

Discussion
Nowadays, daughters’ families can provide high-quality informal care, often surpassing that offered by sons’ families. This daughter advantage becomes even more significant among older adults who have a higher need for family care, such as those with severe disabilities and limited financial resources.
The role of heterogeneous stress in earthquake cycle models of the Hikurangi–Kermadec subduction zone
Authors: Liao Yi-Wun Mika , Fry Bill , Howell Andrew , Williams Charles A , Nicol Andrew , Rollins Chris 
Published: August 2024

SUMMARY
Seismic and tsunami hazard modelling and preparedness are challenged by uncertainties in the earthquake source process. Important parameters such as the recurrence interval of earthquakes of a given magnitude at a particular location, the probability of multifault rupture, earthquake clustering, rupture directivity and slip distribution are often poorly constrained. Physics-based earthquake simulators, such as RSQSim, offer a means of probing uncertainties in these parameters by generating long-term catalogues of earthquake ruptures on a system of known faults. The fault initial stress state in these simulations is typically prescribed as a single uniform value, which can promote characteristic earthquake behaviours and reduce variability in modelled events. Here, we test the role of spatial heterogeneity in the distribution of the initial stresses and frictional properties on earthquake cycle simulations. We focus on the Hikurangi–Kermadec subduction zone, which may produce Mw &gt; 9.0 earthquakes and likely poses a major hazard and risk to Aotearoa New Zealand. We explore RSQSim simulations of Hikurangi-Kermadec subduction earthquake cycles in which we vary the rate and state coefficients (a and b). The results are compared with the magnitude-frequency distribution (MFD) of the instrumental earthquake catalogue and with empirical slip scaling laws from global earthquakes. Our results suggest stress heterogeneity produces more realistic and less characteristic synthetic catalogues, making them particularly well suited for hazard and risk assessment. We further find that the initial stress effects are dominated by the initial effective normal stresses, since the normal stresses evolve more slowly than the shear stresses. A heterogeneous stress model with a constant pore-fluid pressure ratio and a constant state coefficient (b) of 0.003 produces the best fit to MFDs and empirical scaling laws, while the model with variable frictional properties produces the best fit to earthquake depth distribution and empirical scaling laws. This model is our preferred initial stress state and frictional property settings for earthquake modelling of the Hikurangi–Kermadec subduction interface. Introducing heterogeneity of other parameters within RSQSim (e.g. friction coefficient, reference slip rate, characteristic distance, initial state variable, etc.) could further improve the applicability of the synthetic earthquake catalogues to seismic hazard problems and form the focus of future research.
Lexical Language Contact Phenomena: A Combined Model Based on the Vocabulario español-guarani (18th century)
Authors: Gimeno María Cecilia , Stala Ewa 
Published: August 2024

Abstract
The purpose of this work, which falls within the areas of lexicography (studying missionary linguistics) and sociolinguistics (studying cultural contact), is to analyse the linguistic and cultural contacts between Spanish and Guarani, based on lexicographic material extracted from the Vocabulario español-guarani by Pablo Restivo (1728). The basis of the analysis is provided by the names of animals—one of the ‘secular’ fields where the highest frequency of borrowings is found (Cerno & Obermeier 2013). The methodology applied is the Haspelmath model (2009) and the Gruda model (2018). The premise is that the arrival and work of the Jesuit missionaries created cultural contact that is reflected in the codified language and, in turn, in this dictionary of the time. The main contribution is a new combined model of lexical reflections in a situation of cultural contact that can be applied in the analysis of this kind of lexicographic work, while an additional section provides a presentation of Restivo’s work and its background.
Modification of carbapenemase inhibition test and comparison of its performance with NG-Test CARBA 5 for detection of carbapenemase-producing Enterobacterales
Authors: Wang Yue , Huang Xiangning , Yin Dandan , Shen Siquan , Jian Cui , Sun Ziyong , Hu Fupin , Yu Hua , Chen Zhongju 
Published: August 2024

Abstract

Aims
Adequately and accurately identifying carbapenemase-producing Enterobacterales (CPE) is vital for selecting appropriate antimicrobial therapy and implementing effective infection control measures. This study aims to optimize the phenotypic detection method of carbapenemase for routine diagnostics in clinical microbiology laboratories.

Methods and Results
Carbapenemase genes in 2665 non-duplicate CRE clinical strains collected from various regions of China were confirmed through whole-genome sequencing (WGS). The carbapenemase inhibition test (CIT) was conducted and interpreted using different methods and breakpoints, then compared with the NG-Test CARBA 5 for carbapenemase detection. The diagnostic performance of the CIT method was optimal when the carbapenemase types were determined by comparing the inhibition zone diameters of the imipenem disc with 3-aminophenylboronic acid (APB) plus ethylenediaminetetraacetic acid (EDTA) to those of the imipenem disc with either APB or EDTA alone, with a breakpoint of 4 mm. The overall sensitivities of the current CIT, the modified CIT, and NG-Test CARBA 5 were 91.4%, 94.9%, and 99.9%, respectively. For detecting isolates co-producing Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs), the modified CIT method had higher sensitivity than the current method (70.0% vs. 53.3%), though this difference was not statistically significant (P = 0.063). The NG-Test CARBA 5 showed excellent performance for multi-carbapenemases diagnosis, with sensitivity and specificity of 97.1% and 100%, respectively.

Conclusions
Optimizing and standardizing the CIT method for clinical use is necessary. It has certain advantages in diagnosing multi-carbapenemase and rare carbapenemase production. However, for identifying common carbapenemase types, the NG-Test CARBA 5 demonstrated superior performance.
Effects of a liquid and dry Saccharomyces cerevisiae fermentation product feeding program on ruminal fermentation, total tract digestibility, and plasma metabolome of Holstein steers receiving a grain-based diet
Authors: Odunfa Oluwaseun A , Dhungana Anjan , Huang Zhengyan , Yoon Ilkyu , Jiang Yun 
Published: August 2024

Abstract
The study aimed to determine the effects of a postbiotic feeding program consisting of liquid and dry Saccharomyces cerevisiae fermentation product (SCFP) on ruminal fermentation, digestibility, and plasma metabolome of Holstein steers receiving a grain-based diet. Eight Holstein steers (body weight, BW, 467 ± 13.9 kg) equipped with rumen cannulas were used in a crossover design study, with 21 d per period and a 7-d washout period in between periods. Steers were stratified by initial BW and assigned to 1 of 2 treatments. The treatments were 1) Control, basal finishing diet only (CON); 2) SCFP, 1-d feeding of liquid SCFP (infused into the rumen via the cannula at 11 mL/100 kg BW) followed by daily feeding of dry SCFP (12 g/d, top-dressed). Feed and spot fecal samples were collected during days 17 to 20 for determination of digestibility and fecal excretion of N, P, Cu, and Zn. Digestibility was measured using acid-insoluble ash as an internal marker. Blood samples were collected on day 21 before the morning feeding. Rumen fluid samples were collected on days 0, 1, 2, 3, 5, and 21 via rumen cannula. Results were analyzed with the GLIMMIX procedure of SAS 9.4 (SAS, 2023). Treatment did not affect dry matter intake (P = 0.15) and digestibility (P ≥ 0.62). The fecal output and absorption of Zn, Cu, P, and N were not affected (P &gt; 0.22) by treatment. On day 1, the liquid SCFP supplementation tended to reduce (P = 0.07) ruminal VFA concentration and increased (P &lt; 0.01) the molar proportion of valerate. Feeding SCFP tended to increase total ruminal VFA on day 5 (P = 0.08) and significantly increased total VFA on day 21 (P = 0.05). Ruminal NH3–N was reduced (P = 0.02) on day 21 by supplementing SCFP. Treatment did not affect the production of proinflammatory cytokines, interleukin (IL)-1β (P &gt; 0.19), and IL-6 (P &gt; 0.12) in the whole blood in response to various toll-like receptor stimulants in vitro. Feeding SCFP enriched (P ≤ 0.05) plasma metabolic pathways, including citric acid cycle, pyrimidine metabolism, glycolysis/gluconeogenesis, retinol metabolism, and inositol phosphate metabolism pathways. In summary, supplementing liquid SCFP with subsequent dry SCFP enhanced ruminal total VFA production and reduced NH3–N concentration in the rumen. Furthermore, feeding SCFP enriched several important pathways in lipid, protein, and glucose metabolism, which may improve feed efficiency of energy and protein in Holstein steers.
Making the most of canopy light: shade avoidance under a fluctuating spectrum and irradiance
Authors: Sellaro Romina , Durand Maxime , Aphalo Pedro J , Casal Jorge J 
Published: August 2024

Abstract
In the field, plants face constantly changing light conditions caused by both atmospheric effects and neighbouring vegetation. This interplay creates a complex, fluctuating light environment within plant canopies. Shade-intolerant species rely on light cues from competitors to trigger shade avoidance responses, ensuring access to light for photosynthesis. While research often uses controlled growth chambers with steady light to study shade avoidance responses, the influence of light fluctuations in real-world settings remains unclear. This review examines the dynamic light environments found in woodlands, grasslands, and crops. We explore how plants respond to some fluctuations but not others, analyse the potential reasons for these differences, and discuss the possible molecular mechanisms regulating this sensitivity. We propose that studying shade avoidance responses under fluctuating light conditions offers a valuable tool to explore the intricate regulatory network behind them.
3D aeronomy of two mini-neptunes in the HD 63433 system and their in-transit absorption in Ly α and metastable He i lines
Authors: Berezutsky A G , Shaikhislamov I F , Rumenskikh M S , Miroshnichenko I B , Khodachenko M  L , Golubovskii M P , Sharipov S S 
Published: August 2024

ABSTRACT
The numerical simulation of the HD 63433 system is performed with the aim to study upper atmospheres of two mini-Neptunes, planets b and c, interacting with the stellar wind of the parent star. The obtained results demonstrate that both exoplanets form the extended envelopes with strong supersonic outflows. The synthetic absorption profiles in the Ly α line show that under moderate stellar wind conditions, similar to those of the normal solar wind, the energetic neutral atoms contribute to the absorption in the high-velocity blue wing of the line at a level of tens per cent. The absorption in metastable helium He i(23S) line appears rather weak and below the detection limit by current instruments. An important feature revealed by the simulations is that the tail of escaping atmospheric material of the inner planet disturbs the stellar wind at orbital location of the outer planet and might, therefore, affect its observation in Ly α line.
BSBM-11 NEUROCOGNITIVE OUTCOMES OF HIPPOCAMPUS-SPARING WHOLE-BRAIN RADIATION THERAPY VERSUS WHOLE-BRAIN RADIATION THERAPY IN PATIENTS WITH BRAIN METASTASIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Salman Afia , Naeem Unaiza , Ghazanfar Shamas , Jawed Areesha , Farooq Minaam 
Published: August 2024

Abstract

INTRODUCTION
Whole brain radiation therapy (WBRT) is administered both prophylactically and therapeutically in patients with suspected and confirmed brain metastasis. Despite effective intracerebral tumor control and reduction in neurological mortality, WBRT is associated with a substantial risk of cognitive decline. Hippocampus-sparing WBRT (HS-WBRT) allows for the preservation of memory and other cognitive functions. We aimed to evaluate the neurocognitive outcomes of HS-WBRT in comparison with WBRT in patients with brain metastases.

METHODS
We searched MEDLINE (PubMed), Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for cohort studies and clinical trials reporting on HS-WBRT compared to WBRT for neurocognitive outcomes in brain metastasis patients, from inception to March 2024. Studies that were published in non-English language(s) and/or did not report neurocognitive outcomes of HS-WBRT compared with WBRT were excluded. Summary data of the eligible studies was extracted, which was analyzed for neurocognitive function testing.

RESULTS
Of the total nine studies, seven were included in the quantitative analysis. HS-WBRT led to a statistically significant reduction in cognitive decline as measured by the Hopkins Verbal Learning Test (HVLT) raw scores for total recall (TR) [SMD = 0.34 [0.16,0.53]; I2= 65%; p = 0.0003], and delayed recall (DR) [SMD = 0.26 [0.13,0.39]; I2= 62%; p = 0.0001]. Cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), was also lower in the HS-WBRT group compared to the WBRT group [SMD = 0.82 [0.53,1.10]; I2= 88%; p &lt; 0.00001].

CONCLUSION
The findings of our study demonstrate that HS-WBRT confers a therapeutic advantage to WBRT in improving neurocognitive outcomes for patients with brain metastasis as measured by scores on HVLT-TR, HVLT-DR, and MoCA. Additional studies analyzing both treatment modalities’ adverse effects and mean survival time are imperative for informing future clinical recommendations.
BSLM-05 TRASTUZUMAB DERUXTECAN IN LEPTOMENINGEAL METASTASES FROM HER2-ALTERED CANCERS
Authors: Cao Toni , Roy-O’Reilly Meaghan , Yao Lilian , Ma Qian , Xu Nova , Nagpal Seema , Rogawski David 
Published: August 2024

Abstract
Emerging data suggest that trastuzumab deruxtecan (T-DXd) is a clinically active treatment for brain metastases from HER2+ breast cancer. We aimed to characterize the activity of T-DXd in the treatment of leptomeningeal metastases (LM) from a range of HER2-altered cancers. We reviewed neuro-oncology clinic records between July 2020 and December 2023 to identify patients who received T-DXd to treat LM. Out of 14 patients, 5 had HER2+ breast cancer, 5 had HER2-low breast cancer, 2 had HER2+ gastroesophageal cancer, and 2 had HER2-mutant non-small cell lung cancer. 8/14 (57%) patients had LM diagnosis confirmed with cancer cells in CSF found by cytology or circulating tumor cell (CTC) capture. 4/5 (80%) patients with HER2+ breast LM had a partial response on MRI using the EORTC/RANO-LM Revised-Scorecard. In contrast, 0/9 (0%) patients with other tumor pathologies had radiologic response of their LM to T-DXd. Median survival of the 5 patients with HER2+ breast cancer after initiating T-DXd was 13.9 months with 2 patients alive and continuing on T-DXd at data cutoff, whereas median survival of the 9 patients with other pathologies was 4.1 months (HR 0.32, 95% CI 0.097-1.0, p=0.05). Our findings agree with other retrospective studies showing clinical activity of T-DXd in HER2+ breast LM, but caution that T-DXd may be less effective in LM caused by HER2-low breast and other HER2-altered cancers. Given the small number of patients in our study, larger prospective studies are urgently needed to better delineate which LM patients benefit from T-DXd.
BSLM-09 IDENTIFICATION OF DRUGS WITH SELECTIVE ACTIVITY AGAINST MELANOMA-ASSOCIATED LEPTOMENINGEAL DISEASE USING PATIENT-DERIVED CIRCULATING TUMOR CELLS
Authors: Law Vincent , Bayle Simon , Duckett Derek , Forsyth Peter 
Published: August 2024

Abstract

BACKGROUND
Melanoma associated leptomeningeal disease (M-LMD) occurs in ~5% of late stage melanoma patients and the prognosis is dismal without effective treatments. The difficulty in obtaining enough patient-derived cerebral spinal fluid-circulating tumor cells (PD-CSF-CTCs) and the absence of model systems to study the biology of M-LMD have posed challenges in assessing novel therapeutics. To address this, we have made considerable progress in routinely collecting CSF and tissue specimens (in clinic and at rapid autopsy). Recently, we successfully propagated CSF-CTCs from patients in vitro and in murine xenograft models. With these tools and -omics techniques we found unique M-LMD-specific biological pathways. In the current preliminary study, we identified clinical compounds that could target these biological pathways and have efficacy against PD-CSF-CTCs in vitro and in vivo.

METHODS
PD-CSF-CTCs were derived and propagated from individual M-LMD patients. Next, a 384-well high throughput cell-based process was developed to screen a library of more than 1,400 FDA-approved small molecule compounds to identify pharmaceutics that inhibit cell proliferation. Clinical compounds with the highest sensitivity were selected for validation of efficacy in vivo via intrathecal (IT) delivery of patient-derived cell lines to establish M-LMD xenografts.

RESULTS
Of the 1,436 FDA-approved small molecule compounds, 57 (~3.9%) exerted 95% proliferation inhibition and 20 (~1.4%) had 100% killing effect in PD-CSF-CTCs and murine melanoma cell lines. The compounds with the highest sensitivity include ponatinib (EC50: 1.85 – 4.06e-06), sorafenib (EC50: 9.57 – 9.77e-06), ceritinib (EC50: 1.84 – 2.05e-06) and homoharringtonine (HHT) (3.63 – 4.11e-08). In a randomized murine M-LMD efficacy study, we selected the HHT compound which was given by systemic or intrathecal (IT) injections and found M-LMD mice that received a daily IT dose of 14.5ng HHT resulted prolonged median survival (control vs. HHT, P value: 0.0006; Mantel Cox test).

CONCLUSION
This is the first demonstration of an approach that allows for the rational development of therapeutics in M-LMD, which may help identify drug candidates for future trials.
BMRK-06 BRAIN METASTASIS FREE SURVIVAL OF HER2 LOW AND HER2 ZERO TRIPLE NEGATIVE METASTATIC BREAST CANCER: A WILMOT CANCER INSTITUTE EXPERIENCE (THE HERZELO-TNBC STUDY)
Authors: Evans William , Strawderman Myla , Zhang Huina , O’Regan Ruth , Hicks David , Dhakal Ajay 
Published: August 2024

Abstract

BACKGROUND
It is unclear if level of HER2 expression in metastasis triple negative breast cancer (mTNBC) affects risk of CNS metastasis (CNS-failure). Objective: to compare risk of CNS-failure between HER2-Low [immunohistochemistry 2+ (with ISH-negative) or 1+) and HER2-Zero (immunohistochemistry 0) mTNBC.

METHOD
This is a single-institution retrospective study of mTNBC diagnosed January 2010-January 2022. CNS metastasis at the time of mTNBC diagnosis were excluded. Overall survival (OS) and cause-specific risk of CNS-failure was described using Kaplan-Meier method stratified by HER2 status and compared using log-rank test. A multivariate Cox model was used to estimate hazard ratio (HR) for OS and cause-specific CNS-failure. Because death prior to CNS-failure is a competing-risk, cumulative incidence of CNS failure by HER2 status was estimated and compared using Gray’s test. To adjust for other covariates, Fine-Gray model was used to estimate sub-distribution hazard. Significance level for this study was 10%. HRs were reported with 90% confidence intervals (CI).

RESULTS
As of August 2023, 31 CNS-failures and 68 deaths were observed among 86 patients (57 HER2-Low, 29 HER2-Zero) enrolled. Baseline variables were similar in 2 groups except a higher proportion of bone metastasis in HER2-Low group (62% vs 42%, p=0.08). OS was not different between 2 groups in an unadjusted analysis [median(mo): HER2-Low=15.9 vs HER2-Zero =17.8, p=0.51], and in Cox model (HR=1.12, 90%CI=0.72-1.73, p=0.68). Cause-Specific analysis: HER2-Low group had shorter time to CNS-failure in unadjusted [median(mo): HER2-Low=22.0 vs HER2-Zero =33.4, p=0.082] and in Cox model (HR=2.29, 90%CI=1.20-4.37, p=0.035). Competing-Risk analysis: HER2-Low group had higher cumulative risk of CNS-failure in unadjusted analysis [median(mo): HER2-Low=34.5 vs HER2-Zero =not reached, p=0.049] and in Fine-Gray model (HR=2.69, 90%CI=1.42-5.12, p=0.011).

CONCLUSION
This single-institution study shows a higher risk of CNS-failure in HER2-Low compared to HER2-Zero mTNBC, even after accounting for death as competing risk.