bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jesus vs Seth-Typhon: An Audience-Critical Approach to Mark 4:35–5:20
Authors: Lee Sanghwan 
Published: August 2024

Abstract
Scholars have approached the Gerasene Demoniac pericope (Mark 5:1–20; = GDP) in light of various traditions, such as the Homeric parallels, the Watcher (i.e. Enochic) story, the scapegoat motif, and imperial-critical and gendered perspectives. Without denying the validity of these attempts, I suggest that there is still an important—but largely ignored—set of traditions that deserves our attention: the Seth-Typhon traditions. Based on an audience-critical perspective, this article suggests that several elements in GDP could allude to the Seth-Typhon traditions in the minds of the Greco-Roman audience of Mark. The strength of this method is twofold. First, it accounts for the close relationship between GDP and its preceding pericope (i.e. the Storm-Stilling pericope; Mark 4:35–41). Second, it coherently explains multiple critical motifs—the crossing of the sea, the sleeping Jesus, the attempt to drown Jesus, the sea-storm, the foreign area, the legion of demons, and the death of the pigs—featured in Mark 4:35–5:20. According to this approach, Jesus in Mark 4:35–5:20 can be read as a divine warrior who outshines his pagan counterparts (i.e. Zeus and Osiris) as he battles against the cosmic forces of evil and eventually conquers them.
Disc novae: thermodynamics of gas-assisted binary black hole formation in AGN discs
Authors: Whitehead Henry , Rowan Connar , Boekholt Tjarda , Kocsis Bence 
Published: August 2024

ABSTRACT
We investigate the thermodynamics of close encounters between stellar mass black holes (BHs) in the gaseous discs of active galactic nuclei (AGNs), during which binary black holes (BBHs) may form. We consider a suite of 2D viscous hydrodynamical simulations within a shearing box prescription using the Eulerian grid code athena++. We study formation scenarios where the fluid is either an isothermal gas or an adiabatic mixture of gas and radiation in local thermal equilibrium. We include the effects of viscous and shock heating, as well as optically thick cooling. We co-evolve the embedded BHs with the gas, keeping track of the energetic dissipation and torquing of the BBH by gas and inertial forces. We find that compared to the isothermal case, the minidiscs formed around each BH are significantly hotter and more diffuse, though BBH formation is still efficient. We observe massive blast waves arising from collisions between the radiative minidiscs during both the initial close encounter and subsequent periapsis periods for successfully bound BBHs. These ‘disc novae’ have a profound effect, depleting the BBH Hill sphere of gas and injecting energy into the surrounding medium. In analysing the thermal emission from these events, we observe periodic peaks in local luminosity associated with close encounters/periapses, with emission peaking in the optical/near-infrared (IR). In the AGN outskirts, these outbursts can reach 4 per cent of the AGN luminosity in the IR band, with flares rising over 0.5–1 yr. Collisions in different disc regions, or when treated in 3D with magnetism, may produce more prominent flares.
Screening for familial disease presence in first-degree relatives of Behçet’s disease patients: Is measurement of common femoral vein wall thickness valuable for the diagnosis?
Authors: Boncukcuoğlu Ayşe Elif , Topal Erhan , Ergelen Rabia , Kaş Dilara , Alkan Elifnur , Kaya Gamzenur , Girgin Şevket , Ergun Tülin , Direskeneli Haner , Alibaz-Oner Fatma 
Published: August 2024

ABSTRACT

Objectives
We aimed to assess first-degree relatives (FDRs) of Behçet’s disease (BD) patients for the presence of clinical symptoms and signs of BD and evaluate common femoral vein (CFV) wall thickness measurement for the diagnosis.

Methods
Patients with BD (n = 129) and FDRs (n = 230) of these patients were included. FDRs were questioned in terms of BD symptoms by phone. Pathergy test and CFV wall thickness measurement were performed among 111 FDRs who accepted the clinical assessment. Clinical assessment groups were classified according to the criteria sets for BD. FDRs who did not meet the criteria sets and had at least one clinical finding in addition to oral aphthae (OA) were categorized as the ‘suspected BD’.

Results
: We observed increased frequency of isolated BD manifestations in FDRs. Ten FDRs were diagnosed with BD during clinical evaluation. A significantly increased CFV wall thickness was observed in FDRs of BD patients fulfilling diagnostic BD criteria (P &lt; .001 for both sides) and also in those with suspected BD group (P &lt; .05 for both sides). The presence of OA, genital ulcer, folliculitis, or erythema nodosum was associated with increased CFV wall thickness (P &lt; .05).

Conclusion
Our results suggest that the CFV wall thickness measurement can be used in the diagnosis of familial BD.
Enhancing prognostication and treatment response evaluation in primary CNS lymphoma with 18F-FDG-PET/CT
Authors: Oh Minyoung , Cho Hyungwoo , Park Ji Eun , Kim Ho Sung , Go Heounjeong , Park Chan-Sik , Lee Sang-wook , Song Sang Woo , Kim Young-Hoon , Cho Young Hyun , Hong Seok Ho , Kim Jeong Hoon , Lee Dong Yun , Ryu Jin-Sook , Yoon Dok Hyun , Kim Jae Seung 
Published: August 2024

Abstract

Background
The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined.

Methods
We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG).

Results
The median age of the 268 patients was 62 years (range: 17–85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% CI: 19.9–29.1), and the median overall survival (OS) was 34.5 months (95% CI: 22.9–46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥ 17.0 cm3 had significantly shorter OS (12.5 vs 74.0 months, P = .011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs 46.0 months, P = .001) and OS (median: 21.0 vs 62.0 months, P = .002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (P = .130) or OS (P = .540).

Conclusion
Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.
21 Unconventional mechanisms of action and resistance to rapalogs in renal cancer
Authors: Butti Ramesh , Yang Juan , Cohn Shannon , Kapur Payal , Brugarolas James 
Published: August 2024

Abstract

Background
Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer type in the United States driven by inactivation of the von Hippel-Lindau (VHL) gene and with frequent hyperactivation of mammalian target of rapamycin complex 1 (mTORC1). Multiple drugs have been developed to target VEGF/VEGFR2 and mTORC1 for advanced RCC treatment. Two specific mTORC1 inhibitors, temsirolimus and everolimus (known as rapalogs), are FDA-approved for the treatment of RCC but their clinical efficacy is hindered by the emergence of resistance.

Methods
To study the development of rapalog resistance in RCC, we utilized patient-derived tumorgrafts (TGs) implanted in immunocompromised mice and treated the mice with rapamycin for prolonged periods to generate resistance. Resistance was studied by transplanting resistant tumors into additional cohorts of mice and establishing primary cultures. The impact of rapamycin on tumor growth and mTORC1 activity in both tumor and stromal cells was assessed using molecular techniques. To dissect the role of the tumor microenvironment (TME), we generated genetically engineered immunocompromised recipient mice with an mTOR inhibitor resistance mutation (S2035T). Coculture experiments were performed to further explore the interplay.

Results
Prolonged rapamycin treatment resulted in the development of resistance in TGs. Notably, this occurred despite persistent inhibition of mTORC1 in tumor cells. Resistance was transient and lost with subsequent transplantation and in cell culture. Surprisingly, resistance was accompanied by mTORC1 reactivation in the TME, specifically in cancer associated fibroblasts. Introducing an mTOR resistance mutation (S2035T) into recipient mice was sufficient to cause resistance. Co-culture experiments with fibroblasts further demonstrated that rapamycin-resistant mutant fibroblasts conferred resistance in tumor cells even in the absence of mTORC1 activity.

Conclusions
This study uncovers a critical role of the TME, in mediating the response and resistance to rapalogs in RCC. Our data show that inhibition of mTORC1 in non-tumor cells is essential for the anti-tumor activity of rapalogs. These findings shed light on why mTOR mutations are rarely observed in resistant RCC patients and highlight the significance of the TME in modulating drug response and resistance. Moreover, our study emphasizes the potential of targeting TME cells as a therapeutic strategy in RCC and possibly other cancers.
DOD CDMRP Funding: yes
58 Tumor immune microenvironment determinants of response to Lenvatinib and aPD-1 blockade in clear cell renal cell carcinoma
Authors: Vuong Lynda 
Published: August 2024

Abstract

Background
Combinations of immune checkpoint blockade (ICB) and anti-angiogenesis tyrosine kinase inhibitors (TKI) are the mainstay of metastatic ccRCC front-line treatment, but heterogenous responses and lack of biomarkers strongly emphasizes the need to understand RCC-specific mechanisms of effective treatment-related anti-tumor immunity. Although prior work consistently highlights tumor associated macrophages (TAMs) in RCC prognosis and treatment response, TAM targeting has yet to experimentally assessed as a viable treatment sensitizer.

Methods
We therefore assessed the impact of TAM depletion using a clinical-grade colony stimulating factor receptor-1 inhibitor (CSF1Ri) on ICB or TKI sensitivity in a spontaneous mouse model of ccRCC with inducible kidney-specific Vhl, p53 and Rb1 deletions (KVpR). Mice were randomized to receive either no treatment, single agent Lenvatinib (TKI), aPD-1, or combinations with CSF1Ri. We longitudinally monitored a total of 307 tumors from 96 mice using magnetic resonance imaging (MRI) and collected responding and non-responding tumors for single cell RNA sequencing (scRNAseq) to elucidate the underlying mechanisms of response.

Results
Surprisingly we found that TAM depletion abolished aPD-1 response, with no effect on Lenvatinib response. ScRNAseq analyses suggest that CSF1R selectively depletes antigen presenting TAMs, leading to a striking loss of T cell infiltration. This suggests that TAMs, rather than dendritic cells as shown in other cancer types, may play a dominant role in eliciting T cells during aPD-1 therapy in RCC. On the other hand, Lenvatinib, which elicited a stronger T cell response than aPD-1, was associated with significant increases in cDC1 and plasma cells in responders, together suggesting that these two treatment modalities may operate through distinct antigen-presenting cells. Also unexpectedly, we found that both Lenvatinib and CSF1Ri induced severe intratumor hypoxia, which is typically associated with poor outcomes in most cancers. We identify a hypoxic niche-specific TAM subset that when abundant at baseline is predictive for poor response to ICB/TKI combos across multiple RCC trials, but post-treatment seems to capture hypoxia-mediated tumor cell death in responders in mouse and humans. We therefore wondered whether high levels of existing tumor hypoxia would exacerbate TKI-induced hypoxia leading to worst outcomes and found that in two novel RCC syngeneic models with high-baseline hypoxia, TKI indeed augments metastatic disease.

Conclusions
Our results offer mechanistic insight into the failure of CSF1R-based TAM depletion approaches in clinical trials and presents cautionary evidence against the use of hypoxia-inducing agents in tumors with high-baseline hypoxia. We show that TKI and ICB-induce distinct TME and hypoxia-related changes which require further study. More generally our study strongly emphasizes the importance of developing mechanism-guided clinical biomarkers.
DOD CDMRP Funding: yes
Racial-Ethnic Poverty Gaps in Later Life: A Role for Late Career Employment Quality?
Authors: Phillips Lora A , Rhodes Alec P 
Published: August 2024

Abstract
Racial-ethnic disparities in poverty are an important form of inequality in older age. Recent scholarship on racial-ethnic poverty gaps demonstrates that, beyond individual characteristics and behaviors, racialized structural factors like employment contribute to such gaps. Yet surprisingly little is known about the role of employment quality, despite observed racial-ethnic disparities in employment quality and the role of employment history in shaping later life well-being. Using data from the 2002–2018 waves of the Health and Retirement Study (HRS) and three poverty measures, we decompose the proportions of the Black-white and Hispanic-white poverty gaps among households led by 65-year-olds that are attributable to disparities in late career employment quality. We find that racial-ethnic disparities in late career employment quality account for 17–28 percent of the observed Black-white and 18–32 percent of the observed Hispanic-white poverty gaps, thus explaining a greater proportion of such gaps than many common individual or behavioral explanations. Disaggregating employment quality into its component measures, we find racial-ethnic disparities in access to employer-provided health insurance and hourly wages account for the largest proportion of racial-ethnic poverty gaps. Our findings suggest that employment quality captures important racialized dimensions of labor market context that help account for racial-ethnic inequalities in later life poverty in the United States.
Assessment of B-type natriuretic peptide as an early predictor of mortality in acutely poisoned patients with cardiotoxicities
Authors: Elgendy Shaimaa Ali , Shoeib Osama , Elgharbawy Doaa , Abo El-Noor Mona M , Kabbash Abdelmoty 
Published: August 2024

Abstract

Background
Cardiotoxicity is a major toxic effect induced by several types of drugs. An electrocardiogram is done routinely in cardiovascular drug exposures. Cardiac troponin I (cTnI) is the usual biomarker for diagnosing myocardial injury. B-type natriuretic peptide (BNP) is a well-established predictor of disease state in suspected heart failure.

Aim
The study aimed to assess BNP’s role as an early predictor of mortality compared with cTnI and ECG changes in acutely poisoned patients with cardiotoxicities.

Methodology
This study enrolled 70 patients with acute cardiotoxicity by drugs and toxins known to cause cardiac injury admitted to Tanta University Poison Control Center (TUPCC). Collected data included socio-demographic data, toxicological history, vital signs, ECG changes, Poison Severity Score (PSS), BNP, and cTnI serum levels.

Result
Patients were classified as survivors and non-survivors. Significantly more delay time was recorded in non-survivors. Moreover, vital signs were significantly abnormal in non-survivors. There was no statistical significance regarding the initial ECG abnormalities between survivors and non-survivors. BNP and cTnI levels were significantly higher among non-survivors. For mortality prediction, BNP had good predictive power (AUC = 0.841) with 100% sensitivity and 79.7% specificity while cTnI had an acceptable predictive power (AUC = 0.786), with 83.3% sensitivity and 78.1% specificity with insignificant difference between both biomarkers.

Conclusion
BNP and cTnI levels can predict mortality in acute cardiotoxicity compared to ECG which has no statistically significant prediction. BNP has a higher discriminatory power than cTnI for the prediction of mortality.
CPD Success With Technagogy in Health Professions: Determinants and Merits
Authors: Ong Irvin , Dino Michael Joseph , Enriquez Caroline Marian , Gotinga Trisha Joy , Esluzar Corazon , Cajayon Sharon , Buencamino Arnel , Pimentel-Tormon Fraulein , Rodriguez Angelita , Tablizo Alicia 
Published: August 2024

Introduction:
Continuing professional development (CPD) has become a common strategy to address the gaps in knowledge and competencies during the pandemic. Given the drastic changes in the learning environment, this study explored “technagogy” or teaching with technology in CPD in the health professions.

Methods:
A mixed-methods study was used to ascertain the determinants and merits of CPD success from the participants' perspectives (n = 237). The quantitative data underwent structural equation modeling using partial least squares. We also thematically analyzed the qualitative responses and synthesized concurrent findings.

Results:
The structural model accounted for a 64% variance in the CPD success. Its significant direct predictors (P < .05) were instructional, curriculum, and nurturant effects. From the participants' experiences, we generated four themes as the merits of CPD: learning, teaching, knowledge, and technology scholarships. Finally, we constructed a synthesized model, the CPD Determinants and Intrinsic Assets in Learning, which can offer modest guidance in navigating CPD with technagogy.

Discussion:
The study findings emphasize the convergence and divergence points as considerations in teaching and learning with technology. It also offers valuable insights into relevant implications of technagogy in CPD, including its theory, practice, policy, and research.
Outcomes of manual arcuate keratotomy with compression sutures for high regular postkeratoplasty astigmatism
Authors: Berger Tim , Abu Dail Yaser , Seitz Berthold , Khattabi Zaynab , Flockerzi Elias , Hamon Loic , Langenbucher Achim , Daas Loay 
Published: August 2024

Purpose:
To report functional and refractive outcomes of manual arcuate keratotomy (AK) with compression sutures for high regular postkeratoplasty astigmatism.

Setting:
Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.

Design:
Retrospective analysis.

Methods:
This study included 90 eyes with high regular postkeratoplasty astigmatism (>4 diopters [D]) who received AK with compression sutures between 2010 and 2022. Functional and refractive outcomes were assessed by evaluating topographic indices and by performing vector astigmatism and Fourier analysis.

Results:
At last follow-up (mean 13.7 ± 16.6 months), corrected distance visual acuity improved from 0.59 ± 0.28 to 0.34 ± 0.25 logMAR. Cylinder magnitude decreased from 9.91 ± 2.88 to 5.42 ± 3.35 D. Surface asymmetry index, irregular astigmatism index, and corneal eccentricity index were equal to preoperative values, whereas surface regularity index approached normal values at last follow-up. Fourier analysis indicated a decrease in the regular astigmatic component, whereas nonregular components (asymmetry and higher-order irregularity) remained stable. In vector astigmatism analysis, target-induced astigmatism magnitude was 9.92 ± 2.86 D and surgically induced astigmatism magnitude was 10.16 ± 4.86 D (correction index of 0.91 ± 0.48) with a difference vector of 5.42 ± 3.35 D at last follow-up. Correction of astigmatism magnitude was adequate in 40% of the eyes, undercorrected in 30%, and overcorrected in 30%. Angle of error was <|22.5 degrees| in 88% resulting in a low risk of off-axis treatment.

Conclusions:
AK with compression sutures is a simple, relatively effective, and safe surgical procedure for astigmatism reduction after keratoplasty. In case of regular astigmatism, the procedure does not increase corneal irregularities. The remaining refractive error might be further corrected by spectacles, contact lenses, or toric intraocular lens implantation (in-the-bag/add-on), thus reducing the need for repeat keratoplasty.
Long-term intrathecal infusion of low-dose morphine effectively relieves symptoms of severe restless legs syndrome/Willis–Ekbom disease without inducing opioid tolerance
Authors: Janerås Lars , Breivik Harald , Lundeland Bård , Ringstad Geir Andre , Stubhaug Audun 
Published: August 2024

Abstract
Restless legs syndrome/Willis–Ekbom disease (RLS/WED) causes a strong urge to move legs while resting. Restless legs syndrome/WED is an often-inherited disease occurring in 3% to 10% of adult populations, increasing with age. Severity varies from mild disturbance of sleep to painful restless legs and arms, loss of sleep, fatigue, and risk of suicide. Dopaminergic drugs relieve symptoms, but cause augmentation, ie, initially helpful but later increase the burden of symptoms. Oral gabapentinoids and opioids are often added, but opioid tolerance and adverse effects are common. With the high prevalence and incomplete help from oral drugs, significant unmet needs exist for effective therapy for severe RLS/WED. Ongoing spinal intrathecal infusion of low-dose morphine is effective, but not generally recognized, as only 12 cases have been published since 2002. We report 7 patients suffering from severe RLS/WED, who had no relief from oral dopaminergic, gabapentinoid, or opioid drugs; they all had excellent relief during ongoing spinal intrathecal infusion of morphine at only 1 to 5 μg/h, ongoing for 1 to 21 years without need of higher doses of morphine.. We suggest that morphine may be transported with the cerebrospinal fluid reaching and readjusting malfunctioning dopamine neuronal systems in the brain and spinal cord. The effects last only as long as the infusion continues. A patient with RLS/WED and persistent genital arousal disorder (PGAD) was relieved of both RLS/WED and PGAD symptoms. These case reports suggest that intrathecal infusion of low-dose morphine is an effective treatment of severe RLS.