bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tectonic fractures induced by strike-slip faulting in intracratonic ultradeep carbonate rocks: Insights from the finite element method and self-adaptive constraints computational model for boundary conditions
Authors: Li Yuntao , Ding Wenlong , Han Jun , Chen Xuyun , Huang Cheng , Li Jingtian , Ding Shihao 
Published: April 2024

Abstract
Numerical simulations of the paleostress field during a period of tectonic fracture formation and rock failure criteria are used to quantitatively predict the development and occurrence of tectonic fractures induced by the formation of the SB18 fault zone in the Middle Ordovician Yijianfang Formation of the Shunnan area, Tarim Basin, China. The results of acoustic emission experiments, mechanical property measurements, and tectonic fracture occurrence observations obtained from core descriptions and fullbore formation microimager logs are combined with the Andersonian model of faulting and the finite element method, which is widely used for the numerical simulation of stress fields, to investigate the paleotectonic and in situ stress fields via numerical simulation. The quantitative prediction of the opening pressure and opening sequence of tectonic fractures is based on the occurrence of tectonic fracture, numerical simulation of in situ stresses, and coordinate system conversion. The results show that the width of the fracture zone induced by strike-slip faulting is ~310 m. The degree of fracture development is significantly increased when the Young’s modulus, paleostress difference, and paleostress difference coefficient of the rock are elevated. The current horizontal principal stress is positively correlated with the distance from the fault, and the elevated areal density of the secondary faults causes a clockwise deflection of the horizontal stress direction. SSE-striking shear fractures with orientations ranging from 140° to 150° and two sets of tensional fractures with orientations ranging from −40° to −35° and 55° to 60° are preferentially opened in the water injection development stage of the reservoir. As the horizontal stress difference, horizontal stress difference coefficient, and angle between the maximum horizontal principal stress and a fracture decrease, the fracture opening pressure decreases. At the structural highs (burial depths &lt;6225 m) and lows (burial depths &gt;6225 m), the fracture burial depth is positively and negatively correlated with the opening pressure, respectively. Quantitative prediction of tectonic fracture developmental characteristics, opening pressure, and the opening sequence and investigation of the main factors that control their development can help to identify and support opportunities for hydrocarbon exploration and development of fractured carbonate reservoirs.
Impact of informal caregiving on depressive symptoms among a national cohort of men
Authors: King Tania L , Vitaliano Peter P , Maheen Humaira , Taouk Yamna 
Published: April 2024

BackgroundThere is evidence that unpaid caregiving can have negative effects on the mental health of female caregivers; however, evidence of impacts on male caregivers is limited. This study addressed this gap by examining associations between becoming a caregiver and depressive symptoms among men.MethodsWe used data from waves 1–2 (2013, 2016) of the Longitudinal Study of Australian Male Health (Ten to Men). Effects of incident caregiving on depressive symptoms were estimated using augmented inverse probability treatment weighting, with adjustment for potential confounders. Incident caregiving was assessed as a binary variable (became a caregiver vs not), and depressive symptoms were measured using the Patient Health Questionnaire (moderate to severe depressive symptoms; yes, no). Main analysis was prospective, drawing on wave 1 (caregiving) and wave 2 (depressive symptoms), and sensitivity analyses modelled cross-sectional associations.ResultsIn the main analysis, incident caregiving in wave 1 was associated with depressive symptoms in the subsequent wave, with an average treatment effect of 0.11 (95% CI 0.06, 0.17) and equating to a risk ratio of 2.03 (95% CI 1.55, 2.51). Associations were robust to several sensitivity analyses, with cross-sectional associations supporting the main prospective analyses.ConclusionThese results provide evidence of the association between caregiving and depressive symptoms among male caregivers. This has important implications for policy and support programmes. As we seek to shift caregiving responsibilities toward a more gender-equal distribution of care, policy must recognise that, like female caregivers, male caregivers also experience mental health impacts related to their caregiving role.
Treatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A)
Authors: Atkins Michael B , Jegede Opeyemi A , Haas Naomi B , Mcdermott David F , Bilen Mehmet A , Stein Mark , Sosman Jeffrey , Alter Robert , Plimack Elizabeth R , Ornstein Moshe C , Hurwitz Michael , Peace David J , Einstein David , Catalano Paul J , Hammers Hans , Regan Meredith M 
Published: April 2024

BackgroundAs part of a partitioned survival analysis, treatment-free survival (TFS) can characterize the overall survival time patients spend between the cessation of immunotherapy and the start of subsequent therapy; both with and without toxicity. Significant TFS was reported for the nivolumab/ipilimumab arms of the CheckMate 067 and 214 trials for patients with advanced melanoma or renal cell carcinoma (aRCC), respectively, where immunotherapy was often halted for toxicity rather than a predefined treatment endpoint. We therefore sought to assess TFS in the HCRN GU16-260 trial, which was designed to reduce toxicity and cap immunotherapy duration.MethodsData were analyzed from 128 patients with clear-cell aRCC treated with first-line nivolumab monotherapy for up to 2 years. Salvage nivolumab/ipilimumab for up to 1 year was provided to eligible patients with disease progression at any point or stable disease at 48 weeks (29% of patients). TFS was defined as the area between Kaplan-Meier curves for a time from registration to protocol therapy cessation and for a time from registration to subsequent systemic therapy initiation or death, estimated from 36-month mean times. The time on or off protocol treatment with grade 3+treatment-related adverse events (TRAEs) was also captured.ResultsAt 36 months from enrollment, 68.3% of patients were alive: 96.8% of International Metastatic RCC Database Consortium (IMDC) favorable-risk patients and 56.6% of those with intermediate/poor-risk, respectively. The 36-month mean time on protocol therapy was 11.5 months including 0.6 months with grade 3+TRAEs (16.0 months for favorable-risk patients and 9.6 months for intermediated/poor-risk patients). The 36-month mean TFS for the whole population was 9.4 months (12.9 months including 1.5 months with grade 3+TRAEs for favorable-risk and 8.0 months including 1.0 months with grade 3+TRAEs for intermediate/poor-risk). At 36 months, 65.6% of favorable-risk patients and 27.1% of intermediate/poor-risk patients were alive and subsequent systemic treatment-free.ConclusionsNivolumab monotherapy with salvage nivolumab/ipilimumab in non-responders is an active treatment approach in treatment-naïve patients with aRCC and, similar to nivolumab/ipilimumab in CheckMate 214, results in substantial TFS and toxicity-free TFS. TFS was greatest in patients with favorable-risk disease, supporting the use of an immunotherapy-only regimen in this population.
Oral PD-L1 inhibitor GS-4224 selectively engages PD-L1 high cells and elicits pharmacodynamic responses in patients with advanced solid tumors
Authors: Odegard Jared M , Othman Ahmed A , Lin Kai-Wen , Wang Adele Y , Nazareno Jonathan , Yoon Oh Kyu , Ling John , Lad Latesh , Dunbar P Rod , Thai Dung , Ang Edmond , Waldron Nicholas , Deva Sanjeev 
Published: April 2024

BackgroundCheckpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies in a range of immunogenic cancer types. Blocking this pathway with an oral therapy could benefit patients through greater convenience, particularly in combination regimens, and allow flexible management of immune-mediated toxicities.MethodsPD-L1 binding activity was assessed in engineered dimerization and primary cell target occupancy assays. Preclinical antitumor activity was evaluated in ex vivo and in vivo human PD-L1-expressing tumor models. Human safety, tolerability, pharmacokinetics, and biomarker activity were evaluated in an open-label, multicenter, sequential dose-escalation study in patients with advanced solid tumors. Biomarkers evaluated included target occupancy, flow cytometric immunophenotyping, plasma cytokine measurements, and T-cell receptor sequencing.ResultsGS-4224 binding caused dimerization of PD-L1, blocking its interaction with PD-1 and leading to reversal of T-cell inhibition and increased tumor killing in vitro and in vivo. The potency of GS-4224 was dependent on the density of cell surface PD-L1, with binding being most potent on PD-L1–high cells. In a phase 1 dose-escalation study in patients with advanced solid tumors, treatment was well tolerated at doses of 400–1,500 mg once daily. Administration of GS-4224 was associated with a dose-dependent increase in plasma GS-4224 exposure and reduction in free PD-L1 on peripheral blood T cells, an increase in Ki67 among the PD-1-positive T-cell subsets, and elevated plasma cytokines and chemokines.ConclusionsGS-4224 is a novel, orally bioavailable small molecule inhibitor of PD-L1. GS-4224 showed evidence of expected on-target biomarker activity, including engagement of PD-L1 and induction of immune-related pharmacodynamic responses consistent with PD-L1 blockade.Trial registration numberNCT04049617.
Longitudinal analysis of PD-L1 expression in patients with relapsed NSCLC
Authors: John Nikolaus , Schlintl Verena , Sassmann Teresa , Lindenmann Jörg , Fediuk Melanie , Wurm Robert , Douschan Philipp , Zacharias Martin , Kalson Lipika , Posch Florian , Absenger Gudrun , Brcic Luka , Jost Philipp J , Terbuch Angelika 
Published: April 2024

BackgroundThe use and approval of immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) depends on PD-L1 expression in the tumor tissue. Nevertheless, PD-L1 often fails to predict response to treatment. One possible explanation could be a change in PD-L1 expression during the course of the disease and the neglect of reassessment. The purpose of this study was a longitudinal analysis of PD-L1 expression in patients with relapsed NSCLC.MethodsWe retrospectively analyzed PD-L1 expression in patients with early-stage NSCLC and subsequent relapse in preoperative samples, matched surgical specimens and biopsy samples of disease recurrence. Ventana PD-L1 (SP263) immunohistochemistry assay was used for all samples. PD-L1 expression was scored based on clinically relevant groups (0%, 1%–49%, and ≥50%). The primary endpoint was the change in PD-L1 score group between preoperative samples, matched surgical specimens and relapsed tumor tissue.Results395 consecutive patients with stages I–III NSCLC and 136 (34%) patients with a subsequent relapse were identified. For 87 patients at least two specimens for comparison of PD-L1 expression between early stage and relapsed disease were available. In 72 cases, a longitudinal analysis between preoperative biopsy, the surgically resected specimen and biopsy of disease recurrence was feasible. When comparing preoperative and matched surgical specimens, a treatment-relevant conversion of PD-L1 expression group was found in 25 patients (34.7%). Neoadjuvant treatment showed no significant effect on PD-L1 alteration (p=0.39). In 32 (36.8%) out of 87 cases, a change in PD-L1 group was observed when biopsies of disease relapse were compared with early-stage disease. Adjuvant treatment was not significantly associated with a change in PD-L1 expression (p=0.53). 39 patients (54.2%) showed at least 1 change into a different PD-L1 score group during the course of disease. 14 patients (19.4%) changed the PD-L1 score group twice, 5 (6.9%) of them being found in all different score groups.ConclusionPD-L1 expression shows dynamic changes during the course of disease. There is an urgent need for consensus guidelines to define a PD-L1 testing strategy including time points of reassessment, the number of biopsies to be obtained and judgment of surgical specimens.
Day-to-day variation in trace and macro-mineral concentrations in corn and mixed grass–legume silages of Canadian commercial dairy herds
Authors: Duplessis M. , Dubois K. , Royer I. 
Published: April 2024

The aims were to assess the day-to-day variation in trace minerals (TM), macro-minerals, dry matter, and physical effectiveness factor in grass–legume and corn silages and to evaluate the variance partition. Grass–legume and corn silage samples were collected in nine Canadian dairy herds during two episodes of five consecutive days at 4 weeks apart by the same individual. All variables were analyzed in duplicate. The proportion of variation due to the farm was more variable within TM than macro-minerals. Using TM software reference values of silages for formulating rations can lead to important errors. Except for physical effectiveness factor, the within-farm variations between sampling episodes were more marked for mixed grass–legume than corn silage. For most of the minerals and nutrients analyzed, the sampling + day-to-day variations were the main source of variability, accounting for over 50% of the within-farm variance for both silage types. The remaining within-farm variance was explained by subsampling and laboratory analyses. The high within-herd variation suggests that a silage sampling over more than 1 day can be useful to get a representative sample for TM analysis. Accurate nutrients and TM values when formulating cow diets is essential to cow health and productivity.
Strong gravitational lensing, quasi-periodic oscillations and constraints from EHT observations for quantum-improved charged black hole
Authors: Molla Niyaz Uddin , Chaudhary Himanshu , Mustafa G. , Debnath Ujjal , Maurya S. K. 
Published: April 2024

AbstractWe investigate strong gravitational lensing by quantum-improved charged black holes characterized by an additional parameter denoted as $$\omega $$
ω
, in addition to the mass M and charge Q. Our findings reveal that when both the parameters Q/2M and $$\omega /4M^2$$

ω
/
4

M
2

increase simultaneously, various astrophysical consequences, such as the deflection angle $$\alpha _D(u)$$

α
D

(
u
)

and angular image separation increase. Concurrently, the angular position $$\theta _{\infty }$$

θ
∞

, relative magnification $$r_{mag}$$

r

mag

, and the time delay $$\Delta T_{2,1}$$

Δ

T

2
,
1

between the first and second relativistic images also decrease with the growing values of the parameters Q/2M and $$\omega /4M^2$$

ω
/
4

M
2

. It is also observed that the Einstein ring $$\theta _1^E$$

θ
1
E

for the quantum-improved charged black hole is more significant than those for Schwarzschild, quantum-improved Schwarzschild, and Reisner–Nordström black holes. As with supermassive black holes such as $$M87^*$$

M

87
∗

and $$SgrA^*$$

S
g
r

A
∗

, it is observed that to be a viable astrophysical black hole, the EHT results constrain the parameter space ($$\omega /4M^2$$

ω
/
4

M
2

, Q/2M). Remarkably, the EHT results for $$SgrA^*$$

S
g
r

A
∗

impose more stringent limits on the parameter space of quantum-improved charged black holes compared to those established by the EHT results for$$M87^*$$

M

87
∗

. We investigate the radial profiles of orbital and radial harmonic oscillation frequencies as a function of the dimensionless coupling constants and black hole mass. The main characteristics of test particle quasi-periodic oscillations close to stable circular orbits in the black hole equatorial plane are also examined. We study the positioning of resonant radii in the background of quantum-improved charged black holes for high-frequency quasi-periodic oscillations models: warped disc (WD) models, relativistic precession (RP) and its types, and epicyclic resonance (ER) and its variants.
Visual Estimates of Coronary Slow Flow Are Not Associated With Invasive Wire-Based Diagnoses of Coronary Microvascular Dysfunction
Authors: Harkin Kenneth L. , Loftspring Ethan , Beaty William , Joa Amanda , Serrano-Gomez Claudia , Farid Ayman , Hausvater Anaïs , Reynolds Harmony R. , Smilowitz Nathaniel R. 
Published: April 2024

BACKGROUND:
Coronary slow flow (CSF) by invasive coronary angiography is frequently understood to be an indicator of coronary microvascular dysfunction (CMD) in patients with ischemia with nonobstructive coronary arteries. However, the relationship between visual estimates of CSF and quantitative wire-based invasive diagnosis of CMD is uncertain.

METHODS:
We prospectively enrolled adults aged ≥18 years with stable ischemic heart disease who were referred for invasive coronary angiography. Individuals with ≥50% epicardial coronary artery stenosis were excluded. Invasive coronary angiography was reviewed for CSF, defined as ≥3 cardiac cycles to opacify distal vessels with contrast. Coronary function testing was performed in the left anterior descending coronary artery using bolus coronary thermodilution techniques to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Invasively determined CMD was defined as abnormal CFR (<2.5), abnormal IMR (≥25), or both.

RESULTS:

Among 104 participants, the median age was 61.5 years and 79% were female. The median CFR was 3.6 (interquartile range, 2.5–4.7) and the median IMR was 21 (interquartile range, 13.3–28.0). Overall, 24.0% of participants had abnormal CFR, 34.6% had abnormal IMR, and 48.1% had a final diagnosis of invasively determined CMD. CSF was present in 23 participants (22.1%). The proportions of patients with CMD (56.5% versus 45.7%;
P
=0.36), abnormal CFR (17.4% versus 25.9%;
P
=0.40), and abnormal IMR (43.5% versus 32.1%;
P
=0.31) were not different in patients with versus without CSF.

CONCLUSIONS:
Among patients with ischemia with nonobstructive coronary artery, CSF was not associated with abnormal CFR, IMR, or either abnormal CFR or IMR. CSF is not a reliable angiographic surrogate of abnormal CFR or IMR as determined by invasive, wire-based physiology testing.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03537586.
Randomized Evaluation of a Remote Management Program to Improve Guideline-Directed Medical Therapy: The DRIVE Trial
Authors: Blood Alexander J. , Chang Lee-Shing , Hassan Shahzad , Chasse Jacqueline , Stern Gretchen , Gabovitch Daniel , Zelle David , Colling Caitlin , Aronson Samuel J. , Figueroa Christian , Collins Emma , Ruggiero Ryan , Zacherle Emily , Noone Joshua , Robar Carey , Plutzky Jorge , Gaziano Thomas A. , Cannon Christopher P. , Wexler Deborah J. , Scirica Benjamin M. 
Published: April 2024

BACKGROUND:
Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations.

METHODS:
A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP1-RA by 6 months.

RESULTS:

Between March 2021 and December 2022, 200 patients were randomized. The mean age was 66.5 years; 36.5% were female, and 22.0% were non-White. Overall, 30.0% had cardiovascular disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate was 77.9 mL/(min‧1.73 m
2
), and mean urine/albumin creatinine ratio was 88.6 mg/g. After 2 months, 69 of 200 (34.5%) patients received a new prescription for either SGLT2i or GLP1-RA: 53.4% of patients in the Simultaneous arm and 8.3% of patients in the Education-First arm (
P
<0.001). After 6 months, 128 of 200 (64.0%) received a new prescription: 69.8% of patients in the Simultaneous arm and 56.0% of patients in Education-First (
P
<0.001). Patient self-report of taking SGLT2i or GLP1-RA within 6 months of trial entry was similarly greater in the Simultaneous versus Education-First arm (69 of 116 [59.5%] versus 37 of 84 [44.0%];
P
<0.001) Median time to first prescription was 24 (interquartile range [IQR], 13–50) versus 85 days (IQR, 65–106), respectively (
P
<0.001).

CONCLUSIONS:
In this randomized trial, a remote, team-based program identifies patients with type 2 diabetes and high cardiovascular or kidney risk, provides virtual education, prescribes SGLT2i or GLP1-RA, and improves guideline-directed medical therapy. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT06046560.