bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of passive leg raising on the cross-sectional area of the right internal jugular vein in patients with obesity: a randomised controlled trial protocol
Authors: Pei Dongliang , Wang Shuyan , Sun Chenmin 
Published: May 2024

BackgroundVenous access in patients with obesity presents significant challenges. The success of central venous catheterisation largely depends on the cross-sectional area (CSA) of the internal jugular vein (IJV). While techniques like the Trendelenburg position have been traditionally used to increase IJV CSA, recent studies suggest its ineffectiveness in patients with obesity. Conversely, the potential of the effect of passive leg raising (PLR) has not been thoroughly investigated in this group of patients.MethodsThis protocol outlines a planned randomised controlled trial to evaluate the effect of PLR on the CSA of the IJV in patients with obesity slated for central venous catheterisation. The protocol involves dividing 40 participants into two groups: one undergoing PLR and another serving as a control group without positional change. The protocol specifies measuring the CSA of the IJV via ultrasound as the primary outcome. Secondary outcomes will include the success rates of right IJV cannulation. The proposed statistical approach includes the use of t-tests to compare the changes in CSA between the two groups, with a significance threshold set at p<0.05.Ethics approvalThis study has been approved by the Institutional Review Board of Shanghai Tongren Hospital. All the participants will provide informed consent prior to enrolment in the study. Regarding the dissemination of research findings, we plan to share the results through academic conferences and peer-reviewed publications. Additionally, we will communicate our findings to the public and professional communities, including patient advocacy groups.Trial registration numberChiCTR: ChiCTR2400080513.
Development of indicators to measure health system capacity for quality abortion care in 10 countries: a rapid assessment of a measurement framework and indicators
Authors: Johnston Heidi Bart , Rehnstrom Loi Ulrika , Ali Mohamed , Footman Katy , Alinsato Ghislaine Glitho , Aly Eman , Chilanga Asmani , Bansal Shikha , Codjia Laurence , Dkhimi Fahdi , Dlamini-Nqeketo Sithembile , Elamin Hayfa , Gbenou Dina , Gholbzouri Karima , Hedman Lisa , Hemachandra Nilmini , Hien Yelmali , Hyder Md Khurshid Alam , John Theopista , Kansal Amrita , Karna Priya , Läser Laurence , Lavelanet Antonella , Mihretu Belete , Onyiah Pamela Amaka , Ouedraogo Leopold , Qais Sikander , Thom Ellen , Upadhyay Meera , Uzma Qudsia , Zan Souleymane , Ganatra Bela 
Published: May 2024

IntroductionA significant gap exists in the availability of indicators and tools to monitor health system capacity for quality abortion care at input and process levels. In this paper, we describe the process and results of developing and assessing indicators to monitor health system capacity strengthening for quality abortion care.MethodsAs part of a 4-year (2019–2022) multicountry project focused on preventing unsafe abortion using a health system strengthening approach in 10 countries, we developed a monitoring framework with indicators and metadata. Through an internal consultative process, we identified a structured list of operational health system capacity indicators for abortion. After implementing the indicators for baseline and annual project monitoring, project staff from 10 teams assessed each indicator using 4 criteria: validity, feasibility, usefulness and importance.ResultsWe identified 30 indicators aligning with 5 of the 6 WHO health system building blocks (excluding service delivery): 6 indicators in leadership and governance, 5 in health workforce, 6 in health information, 8 in access to medicines and health products and 5 in health financing. In our assessment of indicators, average scores against the predetermined criteria were lowest for feasibility (7.7 out of 10) compared with importance (8.5), usefulness (8.9) and validity (9.3). Assessors highlighted the need for fewer and less complex indicators, simplified language, clearer benchmarks, for indicators to be abortion-specific, less subjective and for future frameworks to also include service delivery and research and innovation.ConclusionWe used 30 indicators to monitor health system capacity for quality abortion care in 10 countries and gathered critical feedback that can be used to further strengthen the set of indicators in future work. Establishing core input and process indicators will be critical to inform and support evidence-based policy and programme improvements for quality abortion care.
Bulk-boundary thermodynamics of charged black holes in higher-derivative theory
Authors: Punia Gurmeet Singh 
Published: May 2024

AbstractThe connection between bulk and boundary thermodynamics in Einstein–Maxwell theory is well established using AdS/CFT correspondence. In the context of general higher-derivative gravity coupled to a U(1) gauge field, we examine the resemblance of the first law of thermodynamics between bulk and boundary, followed by an extended phase space description on both sides. Higher-derivative terms related to different powers of the string theory parameter $$\alpha '$$

α
′

emerged from a consistent truncation in the bulk supergravity action. We demonstrate that one must include the fluctuation of $$\alpha '$$

α
′

in the bulk thermodynamics as a bookkeeping tool to match the bulk first law and Smarr relation with the boundary side. Consequently, the Euler relation and the boundary first law are altered by adding two central charges $$({\texttt{a}}, {\texttt{c}}).$$

(
a
,
c
)
.

To support our general conclusion, we consider the black hole in Gauss–Bonnet gravity and the general four-derivative theory. Finally, we examine the bulk and boundary aspects of the extended phase space description for higher-derivative-corrected black holes.
Angular correlation function from sample covariance with BOSS and eBOSS LRG
Authors: Ferreira Paula S. , Reis Ribamar R. R. 
Published: May 2024

AbstractThe Baryon Acoustic Oscillations (BAO) are one of the most used probes to understand the accelerated expansion of the Universe. Traditional methods rely on fiducial model information within their statistical analysis, which may be a problem when constraining different families of models. This work aims to provide a method that constrains $$\theta _{BAO}$$

θ

BAO

through a model-independent approach using the covariance matrix from the galaxy sample from thin redshift bins, later validated with a mock sample covariance matrix. We used widths of $$\delta z = 0.002$$

δ
z
=
0.002

separation for all samples as the basis for a sample covariance matrix weighted by the statistical importance of the redshift bin. Each sample belongs to the Sloan Digital Sky Survey: BOSS1, BOSS2, and eBOSS, with effective redshift $$z_{eff}$$

z

eff

: 0.35, 0.51, 0.71, and different numbers of bins with 50, 100, and 200. To get $$\theta _{BAO}$$

θ

BAO

, we correct the angular separation from the polynomial fit ($$\theta _{fit}$$

θ

fit

) by comparing each bin correlation function with the correlation function of the whole set, a parameter named $$\tilde{\alpha }$$

α
~

. We also tested such correction by choosing the bin at $$z_{eff}$$

z

eff

and found that for eBOSS $$\theta _{BAO}$$

θ

BAO

is in $$1 \sigma $$

1
σ

agreement with the Planck 18 model. Finally, we found that the sample covariances are noisy compared to the mocks for lower z samples, something expected due to nonlinear effects. Such noise impact can be seen in the parameter constraints but does not affect the eBOSS covariance sample. It is shown that mocks’ results do tend to its chosen fiducial cosmology $$\theta _{BAO}$$

θ

BAO

. BOSS1 and BOSS2 showed agreement with Planck 18 and an agreement with Pantheon + S$$H_0$$

H
0

ES when $$\tilde{\alpha }$$

α
~

is based on the bin $$z=z_{eff}$$

z
=

z

eff

.
Health Capacity to Work among Older People in Thailand
Authors: ZHAO JIAYING , LAW CHI KIN , PIGGOTT JOHN , YIENGPRUGSAWAN VASOONTARA SBIRAKOS 
Published: May 2024

Thailand’s aging population has impacted its labor force. This study examines additional health capacity to work (AHCW) with established methods. Data were obtained from the mortality registry as well as national health, aging, labor force, and welfare surveys. Utilizing the Milligan–Wise method, the estimated AHCW for those aged 50–69 was 1.3 years (an 8.7% increase) for males and 1.9 years (17.8%) for females, based on the 2005 employment–mortality relationship. With the Cutler–Meara–Richards-Shubik method, the estimated AHCW for those aged 60–69 in 2015 ranged from 0.9 years (13.6%) to 2.0 years (31.3%) for males and from 1.2 years (23.2%) to 1.5 years (29.6%) for females. We also found that older informal workers in Thailand need to work to maintain their standards of living due to limited retirement benefits. Effective policy measures should be implemented to protect informal workers’ health, prevent pensioners from being impoverished, facilitate a more flexible working environment, and help workers maintain skills and job competencies.
Antibody–Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients with Breast Cancer
Authors: Bardia Aditya , Sun Sheng , Thimmiah Nayana , Coates James T. , Wu Bogang , Abelman Rachel O. , Spring Laura , Moy Beverly , Ryan Phoebe , Melkonyan Mark N. , Partridge Ann , Juric Dejan , Peppercorn Jeffrey , Parsons Heather , Wander Seth A. , Attaya Victoria , Lormil Brenda , Shellock Maria , Nagayama Aiko , Bossuyt Veerle , Isakoff Steven J. , Tolaney Sara M. , Ellisen Leif W. 
Published: May 2024

Abstract

Purpose:
The antibody–drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule.

Patients and Methods:
In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or sequential (N = 23) schedule. Outcome measures included safety, tolerability, preliminary efficacy, and establishment of a recommended phase 2 dose.

Results:
We hypothesized that tumor-selective delivery of TOP1i via SG would reduce nontumor toxicity and create a temporal window, enabling sequential dosing of SG and PARP inhibition. In vitro, sequential SG followed by TZP delayed TOP1 cleavage complex clearance, increased DNA damage, and promoted apoptosis. In the clinical trial, sequential SG/TZP successfully met primary objectives and demonstrated median progression-free survival (PFS) of 7.6 months without dose-limiting toxicities (DLT), while concurrent dosing yielded 2.3 months PFS and multiple DLTs including severe myelosuppression.

Conclusions:
While SG dosed concurrently with TZP is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG followed by TZP proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies.
Pan-Cancer Interrogation of B7-H3 (CD276) as an Actionable Therapeutic Target Across Human Malignancies
Authors: Miller Carly D. , Lozada John R. , Zorko Nicholas A. , Elliott Andrew , Makovec Allison , Radovich Milan , Heath Elisabeth I. , Agarwal Neeraj , Mckay Rana R. , Garje Rohan , Bastos Bruno R. , Hoon Dave S.B. , Orme Jacob J. , Sartor Oliver , VanderWalde Ari , Nabhan Chadi , Sledge George , Shenderov Eugene , Dehm Scott M. , Lou Emil , Miller Jeffrey S. , Hwang Justin H. , Antonarakis Emmanuel S. 
Published: May 2024

Abstract

B7-H3 (CD276) is a transmembrane glycoprotein of the B7 immune checkpoint superfamily that has emerged as a promising therapeutic target. To better understand the applicability of B7-H3–directed therapies, we analyzed 156,791 samples comprising 50 cancer types to interrogate the clinical, genomic, transcriptomic, and immunologic correlates of B7-H3 mRNA expression. DNA (592-gene/whole-exome) and RNA (whole-transcriptome) sequencing was performed from samples submitted to Caris Life Sciences. B7-H3 high versus low expression was based on top and bottom quartiles for each cancer type. Patients’ overall survival was determined from insurance claims data. Pathway analysis was performed using gene set enrichment analyses. Immune cell fractions were inferred using quanTIseq. B7-H3 is expressed across several human malignancies including prostate, pancreatic, ovarian, and lung cancers. High B7-H3 expression is associated with differences in overall survival, possibly indicating a prognostic role of B7-H3 for some cancers. When examining molecular features across all cancer types, we did not identify recurrent associations between B7-H3 expression and genetic alterations in TP53, RB1, and KRAS. However, we find consistent enrichment of epithelial-to-mesenchymal transition, Wnt, TGFβ, and Notch signaling pathways. In addition, tumors with high B7-H3 expression are associated with greater proportions of M1 macrophages, but lower fractions of CD8+ T cells. We have begun to define the genomic, transcriptomic, clinical, and immunologic features associated with B7-H3 expression in 50 cancer types. We report novel clinical and molecular features of B7-H3–high tumors which may inform how current B7-H3 therapeutics should be deployed and prioritized.

Significance:
B7-H3–targeting therapeutics have shown promising results in initial clinical trials. In this pan-cancer analysis of B7-H3 mRNA expression, we found that B7-H3 exhibits robust expression in many common cancer types. These results may inform further development of B7-H3–targeting therapeutics and may guide clinical decisions for patients with limited treatment options.
Use of Deep Learning to Evaluate Tumor Microenvironmental Features for Prediction of Colon Cancer Recurrence
Authors: Sinicrope Frank A. , Nelson Garth D. , Saberzadeh-Ardestani Bahar , Segovia Diana I. , Graham Rondell P. , Wu Christina , Hagen Catherine E. , Shivji Sameer , Savage Paul , Buchanan Dan D. , Jenkins Mark A. , Phipps Amanda I. , Swallow Carol , LeMarchand Loic , Gallinger Steven , Grant Robert C. , Pai Reetesh K. , Sinicrope Stephen N. , Yan Dongyao , Shanmugam Kandavel , Conner James , Cyr David P. , Kirsch Richard , Banerjee Imon , Alberts Steve R. , Shi Qian , Pai Rish K. 
Published: May 2024

Abstract

Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphologic features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphologic features, we analyzed 402 resected stage III colon carcinomas [191 deficient (d)-MMR; 189 proficient (p)-MMR] from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1,094 p-MMR). Association of morphologic features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazards models were developed to predict TTR. Tumor morphologic features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TIL), high-grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% confidence interval (CI), 1.14–3.57; P = 0.018; 3-year recurrence: 40.2% vs. 20.4%; Q1 vs. Q2–4]. Among d-MMR tumors, extent of inflammatory stroma (continuous HRadj 0.98; 95% CI, 0.96–0.99; P = 0.028; 3-year recurrence: 13.3% vs. 33.4%, Q4 vs. Q1) and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphologic differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis.

Significance:
A deep learning algorithm can quantify tumor morphologic features that may reflect underlying mechanisms driving prognosis within MMR groups. TSR was the most robust morphologic feature associated with TTR in p-MMR colon cancers. Extent of inflammatory stroma and N stage were the strongest prognostic features in d-MMR tumors. TIL density was not independently prognostic in either MMR group.
Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes
Authors: Tao Ran , Dharmavaram Naga , El Shaer Ahmed , Heffernan Shannon , Tu Wanxin , Ma James , Garcia-Arango Mariana , Baber Aurangzeb , Dhingra Ravi , Runo James , Masri S. Carolina , Rahko Peter , Raza Farhan 
Published: May 2024

BACKGROUND:
While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance.

METHODS:
We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves.

RESULTS:

On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48–0.54 versus 0.38) and peak VO
2
percentage predicted (0.23–0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO
2
<50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11–0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16–0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53–1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082).

CONCLUSIONS:
In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.
Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis
Authors: Xiao Feng , Nguyen Ngoc Uyen Nhi , Wang Ping , Li Shujuan , Hsu Ching-Cheng , Thet Suwannee , Kimura Wataru , Luo Xiang , Lam Nicholas T. , Menendez-Montes Ivan , Elhelaly Waleed M. , Cardoso Alisson Campos , Pereira Ana Helena Macedo , Singh Rohit , Sadayappan Sakthivel , Kanchwala Mohammed , Xing Chao , Ladha Feria A. , Hinson J. Travis , Hajjar Roger J. , Hill Joseph A. , Sadek Hesham A. 
Published: May 2024

BACKGROUND:
Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes.

METHODS:
Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo.

RESULTS:
We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in vitro and in vivo identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin.

CONCLUSIONS:
These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.
Raising State Minimum Wages, Lowering Community College Enrollment
Authors: Schanzenbach Diane Whitmore , Turner Julia A. , Turner Sarah 
Published: May 2024

Abstract
Changes in the minimum wage may impact college enrollment and educational attainment. Using institutional data on college enrollment and program completion, we find that enrollment falls markedly among students at public two-year institutions in response to increases in the minimum wage. The largest enrollment effects are seen for those students who are enrolled part-time at community colleges. We find little evidence of negative effects on the attainment of certificates or degrees, suggesting that increases in the minimum wage are unlikely to divert students from degree attainment.