bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-Cell Lymphoma
Authors: Meriranta Leo , Sorri Selma , Huse Kanutte , Liu Xiaonan , Spasevska Ivana , Zafar Sadia , Chowdhury Iftekhar , Dufva Olli , Sahlberg Eerika , Tandarić Luka , Karjalainen-Lindsberg Marja-Liisa , Hyytiäinen Marko , Varjosalo Markku , Myklebust June H. , Leppä Sirpa 
Published: April 2024

Abstract
Pathomechanisms that activate oncogenic B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma (DLBCL) are largely unknown. Kelch-like family member 6 (KLHL6) encoding a substrate-adapter for Cullin-3-RING E3 ubiquitin ligase with poorly established targets is recurrently mutated in DLBCL. By applying high-throughput protein interactome screens and functional characterization, we discovered that KLHL6 regulates BCR by targeting its signaling subunits CD79A and CD79B. Loss of physiologic KLHL6 expression pattern was frequent among the MCD/C5-like activated B-cell DLBCLs and was associated with higher CD79B levels and dismal outcome. Mutations in the bric-a-brac tramtrack broad domain of KLHL6 disrupted its localization and heterodimerization and increased surface BCR levels and signaling, whereas Kelch domain mutants had the opposite effect. Malfunctions of KLHL6 mutants extended beyond proximal BCR signaling with distinct phenotypes from KLHL6 silencing. Collectively, our findings uncover how recurrent mutations in KLHL6 alter BCR signaling and induce actionable phenotypic characteristics in DLBCL.
Significance: Oncogenic BCR signaling sustains DLBCL cells. We discovered that Cullin-3-RING E3 ubiquitin ligase substrate-adapter KLHL6 targets BCR heterodimer (CD79A/CD79B) for ubiquitin-mediated degradation. Recurrent somatic mutations in the KLHL6 gene cause corrupt BCR signaling by disrupting surface BCR homeostasis. Loss of KLHL6 expression and mutant-induced phenotypes associate with targetable disease characteristics in B-cell lymphoma.
See related commentary by Leveille et al.
See related commentary by Corcoran et al.
LP-184, a Novel Acylfulvene Molecule, Exhibits Anticancer Activity against Diverse Solid Tumors with Homologous Recombination Deficiency
Authors: Kulkarni Aditya , Zhou Jianli , Biyani Neha , Kathad Umesh , Banerjee Partha P. , Srivastava Shiv , Prucsi Zsombor , Solarczyk Kamil , Bhatia Kishor , Ewesuedo Reginald B. , Sharma Panna 
Published: April 2024

Abstract

Homologous recombination (HR)-related gene alterations are present in a significant subset of prostate, breast, ovarian, pancreatic, lung, and colon cancers rendering these tumors as potential responders to specific DNA damaging agents. A small molecule acylfulvene prodrug, LP-184, metabolizes to an active compound by the oxidoreductase activity of enzyme prostaglandin reductase 1 (PTGR1), which is frequently elevated in multiple solid tumor types. Prior work demonstrated that cancer cell lines deficient in a spectrum of DNA damage repair (DDR) pathway genes show increased susceptibility to LP-184. Here, we investigated the potential of LP-184 in targeting multiple tumors with impaired HR function and its mechanism of action as a DNA damaging agent. LP-184 induced elevated DNA double-strand breaks in HR deficient (HRD) cancer cells. Depletion of key HR components BRCA2 or ataxia telangiectasia mutated (ATM) in cancer cells conferred up to 12-fold increased sensitivity to the LP-184. LP-184 showed nanomolar potency in a diverse range of HRD cancer models, including prostate cancer organoids, leiomyosarcoma cell lines, and patient-derived tumor graft models of lung, pancreatic, and prostate cancers. LP-184 demonstrated complete, durable tumor regression in 10 patient-derived xenograft (PDX) models of HRD triple-negative breast cancer (TNBC) including those resistant to PARP inhibitors (PARPi). LP-184 further displayed strong synergy with PARPi in ovarian and prostate cancer cell lines as well as in TNBC PDX models. These preclinical findings illustrate the potential of LP-184 as a pan-HRD cancer therapeutic. Taken together, our results support continued clinical evaluation of LP-184 in a large subset of HRD solid tumors.

Significance:
New agents with activity against DDR-deficient solid tumors refractory to standard-of-care therapies are needed. We report multiple findings supporting the potential for LP-184, a novel alkylating agent with three FDA orphan drug designations, to fill this void clinically: strong nanomolar potency; sustained, durable regression of solid tumor xenografts; synthetic lethality with HR defects. LP-184 adult phase IA trial to assess safety in advanced solid tumors is ongoing.
VI Congresso Internacional de Minería, La Minería Hispana e Iberoamericana: Contribución a su Investigación Histórica Estudios Fuentes Bibliografía
Authors: Portal Maria da Glória Alves 
Published: April 2024

(1º parágrafo da resenha)
O VI Congresso Internacional de Mineração, reunido em Mad í em junho de 1970, foi precedido de um Colóquio Internacional sobre História da Mineração, organizado pela “Cátedra de San Isidoro de León”.
Trends Favoring an Anatomical Approach to Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating From the Left Ventricular Summit
Authors: Yamada Takumi , Kay George Neal 
Published: April 2024

BACKGROUND:
Epicardial radiofrequency catheter ablation (RFCA) of idiopathic ventricular arrhythmias (VAs) originating from the left ventricular summit (LVS) is challenging because of the anatomic barriers. On the other hand, RFCA at the endocardial sites near the earliest epicardial activation site of LVS-VAs (anatomic approach) has proven successful. The evolving trends in the approaches and outcomes of RFCA of LVS-VAs at a single center were evaluated.

METHODS:
We studied 88 consecutive patients with idiopathic LVS-VAs at our institute from 2009 to 2019. These patients were divided into 3 periods: 2009 to 2012 (early), 2013 to 2015 (middle), and 2016 to 2019 (recent). The data were compared among the 3 periods.

RESULTS:

The RFCA success rate did not significantly change from the early to middle period but significantly increased from the middle to recent period (
P
=0.0315). The transpericardial approach usage significantly decreased over the 3 periods. The anatomic approach usage significantly increased over the 3 periods. The use of the transpericardial approach did not affect the RFCA outcomes over the 3 periods. The success rate of the anatomic RFCA tended to increase from the early to middle period and significantly increased from the middle to recent period (
P
=0.0412). The number of endocardial locations where RFCA was successful increased over the 3 periods.

CONCLUSIONS:
Over the 10-year period, the transpericardial approach became decreasingly performed, whereas the anatomic approach became increasingly performed with a satisfactory improvement in the RFCA outcomes of LVS-VAs. The anatomic RFCA became more successful by identifying more and various endocardial locations as target sites.
Prognostic Impact of Left Atrial Appendage Patency After Device Closure
Authors: Chen Mu , Yao Peng-Cheng , Fei Zhen-Tao , Wang Qun-Shan , Yu Yi-Chi , Zhang Peng-Pai , Li Wei , Zhang Rui , Mo Bin-Feng , Zhao Ming-Zhe , Yu Yi , Yang Mei , Zhao Yan , Gong Chang-Qi , Sun Jian , Li Yi-Gang 
Published: April 2024

BACKGROUND:
The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post–LAA closure in patients with atrial fibrillation, remains elusive.

METHODS:
Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency.

RESULTS:

Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post–LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787–1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17–8.83];
P
=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06–1.17];
P
=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29–10.42];
P
=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71–8.07];
P
=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28–10.09];
P
=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%;
P
=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%;
P
=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%;
P
=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency.

CONCLUSIONS:
LAA patency detected by cardiac computed tomography angiography at 3 months post–LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03788941.
Disentangling North Atlantic Ocean–Atmosphere Coupling Using Circulation Analogs
Authors: Patterson Matthew , O’Reilly Christopher , Robson Jon , Woollings Tim 
Published: April 2024

Abstract
The coupled nature of the ocean–atmosphere system frequently makes understanding the direction of causality difficult in ocean–atmosphere interactions. This study presents a method to decompose turbulent surface heat fluxes into a component which is directly forced by atmospheric circulation and a residual which is assumed to be primarily “ocean-forced.” This method is applied to the North Atlantic in a 500-yr preindustrial control run using the Met Office’s HadGEM3-GC3.1-MM model. The method shows that atmospheric circulation dominates interannual to decadal heat flux variability in the Labrador Sea, in contrast to the Gulf Stream where the ocean primarily drives the variability. An empirical orthogonal function analysis identifies several residual heat flux modes associated with variations in ocean circulation. The first of these modes is characterized by the ocean warming the atmosphere along the Gulf Stream and North Atlantic Current and the second by a dipole of cooling in the western subtropical North Atlantic and warming in the subpolar North Atlantic. Lead–lag regression analysis suggests that atmospheric circulation anomalies in prior years partly drive the ocean heat flux modes; however, there is no significant atmospheric circulation response in years following the peaks of the modes. Overall, the heat flux dynamical decomposition method provides a useful way to separate the effects of the ocean and atmosphere on heat flux and could be applied to other ocean basins and to either models or reanalysis datasets.

Significance Statement
Variability of the ocean affects atmospheric circulation and provides a source of long-term predictability for surface weather. However, the atmosphere also affects the ocean. This makes the separation of cause and effect in such atmosphere–ocean interactions difficult. This paper introduces a method to separate “turbulent heat fluxes,” the primary means by which the atmosphere and ocean influence one another, into a component driven by atmospheric variability and a component which is primarily related to ocean variability. The method is tested by applying it to a climate model simulation and is able to identify regions in which the exchange of heat between the ocean and atmosphere is dominated by atmospheric variability and regions which are dominated by the ocean.
Continuous Peak Period Estimates from Discrete Surface-Wave Spectra
Authors: Smit Pieter B. , Egan Galen , Houghton Isabel A. 
Published: April 2024

Abstract
Peak periods estimated from finite-resolution frequency spectra are necessarily discrete. For wind-generated surface gravity waves, conflicting considerations of robust (quasi)-stationary statistics, and high spectral resolution, combined with the inverse relation between frequency and period, this typically implies that swell periods (above 10 s) are resolved at best at s intervals. Here, we consider a method to improve peak period estimates for finite-resolution spectra. Specifically, we propose to define the peak period based on continuous spectra derived from a spline-based interpolation of the discretely sampled monotone cumulative distribution function. The method may directly be applied to existing discrete spectra—the original time-domain data (which may not be available) are not required. We compare reconstructed spectra and derived peak periods to parametric shapes and field data. Peak estimates are markedly improved, allowing for better tracking of, e.g., swells. The proposed method also marginally improves spectral levels and shape for a given discretely sampled estimate.
Increasing Underrepresented Minority Representation in a General Surgery Residency Program Utilizing a 3-Phase Strategy
Authors: Magura Connor M. , Rubino Matthew S. , Bolaji Toba , Goldberg Michael B. 
Published: April 2024

Background Underrepresented minority groups (URMs) in surgery are not significantly increasing despite evidence suggesting that diversity in health care providers leads to excellent patient outcomes and care. Efforts to increase URM representation in surgical residency programs are essential for addressing disparities and improving health care delivery. Methods This retrospective study outlines a three-phase strategy implemented at a large academic-affiliated hospital to increase URM representation in its general surgery residency program. The strategy encompassed interview selection with a holistic review and implicit bias training for interviewers, modification of the interview scoring rubric, and post-interview recruitment efforts, including a virtual second look event for URM applicants. Results Following the implementation of these strategies, the URM match rate improved from 0 to 33.3% in the first year and was sustained at 33.3% in the subsequent year. Consequently, the representation of URMs in the residency program rose from 6.7% before our intervention to 13.3% afterwards. Discussion This structured approach successfully increased URM representation in a surgical residency program, affirming the success of targeted recruitment strategies. By promoting a diverse and inclusive environment, the program better reflects the community it serves, with aims at improved patient care and patient satisfaction.
Income Shock and Child Labour: Revisiting the Poverty Link
Authors: Chowdhury Sahana Roy , Ghosh Dona 
Published: April 2024

The COVID-19 pandemic has triggered massive supply chain disruptions, job losses and income shocks at the micro-level. This has repercussions on the labour market outcomes not only at the macro-level but also at the micro-level labour supply decisions. This article provides a theoretical model of the impact of such recessionary income shocks on household’s child labour (CL) decision. CL has been a major concern for the developing world, especially for India with its goal towards ‘inclusive growth’. Parental altruism and choice of substituting CL income by their own are endogenous. Interestingly, income shocks have ambiguous effect on CL in general, but they have a clear positive impact on regions with high cost of living. When wages are inflexible, such shocks, depending upon their extent, might be CL-inducing as well as poverty-enhancing. It infers that any in-kind transfer or policies such as mid-day meal that essentially reduces cost of living is always CL-reducing. JEL Codes: J13, J29, D10
The outcome of endovenous intervention for acute iliofemoral deep venous thrombosis with and without inferior vena cava filter
Authors: Alhewy Mohammed Alsagheer , Hanbal Ibrahim Hanbal , Abdelhafez Abdelaziz Ahmed , Metwaly Mohamed Hamza , Abdelmohsen Abdelhalim A , Ghazala Ehab Abd elmoneim , Khedr Alhussein M , Khamis Ahmed Atef , Gado Hassan , Abd-Elgawad Wael Abdo Abdo , El Sayed Abdullah , Ibrahim Awad , Elghoneimy Yasser , Elimam Sameh E 
Published: April 2024

Background Catheter-directed thrombolysis (CDT) for acute iliofemoral deep venous thrombosis (DVT) is an endovenous interventional therapy that can quickly remove the acute thrombus, thereby improving the clinical outcomes of proximal DVT. However, instrumentation of extensive fresh thrombus may be associated with iatrogenic pulmonary embolism (PE). Therefore, we aimed to compare CDT’s safety, complications, and perioperative embolic (PE) insults for acute iliofemoral DVT, with and without an IVC filter. Methods One hundred twenty patients having acute proximal DVT for less than 14 days and undergoing endovenous therapy were included and presented to the vascular surgery department of Al-Azhar University Hospitals, Egypt. The patients were randomized into two equal groups, Groups A and B, each having 60 patients. Group A was treated with IVC filter insertion, while Group B was treated without a filter. The anticoagulation and CDT procedures were similar between the two groups. Results The sample included 96 females (80%) and 24 males (20%), with a mean age of 32.6 ± 7.2 years. Clinically no clinical PE occurred in both groups. However, radiologically, new lesions in multislice CT pulmonary angiogram and V/Q scan were noted in two of 60 patients (3.33%) of the IVC filter group, compared with three patients (5 %) in the non-filtered group. Conclusion Endovenous intervention in the form of CDT for acute iliofemoral DVT without an IVC filter is safe and not associated with an increased risk of pulmonary embolization than filter usage. The routine use of IVC filters should not be used mandatorily during CDT.
Influence of Three Different Vertical Positions of MARPE Expander on Maxillofacial Complex: A Finite Element Analysis
Authors: Rai Priyank , Gupta Veenita , Tripathi Tulika , Kanase Anup 
Published: April 2024

Objective The study was conducted to analyze the stress distribution and displacement due to three different vertical positions of the mini-implant assisted rapid palatal expansion (MARPE) appliance. Methods A three-dimensional finite element meshed model was created of the maxillofacial complex with the help of cone beam computed tomography (CBCT) digital imaging and communication in medicine (DICOM) data of a patient with transverse maxillary deficiency using materialise interactive medical image control system (MIMICS) software. Three different groups with varying expander heights were used to study the expansion effects on the maxillofacial structures. von Mises stress and displacement at various skeletal and dental points were evaluated using ANSYS software. Results In the midpalatal suture, the posterolateral portion of the hard palate and the maxillary and pterygoid bones showed the greatest amount of stress distribution and displacement pattern. Group 1 showed the maximum amount of transverse displacement compared to groups 2 and 3. Sagittally, all the teeth had a forward displacement. Vertically, groups 2 and 3 showed clockwise rotation of the occlusal plane, while all teeth showed downward displacement in group 1. Conclusion In conclusion, a V-shaped expansion in the maxilla with a superior and posterior vertex was noted. Group 1, that is, appliance placed in close approximation to the palate, showed greater displacement compared to groups 2 and 3.
Impact of Delirium Onset and Duration on Mortality in Patients With Cancer Admitted to the ICU
Authors: Tao Jing , Seier Kenneth P. , Chawla Sanjay , Tan Kay See , Wheeler Amanda , Sanzone Joanna , Marasigan-Stone Carina B. , Simondac Justina-Sheila S. , Pascual Analin V. , Kostelecky Natalie T. , Voigt Louis P. 
Published: April 2024

Background Little is known on the effects of delirium onset and duration on outcome in critically ill patients with cancer. Objectives To determine the impact of delirium onset and duration on intensive care unit (ICU) and hospital mortality and length of stay (LOS) in patients with cancer. Methods Of the 915 ICU patients admitted in 2018, 371 were included for analysis after excluding for terminal disease, <24-h ICU stay, lack of active cancer and delirium. Delirium was defined as early if onset was within 2 days of ICU admission, late if onset was on day 3 or later, short if duration was 2 days or less, and long if duration was 3 days or longer. Patients were placed into 4 combination groups: early-short, early-long, late-short, and late-long delirium. Multivariate analysis controlling for sex, age, metastatic disease, and predelirium hospital LOS was performed to determine ICU and hospital mortality and LOS. Exploratory analysis of long-term survival was also performed. Restricted cubic splines were performed to confirm the use of 2 days to distinguish between early versus late onset and short versus long duration. Results A total of 32.9% (n = 122) patients had early-short, 39.1% (n = 145) early-long, 16.2% (n = 60) late-short, and 11.9% (n = 44) late-long delirium. Late-long delirium was independently associated with increased ICU (OR 4.45, CI 1.92-10.30; P < .001) and hospital (OR 2.91, CI 1.37-6.19; P = .005) mortality and longer ICU (OR 1.97, CI 1.58-2.47; P < .001) LOS compared to early-short delirium. Early delirium had better overall survival at 18 months than late delirium. Long-term survival further improved when delirium duration was 2 days or less. Prediction heatmaps confirm the use of a 2-day cutoff. Conclusion Late delirium, especially with long duration, significantly worsens outcome in ICU patients with cancer and should be considered a harbinger of poor overall condition.
Machinability of wood-plastic composites from the CNC milling process using the Box-Behnken design and response surface methodology for building applications
Authors: Homkhiew Chatree , Cheewawuttipong Watthanaphon , Srivabut Chainarong , Boonchouytan Worapong , Rawangwong Surasit 
Published: April 2024

This research investigated the optimization of CNC milling parameters on hardness and surface roughness properties resulting from variations in speed (220, 470, and 720 rpm), feed rate (200, 300, and 400 mm/min), and depth of cut (3, 5, and 7 mm) based on experimental design. This study aimed to evaluate the effects and relation of milling parameters using different end mill diameters (8 and 12 mm) for machining wood-plastic composites (WPCs). All of the experimental runs were determined by the Box-Behnken design and optimized using the response surface methodology. The findings from this study revealed that the main milling parameters significantly affected the hardness, average roughness ( Ra), and mean peak-to-valley height ( Rz) of the WPCs. Increasing the speed in a range from 220 to 720 rpm resulted in higher hardness values. On the other hand, the Ra and Rz was decreased. Additionally, this experimental result is different from the morphological structure and surface observation. It was seen that the CNC milling conditions using high speed at 720 rpm displayed smooth surfaces, which resulted in visible evenness on the WPC surfaces. Finally, numerical optimization is a good technique for the experimental results and the predicted values. The predicted conditions for the CNC milling process using end mill diameters of 8 and 12 mm included a speed of 720 rpm, a feed rate of 300 mm/min, and a depth of cut of 3 mm with the best desirability of 0.973 (97.30%). These conditions were verified in the response models and confirmed the optimal values from observed values for the variables included in the models. Also, these optimal conditions for the CNC milling parameters can be used on other types of WPCs with melting points of plastic higher than 180°C.