bluuebunny/crossref_metadata_2025_split huggingface dataset:
291. TREATMENT OUTCOMES ACCORDING TO PATHOLOGICAL RESPONSE AFTER NEOADJUVANT CHEMORADIATION AND SURGEY IN OESOPHAGEAL CANCER
Authors: Anap Yogesh , Pawar Suraj 
Published: August 2023

Abstract

Background
Neoadjuvant chemoradiation followed by surgery is now standard of care for resectable oesophageal cancer. The aim of this study was to analyse various parameters of treatment outcome with respect to pathologic complete responders (pCR) and pathological partial responders.

Methods
Consecutive 136 patients with operable oesophageal cancer, who received neoadjuvant chemoradiation followed by oesophageal surgery between march 2013 to january 2023 were included. Data was extracted from electronically and physically maintained patient clinical records. Data was collected in mircosoft excel and analysed using Epi Info Version 7.2. Chi square test and student t test were used to test the difference between proportions and means respectively. All tests were 2 tailed and significance level was 0.05. Various demographic, clinical and treatment outcome parameters were analysed according to pathological complete responders (pCR) and pathological partial responders.

Results
Out of 136 patients, 112(82.3%) had squamous histology. Among 136 patients, 75(55%)had pCR. Postoperative complications were seen in 30(49.18%) of pCR group as compared to 24(32%) in partial responders (p = 0.04). Pulmonary 16(53%) vs 8(33%), cardiac 5(16%) vs 3(12%) and vocal cord palsy 6(20%) vs 8(32%) complications were seen in pCR vs partial responders respectively. 9(14.75%) of pCR group had recurrences as compared to 32(45.33%) in partial responders (p = 0.003). pCR group had distant recurrences in neck 4(66.6%) (p = 0.01) and liver 4(66%) as compared to 2(14.3%) and 4(28.5%) respectively in partial responders.

Conclusion
High pCR is seen due to more number of patients with squamous histology. pCR has more postoperative pulmonary and cardiac complications which may indicate inherent radiosensitivity and tissue fragility which mandates strict ERAS program and affirms deferred surgery and wait and watch policy for complete clinical responders. Recurrences in pCR are less but are seen mostly in distant sites indicating aggressive surveillance protocol.
337. PREDICTION OF PULMONARY METASTASIS IN ESOPHAGEAL CARCINOMA PATIENTS WITH INDETERMINATE
Authors: Chen Maohui , Bin Zheng , Hongjin Wang , Yizhou Huang , Shuliang Zhang , Taidui Zeng , Chun Chen 
Published: August 2023

Abstract

Background
Indeterminate pulmonary nodules (IPNs) are common after surgery for esophageal cancer. The paucity of data on postoperative IPNs for esophageal cancer causes a clinical dilemma.

Objective
The aim of this study was to identify the characteristics and clinical significance of IPNs after radical esophagectomy for metastatic esophageal cancer and determine the risk factors for pulmonary metastasis and construct a risk score model to standardize the appropriate time to either follow up or treat the patient.

Methods
All consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between 2013 and 2016 were included in this retrospective study. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop risk score models.

Results
A total of 816 patients were enrolled in the study. During a median follow-up period of 45 months, IPNs were detected in 221 (27.1%) patients, of whom 66 (29.9%) were diagnosed with pulmonary metastases. The following five variables maintained prognostic significance after multivariate analyses: the pathologic N category, number of IPNs, shape of IPNs, time of detection of IPNs, and size of IPNs. The Pulmonary Metastasis Prediction Model (PMPM) scale ranges from 0 to 15 points and patients with higher scores have a higher probability of pulmonary metastases. After validated, the PMPM scale showed good discrimination with an AUC of 0.939.

Conclusion
A PMPM scale for IPNs in patients who underwent esophagectomy for ESCC may be clinically useful for diagnostic and therapeutic decision-making.
384. ROBUST CULTURE OF PATIENT-DERIVED ESOPHAGEAL ADENOCARCINOMA ORGANOIDS OF SINGLE CELL LINEAGE
Authors: Naeem Mansur , Shathasivam Premalatha , Rispoli Thaiane , Akhter Akhi , Aiyar Niharikaa , Wilson Gavin , Yeung Jonathan 
Published: August 2023

Abstract

Background
Esophageal adenocarcinoma (EAC) has a high mutational rate leading to significant intratumoral heterogeneity. We have previously generated patient-specific organoid models of EAC from endoscopic biopsies and resection specimens. It is unclear whether intratumoral heterogeneity is retained in these organoid models, but we did observe morphologic heterogeneity in these organoid cultures. In this study, we sought to generate methods to isolate clonal organoids from patient-derived EAC organoid cultures.

Methods
Patient derived EAC organoids were resuspended into single cell solution and dead cells were stained with DAPI. Automatic cell sorter was used to pipette a single live cell into Matrigel coated 96 well plate. Single cell per well was pipetted and checked within 24 hours using light microscope. Cells were coated with a second coat of Matrigel and media and allowed to grow into full size organoids. Organoids of single morphology were expanded and collected for further analysis.

Results
We have established a high-throughput method to culture patient-derived organoids deriving from a single cell, allowing for lineage analysis. Organoids grown from a single cell take up to 21 days to grow to a full-sized organoid of distinct morphology. We identified 4 distinct EAC organoid morphologies which we have designated: solid, cystic, budding, and grape.

Conclusion
Isolating EAC organoid morphology is the first step in studying inter- and intra- tumour heterogeneity in EAC organoids. This method allows for studying morphology-transcriptome and morphology-drug response correlations.
Was Spanish debt sustainable? A debt sustainability analysis between 1850 and 1913
Authors: Roldan Alba 
Published: August 2023

Abstract
At the end of the nineteenth century, Spain suffered from constant budget deficits. This article seeks to establish whether the Spanish debt was sustainable or not between 1850 and 1913 and how debt sustainability changed due to the various policies implemented by policymakers. This paper sheds new light on the analysis of Spanish fiscal solvency by estimating Bohn’s test (fiscal reaction function). The results are interpreted using narrative evidence and data from previous studies. The findings reveal that Spanish debt was unsustainable between 1850 and 1902 while the debt restructuring of Raimundo Fernández Villaverde made the Spanish public debt sustainable from 1902.
Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial
Authors: Ghazi Lama , Yamamoto Yu , Fuery Michael , O’Connor Kyle , Sen Sounok , Samsky Marc , Riello Ralph J , Dhar Ravi , Huang Joanna , Olufade Temitope , McDermott James , Inzucchi Silvio E , Velazquez Eric J , Wilson Francis Perry , Desai Nihar R , Ahmad Tariq 
Published: August 2023

AbstractBackground and AimsPatients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF.MethodsPragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge.ResultsThousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on β-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT.ConclusionsA real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure.
Determinants of acute irreversible electroporation lesion characteristics after pulsed field ablation: the role of voltage, contact, and adipose interference
Authors: Gasperetti Alessio , Assis Fabrizio , Tripathi Hemantkumar , Suzuki Masahito , Gonuguntla Akhilesh , Shah Rushil , Sampognaro James , Schiavone Marco , Karmarkar Parag , Tandri Harikrishna 
Published: August 2023

Abstract

Aims
Pulsed field ablation (PFA) is a non-thermal ablative approach in which cardiomyocyte death is obtained through irreversible electroporation (IRE). Data correlating the biophysical characteristics of IRE and lesion characteristics are limited. The aim of this study was to assess the effect of different procedural parameters [voltage, number of cycles (NoCs), and contact] on lesion characteristics in a vegetal and animal model for IRE.

Methods and results
Two hundred and four Russet potatoes were used. Pulsed field ablation lesions were delivered on 3 cm cored potato specimens using a multi-electrode circular catheter with its dedicated IRE generator. Different voltage (from 300 to 1200 V) and NoC (from 1 to 5×) protocols were used. The impact of 0.5 and 1 mm catheter-to-specimen distances was tested. A swine animal model was then used to validate the results observed in the vegetable model. The association between voltage, the NoCs, distance, and lesion depth was assessed through linear regression. An almost perfect linear association between lesion depth and voltage was observed (R2 = 0.95; P &lt; 0.001). A similarly linear relationship was observed between the NoCs and the lesion depth (R2 = 0.73; P &lt; 0.001). Compared with controls at full contact, a significant dampening on lesion depth was observed at 0.5 mm distance (1000 V 2×: 2.11 ± 0.12 vs. 0.36 ± 0.04, P &lt; 0.001; 2.63 ± 0.10 vs. 0.43 ± 0.08, P &lt; 0.001). No lesions were observed at 1.0 mm distance.

Conclusion
In a vegetal and animal model for IRE assessment, PFA lesion characteristics were found to be strongly dependent on voltage settings and the NoCs, with a quasi-linear relationship. The lack of catheter contact was associated with a dampening in lesion depth.
Performance of a multi-sensor implantable defibrillator algorithm for heart failure monitoring in the presence of atrial fibrillation
Authors: Boriani Giuseppe , Bertini Matteo , Manzo Michele , Calò Leonardo , Santini Luca , Savarese Gianluca , Dello Russo Antonio , Santobuono Vincenzo Ezio , Lavalle Carlo , Viscusi Miguel , Amellone Claudia , Calvanese Raimondo , Santoro Amato , Rapacciuolo Antonio , Ziacchi Matteo , Arena Giuseppe , Imberti Jacopo F , Campari Monica , Valsecchi Sergio , D’Onofrio Antonio 
Published: August 2023

Abstract

Aims
The HeartLogic Index combines data from multiple implantable cardioverter defibrillators (ICDs) sensors and has been shown to accurately stratify patients at risk of heart failure (HF) events. We evaluated and compared the performance of this algorithm during sinus rhythm and during long-lasting atrial fibrillation (AF).

Methods and results
HeartLogic was activated in 568 ICD patients from 26 centres. We found periods of ≥30 consecutive days with an atrial high-rate episode (AHRE) burden &lt;1 h/day and periods with an AHRE burden ≥20 h/day. We then identified patients who met both criteria during the follow-up (AHRE group, n = 53), to allow pairwise comparison of periods. For control purposes, we identified patients with an AHRE burden &lt;1 h throughout their follow-up and implemented 2:1 propensity score matching vs. the AHRE group (matched non-AHRE group, n = 106). In the AHRE group, the rate of alerts was 1.2 [95% confidence interval (CI): 1.0–1.5]/patient-year during periods with an AHRE burden &lt;1 h/day and 2.0 (95% CI: 1.5–2.6)/patient-year during periods with an AHRE-burden ≥20 h/day (P = 0.004). The rate of HF hospitalizations was 0.34 (95% CI: 0.15–0.69)/patient-year during IN-alert periods and 0.06 (95% CI: 0.02–0.14)/patient-year during OUT-of-alert periods (P &lt; 0.001). The IN/OUT-of-alert state incidence rate ratio of HF hospitalizations was 8.59 (95% CI: 1.67–55.31) during periods with an AHRE burden &lt;1 h/day and 2.70 (95% CI: 1.01–28.33) during periods with an AHRE burden ≥20 h/day. In the matched non-AHRE group, the rate of HF hospitalizations was 0.29 (95% CI: 0.12–0.60)/patient-year during IN-alert periods and 0.04 (95% CI: 0.02–0.08)/patient-year during OUT-of-alert periods (P &lt; 0.001). The incidence rate ratio was 7.11 (95% CI: 2.19–22.44).

Conclusion
Patients received more alerts during periods of AF. The ability of the algorithm to identify increased risk of HF events was confirmed during AF, despite a lower IN/OUT-of-alert incidence rate ratio in comparison with non-AF periods and non-AF patients.

Clinical Trial Registration
http://clinicaltrials.gov/Identifier: NCT02275637
Mapping structures on the core–mantle boundary using Sdiff postcursors: Part I. Method and Validation
Authors: Martin Carl , Bodin Thomas , Cottaar Sanne 
Published: August 2023

SUMMARY
Ultra-low velocity zones (ULVZs) are patches of extremely slow seismic velocities on the core–mantle boundary (CMB). Here, we target them using the postcursors to S core-diffracted phases (Sdiff) caused by ULVZs. We use traveltimes of these postcursors to make probabilistic maps using a reversible-jump Markov chain Monte Carlo inversion setup. For the forward model, we extend 2-D wave front tracking (2DWT) software, previously developed for surface wave multipathing studies, to the CMB. The 2DWT is able to model the full multipathing behaviour of Sdiff postcursors and compute arrival times for a given ULVZ input velocity structure on the order of a few CPU seconds, as opposed to 100s of CPU hours required for 3-D full waveform synthetics. We validate the method using synthetic data sets produced by the 2DWT, as well as 3-D full waveform synthetics, using a parametrisation formed from a collection of ellipses. We also test idealistic data coverage versus a case of more realistic coverage. We show ULVZ size and velocity reduction can typically be well recovered, and our maps show the inherent trade-off between these parameters around the edge of the ULVZ. Our method cannot directly constrain ULVZ height; tests show that it underestimates ULVZ velocity reductions and overestimates ellipticity for thinner ULVZs due to neglecting mantle effects.
Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X
Authors: Mention Karen , Cavusoglu-Doran Kader , Joynt Anya T , Santos Lúcia , Sanz David , Eastman Alice C , Merlo Christian , Langfelder-Schwind Elinor , Scallan Martina F , Farinha Carlos M , Cutting Garry R , Sharma Neeraj , Harrison Patrick T 
Published: August 2023

Abstract
Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G&gt;A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23–27 (SE23–27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and restored protein expression. However, bystander editing at the adjacent adenine (c.3847A&gt;G), caused an amino acid change (R1283G) that affects CFTR maturation and ablates ion channel activity. In primary human nasal epithelial cells homozygous for W1282X, ABE corrected 27% of alleles, but with a notably lower level of bystander editing, and CFTR channel function was restored to 16% of wild-type levels. Using the HITI approach, correct integration of a SE23–27 in intron 22 of the CFTR locus in 16HBEge W1282X cells was detected in 5.8% of alleles, resulting in 7.8% of CFTR transcripts containing the SE23–27 sequence. Analysis of a clonal line homozygous for the HITI-SE23–27 produced full-length mature protein and restored CFTR anion channel activity to 10% of wild-type levels, which could be increased three-fold upon treatment with the triple combination of CF modulators. Overall, these data demonstrate two different editing strategies can successfully correct W1282X, the second most common class I variant, with a concomitant restoration of CFTR function.
What drives network evolution? Comparing R&D project and patent networks in the EU
Authors: Akçomak İbrahim Semih , Çetinkaya Umut Yılmaz , Erdil Erkan , Gossart Müge Özman 
Published: August 2023

Abstract
Collaboration networks are the main mechanisms through which regional innovation capacities are enhanced. These networks have been analyzed by using data either on research projects or patents. However, analyzing only one type of network can limit our understanding of regional innovation dynamics. In this paper, we investigate the drivers of network evolution in two inter-regional network types within the European Union: R&D project networks and co-patenting networks. Specifically, we examine data on Framework Program project collaborations and patent collaborations at the NUTS2 regional level between 2011 and 2019. Our empirical strategy is based on Stochastic Actor-Oriented Model where we analyze and compare the factors that affect the evolution of two networks. We find that path-dependent processes resulting from past networks, such as triadic closure, preferential attachment, and tie repetition, play a more important role in explaining the evolution of R&D project networks compared with patent networks. On the other hand, regional characteristics, particularly the patenting intensity of a region and similarity in patenting between regions appear to be more influential in shaping patent networks. These results have important implications for the future evolution of knowledge networks in Europe.
Trajectories of kidney function and risk of mortality
Authors: van der Burgh Anna C , Sedaghat Sanaz , Ikram M Arfan , Hoorn Ewout J , Chaker Layal 
Published: August 2023

Abstract

Background
We aimed to identify patterns within the rate of kidney function decline, determinants of these patterns and their association with all-cause mortality risk in the general population.

Methods
Participants aged ≥ 45 years with at least one assessment of creatinine-based estimated glomerular filtration rate (eGFR) taken between 1997 and 2018 were selected from a population-based cohort study. Analyses were performed using several distinct latent class trajectory modelling methods. Cumulative incidences were calculated with 45 years of age as the starting point.

Results
In 12 062 participants (85 922 eGFR assessments, mean age 67.0 years, 58.7% women, median follow-up 9.6 years), four trajectories of eGFR change with age were identified: slow eGFR decline [rate of change in mL/min/1.73 m2 per year (RC), –0.9; 95% CI, –0.9 to –0.9; reference group], intermediate eGFR decline (RC, –2.5; 95% CI, –2.7 to –2.5) and fast eGFR decline (RC, –4.3; 95% CI, –4.4 to –4.1), and an increase/stable eGFR (RC, 0.3; 95% CI, 0.3 to 0.4). Women were more likely to have an increase/stable eGFR [odds ratio (OR), 1.94; 95% CI, 1.53 to 2.46] whereas men were more likely to have a fast eGFR decline (OR, 1.86; 95% CI, 1.33 to 2.60). Participants with diabetes, cardiovascular disease (CVD) or hypertension were more likely to have an intermediate or fast eGFR decline. All-cause mortality risks (cumulative incidence at age of 70 years) were 32.3% (95% CI, 21.4 to 47.9, slow eGFR decline), 6.7% (95% CI, 3.5 to 12.4, intermediate eGFR decline), 68.8% (95% CI, 44.4 to 87.8, fast eGFR decline) and 9.5% (95% CI, 5.5 to 15.7, increase/stable eGFR).

Conclusion
Sex, hypertension, diabetes and CVD were identified as trajectory membership determinants. Having fast eGFR decline was associated with the highest risk of all-cause mortality, highlighting the need for extensive monitoring and prevention of kidney function decline in individuals at risk of having fast eGFR decline.
Characterizing Boundedness of Metaplectic Toeplitz Operators
Authors: Coburn Lewis , Hitrik Michael , Sjöstrand Johannes 
Published: August 2023

Abstract
We study Toeplitz operators on the Bargmann space, with Toeplitz symbols given by exponentials of complex quadratic forms. We show that the boundedness of the corresponding Weyl symbols is necessary for the boundedness of the operators, thereby completing the proof of the Berger–Coburn conjecture in this case. We also show that the compactness of such Toeplitz operators is equivalent to the vanishing of their Weyl symbols at infinity.
Immune Status and SARS-CoV-2 Viral Dynamics
Authors: Li Yijia , Moser Carlee , Aga Evgenia , Currier Judith S , Wohl David A , Daar Eric S , Ritz Justin , Greninger Alexander L , Sieg Scott , Parikh Urvi M , Coombs Robert W , Hughes Michael D , Eron Joseph J , Smith Davey M , Chew Kara W , Li Jonathan Z ,   for the ACTIV-2/A5401 Study Team, Hosey Lara , Roa Jhoanna , Patel Nilam , Degli-Angeli Emily , Goecker Erin , Daza Glenda , Harb Socorro , Dragavon Joan , Aldrovandi Grace , Murtaugh William , Cooper Marlene , Gutzman Howard , Knowles Kevin , Bowman Rachel , Erhardt Bill , Warring Lorraine , Hessinger Diane , Adams Stacey 
Published: August 2023

Abstract
Immunocompromised individuals are disproportionately affected by severe coronavirus disease 2019, but immune compromise is heterogenous, and viral dynamics may vary by the degree of immunosuppression. In this study, we categorized ACTIV-2/A5401 participants based on the extent of immunocompromise into none, mild, moderate, and severe immunocompromise. Moderate/severe immunocompromise was associated with higher nasal viral load at enrollment (adjusted difference in means: 0.47 95% confidence interval, .12–.83 log10 copies/mL) and showed a trend toward higher cumulative nasal RNA levels and plasma viremia compared to nonimmunocompromised individuals. Immunosuppression leads to greater viral shedding and altered severe acute respiratory syndrome coronavirus 2 viral decay kinetics.
Clinical Trials Registration. NCT04518410.