bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of positive resection margins (R1) on long-term survival of patients with advanced diffuse type gastric cancer
Authors: Gaspar-Figueiredo S , Joliat G-R , Borgstein A B J , Van Berge Henegouwen M I , Brunel C , Demartines N , Allemann P , Schäfer M 
Published: June 2022

Abstract

Objective
Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Diffuse type GC have a much worse prognosis compared to intestinal type GC. There is an ongoing debate whether microscopic involvement of the proximal margin (R1 resection) influences overall survival (OS) in advanced gastric cancer.
The aim of this study was to assess OS in patients with diffuse gastric cancers and positive lymph node involvement who underwent oncological gastrectomy with R0 and R1 resections.

Methods
All consecutive patients from two tertiary centers operated with curative intent for diffuse gastric cancer between January 2005 and December 2018 were analyzed. Patients with R2 resections or missing data were excluded. Extracted data included demographics, major comorbidities, ASA score, neo-adjuvant treatment, pre- and postoperative staging (TNM 8th edition), postoperative complication with grading according to Clavien classification, survival data and pattern of recurrence. Lymph node involvement was based on pathology.
Kaplan-Meier curves with log-rank test for comparison were used to evaluate survival between groups.

Results
A total of 94 patients with diffuse gastric cancer were included. Two patients were excluded because of R2 resection and missing data regarding pathology, leaving a cohort of 92 patients (48 male, 44 female, median age 62 years). Sixty-four patients were lymph node positive (pN+); 48 patients (75%) with R0 resection and 16 patients (25%) with R1 resection. No difference in terms of preoperative data and intraoperative characteristics was found between R0 and R1 groups. Median OS was better in the R0 group (27 months, 95% CI 17–37) compared to R1 group (7 months, 95% CI 3–11, p&lt;0.001). Similar results were found with disease-free survival (DSF) (25 vs. 6 months, p=0.002).
On multivariable analysis, T stage and resection margin (R status) were independent factors predicting OS (T stage: HR 4.5, p&lt;0.001, R status: HR 4.2, p&lt;0.001) and DFS (T stage: HR 2.9, p=0.004, R status: HR 3.5, p=0.001) in the cohort of patients with lymph node involvement.

Conclusion
The present series confirmed that patients with negative surgical margins have better OS compared to patients with positive margins in case of locally advanced diffuse GC. Therefore, R0 resections should be the goal of oncological gastrectomies.
Temporal validation of a prognostic model for mortality of patients with AAA treated with EVAR
Authors: Meuli L , Stefanikova S , Menges A-L , Reutersberg B , Zimmermann A , Makaloski V 
Published: June 2022

Abstract

Objective
The role of EVAR in patients with asymptomatic AAA not suitable for open surgical repair has been questioned. The aim of this study was to temporally validate a previously published predictive model for survival after EVAR in asymptomatic AAA.

Methods
This retrospective observational cohort study included all consecutive patients treated with standard EVAR for asymptomatic AAA at a tertiary center between 2001 and 2020.
A predictive Cox model for survival after EVAR in patients treated between 2001 and 2012 (Cohort A) has been published but not yet implemented. Older age, lower eGFR, and COPD were found to be independent predictors for worse survival after EVAR. This Cox model was temporally validated using patients treated at the same institution between 2013 and 2020 (Cohort B) and then updated using the overall cohort. A risk score with four different risk groups was built to predict the 5-year survival and internally validated with resampling methods.

Results
A total of 558 patients (91.2% males, mean age 74.9 years) were treated for asymptomatic AAA with EVAR. At 5 years, mortality was 35.9% in Cohort A, and 36.2% in Cohort B, p=.102 (log-rank). The original model based on Cohort A was tested on Cohort B and showed moderate to good discrimination ability (Harrell's C: 0.68, 95%-CI: 0.62–0.75). Older age, lower eGFR, and COPD were confirmed as independent predictors for worse survival after EVAR. The updated model showed good discrimination ability (C=0.70, 95%-CI: 0.66–0.75) and was robust in bootstrap validation. The risk score was built using the three variables and split into four risk groups. Patients in the “high risk” groups are expected to have a 5-year survival probability of only 40% (95%-CI: 32–50%), whereas patients in the “low risk” group and have an excellent 5-year survival probability of 89% (95%-CI: 84–95%). Patients in the “low-to-moderate” and “moderate-to-high” risk group have 5-year survival probabilities of 83% (95%-CI: 76–90%) and 68% (95%-CI: 60–79%), respectively.

Conclusion
Age, eGFR and COPD are independent predictors of survival after EVAR. This predictive model could identify low-risk patients with a favourable life expectancy who would likely benefit from EVAR and high-risk patients with a short life expectancy who may not benefit from EVAR at the current diameter threshold.
Long-term outcome of patients treated by TEVAR for type B aortic dissection or intramural hematoma depending on a healthy vs non-healthy proximal landing zone
Authors: Reutersberg B , Meuli L , Menges A , Stoklasa K , Zimmermann A , Düppers P 
Published: June 2022

Abstract

Objective
Thoracic endovascular aortic repair (TEVAR) is the first-line therapy for complicated type B aortic dissection (TBAD) or intramural hematoma (IMH). However, depending on the location of the primary entry tear, there is paucity of data as to whether the proximal landing zone (PLZ) of the stent prosthesis must be in a non-dissected healthy part (healthy landing zone = HLZ) or in the dissected aorta (non-healthy landing zone= non-HLZ).

Methods
Retrospective analysis of patients who underwent TEVAR for acute (&lt;14 days) or subacute (&lt;3 months) TBAD or IMH from 2003–2020 at a single center. A HLZ was defined as a non-dissected aortic segment (length ≥2 cm). Primary endpoints were freedom from aortic reintervention and -growth (≥5 mm). Secondary endpoints involved stroke, retrograde type A aortic dissection, proximal stent graft induced new entry (pSINE), debranching failure, 30-day and overall mortality.

Results
94 patients (age 70 years (interquartile-range (IQR): 59 to 78) were included. 84 (89%) presented with a TBAD and only ten (11%) with an IMH. CTA analysis revealed a HLZ in 62 (66%) patients. Debranching of the left subclavian artery was performed in 21 (22%) patients to extend the PLZ.
The median follow-up time was 20 (IQR: 4.6 to 72.9) months. The overall aortic reintervention rate was 22%. Estimated re-intervention rate at 12 months was 13.1% for HLZ vs. 16.1% for non-HLZ and at 5 years 16.8% for HLZ 29.9% vs. for non-HLZ (P=0.187).
Aortic growth was observed in 12 patients after 2.2 years (IQR: 0.8 to 5.9), with no significant difference in patients with HLZ vs. non-HLZ (11% vs 16%,P=0.535).
No significant differences were observed for the secondary endpoints. 30-day mortality was 10% in both groups, P=1.0. Overall survival was 47% in the HLZ group vs. 41% in the non-HLZ group, P=0.663.
A Cox proportional hazard model for reintervention with mortality as a competing risk showed a trend towards better long-term outcome for patients with a HLZ, hazard ratio 0.451 (95%-CI: 0.186–1.09, P=0.078).

Conclusion
In the majority of patients, it was possible to land in a HLZ. Consistently, reintervention rates, aortic growth, and mortality were higher in patients with non-HLZ compared with HLZ over the mid- and long-term. However, these differences were not statistically significant. Therefore, larger studies are urgently needed.
What Does it Mean to be Contrary to Nature?
Authors: Bradshaw David 
Published: June 2022

AbstractSt. Paul says that same-sex sexual acts are “contrary to nature.” Plainly this is intended as a condemnation, but beyond that its meaning is obscure. In particular, we are given no general account of what it means to be contrary to nature, including what other acts might fit this description. This article attempts to provide such an account. It relies for this purpose on the biblical and classical sources of this idiom as well as its subsequent use within the Greek patristic tradition. It argues that the core meaning of “contrary to nature” is that of violating the integrity of structure and function of the human body. The article further contrasts this biblical and Greek patristic understanding with that of the “sin against nature” developed in the West during the Middle Ages. It argues that they are different in important ways and that a recovery of the biblical and Greek patristic view can help restore the concept of the unnatural to its proper place within Christian ethics.
Emergency computed tomography evaluation of caustic ingestion
Authors: Assalino Michela , Resche-Rigon Matthieu , Corte Helene , Maggiori Leon , Zagdanski Anne Marie , Goere Diane , Sarfati Emile , Cattan Pierre , Chirica Mircea 
Published: June 2022

Summary
Computed tomography (CT) is used increasingly for the emergency assessment of caustic injuries and the need for emergency endoscopy has been challenged. The study evaluates outcomes of caustic ingestion in the modern era and the feasibility of abandoning emergency endoscopy. Between 2013 and 2019, 414 patients (197 men, median age 42 years) were admitted for caustic ingestion. Emergency and long-term outcomes of patients managed by CT and endoscopy (n = 120) and by CT alone (n = 294) were compared. Propensity score-based analysis was performed to limit bias of between-group comparison. A standard mortality ratio (SMR) was used to compare the observed mortality with the expected mortality in the general French population. Complications occurred in 97 (23%) patients and 17 (4.1%) patients died within 90 days of ingestion. Among 359 patients who underwent nonoperative management, 51 (14%) experienced complications and 7 (2%) died. Of 55 patients who underwent emergency surgery, 46 (84%) experienced complications and 10 (18%) died. The SMR was 8.4 for whole cohort, 5.5 after nonoperative management, and 19.3 after emergency surgery. On multivariate analysis, intentional ingestion (P &lt; 0.016), age (P &lt; 0.0001) and the CT grade of esophageal injuries (P &lt; 0.0001) were independent predictors of survival. The CT grade of esophageal injuries was the only independent predictor of success (P &lt; 0.0001). Crude and propensity match analysis showed similar survival in patients managed with and without endoscopy. CT evaluation alone can be safely used for the emergency management of caustic ingestion.
Source parameter estimation of acoustic emissions induced by hydraulic fracturing in the laboratory
Authors: Naoi Makoto , Imakita Keiichi , Chen Youqing , Yamamoto Kazune , Tanaka Rui , Kawakata Hironori , Ishida Tsuyoshi , Fukuyama Eiichi , Arima Yutaro 
Published: June 2022

SUMMARYThe hydraulic fracturing technique is used for resource production, such as in shale gas/oil extraction and enhanced geothermal systems. The effects of fracturing are often monitored via induced earthquakes, and obtaining as much information as possible from those earthquakes is desirable. The stress drop—calculated from the seismic moment Mo and corner frequency fc—is an earthquake-related parameter that can help identify additional characteristics of the seismicity. To investigate the relationship between stress drops and hydraulically induced seismic events, we estimated the Mo and fc of acoustic emission (AE) events during hydraulic fracturing experiments performed in the laboratory in previous studies using 2 Eagle Ford shale and 10 Kurokami-jima granite samples. We estimated Mo by fitting the theoretical spectra to the observed spectra after correcting for the following effects: (1) frequency response of AE transducers under the installation method used in the fracturing experiment, including differences in sensitivity across every transducer used in each experiment; and (2) the difference in radiation pattern coefficients, which depends on the focal mechanisms of each AE event. This analysis used 46 857 focal mechanisms obtained from moment tensor solutions estimated using a deep learning technique. The range of the resultant Mo was found to be 2.8 × 10–5 ≤ Mo ≤ 4.5 × 10–1 [N·m], corresponding to −9.1 ≤ Mw ≤ −6.3, where Mw is the moment magnitude. We also estimated fc using the multiple-empirical Green's function method, reducing the influence of modelling errors in the AE sensor response and transfer function of the medium. Out of the 1053 events whose Mo and fc were estimated, 465 events (44.2 per cent)—regardless of their focal mechanisms—were found to have Mo and fc values consistent with the constant stress drop scaling of shear failure (i.e. shear failures have 0.1–100 MPa stress drops independent of their magnitude) that has been repeatedly confirmed in many previous studies. The remaining events showed lower fc values than those expected from the scaling law. This indicates that high pore pressure in a source region induced by fluid stimulation contributes to the occurrence of low-frequency earthquakes. Overall, we demonstrated that source parameter estimation was possible for laboratory AEs induced by hydraulic fracturing, which can improve our understanding of the characteristics of fluid-induced earthquakes.
The Invasion of the Land in Deep Time: Integrating Paleozoic Records of Paleobiology, Ichnology, Sedimentology, and Geomorphology
Authors: Buatois Luis A , Davies Neil S , Gibling Martin R , Krapovickas Verónica , Labandeira Conrad C , MacNaughton Robert B , Mángano M Gabriela , Minter Nicholas J , Shillito Anthony P 
Published: June 2022

AbstractThe invasion of the land was a complex, protracted process, punctuated by mass extinctions, that involved multiple routes from marine environments. We integrate paleobiology, ichnology, sedimentology, and geomorphology to reconstruct Paleozoic terrestrialization. Cambrian landscapes were dominated by laterally mobile rivers with unstable banks in the absence of significant vegetation. Temporary incursions by arthropods and worm-like organisms into coastal environments apparently did not result in establishment of continental communities. Contemporaneous lacustrine faunas may have been inhibited by limited nutrient delivery and high sediment loads. The Ordovician appearance of early land plants triggered a shift in the primary locus of the global clay mineral factory, increasing the amount of mudrock on the continents. The Silurian–Devonian rise of vascular land plants, including the first forests and extensive root systems, was instrumental in further retaining fine sediment on alluvial plains. These innovations led to increased architectural complexity of braided and meandering rivers. Landscape changes were synchronous with establishment of freshwater and terrestrial arthropod faunas in overbank areas, abandoned fluvial channels, lake margins, ephemeral lakes, and inland deserts. Silurian–Devonian lakes experienced improved nutrient availability, due to increased phosphate weathering and terrestrial humic matter. All these changes favoured frequent invasions to permament establishment of jawless and jawed fishes in freshwater habitats and the subsequent tetrapod colonization of the land. The Carboniferous saw rapid diversification of tetrapods, mostly linked to aquatic reproduction, and land plants, including gymnosperms. Deeper root systems promoted further riverbank stabilization, contributing to the rise of anabranching rivers and braided systems with vegetated islands. New lineages of aquatic insects developed and expanded novel feeding modes, including herbivory. Late Paleozoic soils commonly contain pervasive root and millipede traces. Lacustrine animal communities diversified, accompanied by increased food-web complexity and improved food delivery which may have favored permanent colonization of offshore and deep-water lake environments. These trends continued in the Permian, but progressive aridification favored formation of hypersaline lakes, which were stressful for colonization. The Capitanian and end-Permian extinctions affected lacustrine and fluvial biotas, particularly the invertebrate infauna, although burrowing may have allowed some tetrapods to survive associated global warming and increased aridification.
O01 Nuances of implementing antibiotic stewardship in high-prescribing English general practices: an implementation study
Authors: Tonkin-Crine Sarah , McLeod Monsey , Borek Aleksandra , Campbell Anne , Anyanwu Phillip , Costelloe Ceire , Moore Mike , Hayhoe Benedict , Butler Chris C , Holmes Alison , Sarah Walker A 
Published: June 2022

Abstract

Background
Trials have identified several antimicrobial stewardship (AMS) strategies that effectively reduce antibiotic use in primary care. However, many are not commonly used in England and evidence is lacking around how to support high-prescribing general practices to implement AMS. We co-developed a customizable implementation intervention to improve adoption and use of three AMS strategies; enhanced communication strategies with/without patient leaflets, delayed prescriptions, and point-of-care C-reactive protein testing (POC-CRPT). This study aimed to investigate the use of the implementation intervention in high-prescribing practices and its effect on antibiotic prescribing.

Methods
Nine high-prescribing practices had access to the intervention for 12 months from November 2019. This was primarily delivered remotely via the ‘Antibiotic Optimisation’ website with practices required to identify an in-practice ‘Antibiotic Champion’. In a mixed-methods evaluation, we compared routinely collected prescribing data between 9 intervention and 45 matched control practices using a difference in differences analysis. Intervention material use was assessed through website monitoring and practice requests for supplies. Surveys and interviews were conducted with professionals at baseline and follow-up timepoints to capture experiences of using the intervention.

Results
There was no evidence that the intervention affected antibiotic prescribing. Engagement with intervention materials differed substantially between practices and depended on the individual Antibiotic Champion's preconceptions regarding the AMS strategies and opportunity to do the implementation tasks. Champions in five practices initiated changes to encourage use of at least one of the three AMS strategies, mostly POC-CRPT and patient leaflets. One Champion used the website resources to drive discussions about implementation of all three strategies in their practice. Elsewhere, lack of website engagement meant clinicians did not recognize novelty in the communication and delayed prescription content. POC-CRPT was used most often when equipment was allocated to one person in a practice.

Conclusions
AMS strategies are complex interventions and require clinicians to have detailed knowledge on how to adopt them in practice if they are to reduce antibiotic prescribing. Successful adoption may be achieved by allocating one or two persons to use an AMS strategy rather than all clinicians. Although effective in trials, remote, one-sided provision of AMS strategies is unlikely to change prescribing; initial clinician engagement and understanding needs to be monitored to avoid misunderstanding and suboptimal use.
O02 TRAIL, IP-10, CRP host-protein signature score distinguishes between viral and bacterial infection in sepsis patients
Authors: Stas Jeroen , Arias Cesar A , Bachur Richard , Esposito Susanna , Halabi Salim , Kaplan Sheldon K , Klein Adi , Motov Sergey M , Rothman Richard , Ryan Leticia M , Shiber Shachaf , Tenenbaum Tobias , Weissman Alexandra 
Published: June 2022

Abstract

Background
Sepsis is a life-threatening organ dysfunction syndrome caused by the body's response to infection. Timely and appropriate sepsis management, including appropriate treatment of bacterial infection, improves outcomes. MeMed BV (BV), a test for differentiating between bacterial and viral infection, is based on computational integration of the circulating levels of three proteins (TRAIL, IP-10, CRP). Here we evaluate its ability to differentiate bacterial from viral infection in sepsis patients.

Methods
This was a sub-analysis of sepsis patients recruited prospectively in the Apollo study (NCT04690569). Apollo eligibility required the attending physician's clinical suspicion of acute infection and reported fever. Sepsis was defined as two or more SIRS criteria and a suspected bacterial or viral infection classified by expert adjudication. A bacterial or viral classification required at least 2/3 experts to assign the same aetiology label with confidence ≥90% or all 3 assign with confidence ≥70%. BV was measured using a platform generating a bacterial likelihood score (0–100). Based on pre-defined thresholds, scores 0–34 indicated viral (or other non-bacterial) infection, scores 35 to 65 were equivocal and 66–100 indicated bacterial infection (or coinfection). BV performance was assessed against expert panel classifications.

Results
Seventy-nine out of 1016 eligible Apollo patients had missing heart rate and respiration rate data and a further 136 could not be classified by the experts. Out of the remaining 801 patients, 217 adults with median age of 41.8 years (IQR: 29.2–61) and 149 children with median age of 2.4 years (IQR: 1.4–5.4) had two or more SIRS criteria. A total of 119 patients had at least three SIRS criteria and 39.6% (145/366) of the patients were hospitalized with a median duration of 4 days (IQR: 3–6 days). In the sepsis cohort, 91 patients were classified as bacterial and 275 as viral. BV yielded sensitivity and specificity of 98.8% (95% CI: 93.6%–100%) and 89.7% (95% CI: 85.3%–93.2%) and NPV of 99.6% (95% CI: 97%–99.9%), outperforming PCT [cut-off 0.5 ng/mL; sensitivity 52.8% (95% CI: 42%–63.3%); specificity 86.2% (95% CI: 81.5%–90%); NPV 84.6% (95% CI: 81.5%–87.3%)].

Conclusions
BV accurately distinguished bacterial from viral infection in sepsis patients. This new triage tool has the potential to help with timely identification of bacterial infection, enabling prompt treatment.