bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Insights on the Formation and Breaking Mechanism of Convective Cyclonic Cones in the South Adriatic Pit during Winter 2018
Authors: Pirro A. , Mauri E. , Gerin R. , Martellucci R. , Zuppelli P. , Poulain P. M. 
Published: May 2022

Abstract
The deepwater formation in the northern part of the South Adriatic Pit (Mediterranean Sea) is investigated using a unique oceanographic dataset. In situ data collected by a glider along the Bari–Dubrovnik transect captured the mixing and the spreading/restratification phase of the water column in winter 2018. After a period of about 2 weeks from the beginning of the mixing phase, a homogeneous convective area of ∼300-m depth breaks up due to the baroclinic instability process in cyclonic cones made of geostrophically adjusted fluid. The base of these cones is located at the bottom of the mixed layer, and they extend up to the theoretical critical depth Zc. These cones, with a diameter on the order of internal Rossby radius of deformation (∼6 km), populate the ∼110-km-wide convective site, develop beneath it, and have a short lifetime of weeks. Later on, the cones extend deeper and intrusion from deep layers makes their inner core denser and colder. These observed features differ from the long-lived cyclonic eddies sampled in other ocean sites and formed at the periphery of the convective area in a postconvection period. So far, to the best of our knowledge, only theoretical studies, laboratory experiments, and model simulations have been able to predict and describe our observations, and no other in situ information has yet been provided.
Orographic Effects on Landfalling Lake-Effect Systems
Authors: Gowan Thomas M. , Steenburgh W. James , Minder Justin R. 
Published: May 2022

Abstract
Landfalling lake- and sea-effect (hereafter lake-effect) systems often interact with orography, altering the distribution and intensity of precipitation, which frequently falls as snow. In this study, we examine the influence of orography on two modes of lake-effect systems: long-lake-axis-parallel (LLAP) bands and broad-coverage, open-cell convection. Specifically, we generate idealized large-eddy simulations of a LLAP band produced by an oval lake and broad-coverage, open-cell convection produced by an open lake (i.e., without flanking shorelines) with a downstream coastal plain, 500-m peak, and 2000-m ridge. Without terrain, the LLAP band intersects a coastal baroclinic zone over which ascent and hydrometeor mass growth are maximized, with transport and fallout producing an inland precipitation maximum. The 500-m peak does not significantly alter this structure, but slightly enhances precipitation due to orographic ascent, increased hydrometeor mass growth, and reduced subcloud sublimation. In contrast, a 2000-m ridge disrupts the band by blocking the continental flow that flanks the coastlines. This, combined with differential surface heating between the lake and land, leads to low-level flow reversal, shifting the coastal baroclinic zone and precipitation maximum offshore. In contrast, the flow moves over the terrain in open lake, open-cell simulations. Over the 500-m peak, this yields an increase in the frequency of weaker (<1 m s−1) updrafts and weak precipitation enhancement, although stronger updrafts decline. Over the 2000-m ridge, however, buoyancy and convective vigor increase dramatically, contributing to an eightfold increase in precipitation. Overall, these results highlight differences in the influence of orography on two common lake-effect modes.

Significance Statement
Landfalling lake- and sea-effect snowstorms frequently interact with hills, mountains, and upland regions, altering the distribution and intensity of snowfall. Using high-resolution numerical modeling with simplified lake shapes and terrain features, we illustrate how terrain features affect two common types of lake-effect storms and why long-lake-axis-parallel (LLAP) bands can feature high precipitation rates but weaker orographic enhancement than broad-coverage, open-cell convection.
Scroll-like and platy molybdenite-3R from the Ufaley metamorphic block, South Urals: EBSD, XRD, SEM, EPMA and ICP-MS study
Authors: Belogub Elena V. , Shilovskikh Vladimir V. , Rassomakhin Michail A. , Plotinskaya Olga Yu. , Savichev Alexandr N. , Filippova Ksenia A. , Kirichenko Sergey , Spratt John , Seltmann Reimar 
Published: May 2022

AbstractScroll-like crystals of molybdenite, 2–5 mm in size, were found in phengite rock from the outer contact of the granular quartz vein of the Kyshtym quartz deposit. Platy and partly scrolled molybdenite occur in the same phengite rock from the outer contact of the quartz–feldspar pegmatite of the Slyudyanogorsk mica deposit. Both occurrences are located in the Ufaley metamorphic block in the South Urals. Scroll-like molybdenite crystals can associate with platy and partly twisted crystals in the same samples. The chemical composition of molybdenite was studied by inductively coupled plasma mass spectrometry (ICP-MS) and electron probe microanalysis (EPMA). Polytypes of molybdenite were identified with electron back-scattered diffraction (EBSD) and X-ray diffraction (XRD). Both scroll-like and platy molybdenite crystals are only represented by the 3R polytype, are enriched in Re up to 1 wt.% and contain no other significant impurities. Scroll-like molybdenite is twisted mainly around the crystallographic axis X. Twinning with a rotation of 60 degrees around the Z crystallographic axis is fixed in the plane (ab). The most probable origin of scroll molybdenites is the consequent growth of molybdenite around nucleation centres, which are commonly represented by mica crystals. The formation of the 3R polytype is caused by the difference in dimension of the layers enriched and depleted in rhenium.
Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL
Authors: Diorio Caroline , Murray Ryan , Naniong Mark , Barrera Luis , Camblin Adam , Chukinas John , Coholan Lindsey , Edwards Aaron , Fuller Tori , Gonzales Claudia , Grupp Stephan A. , Ladd Alden , Le Melissa , Messana Angelica , Musenge Faith , Newman Haley , Poh Yeh-Chuin , Poulin Henry , Ryan Theresa , Shraim Rawan , Tasian Sarah K. , Vincent Tiffaney , Young Lauren , Zhang Yingying , Ciaramella Giuseppe , Gehrke Jason , Teachey David T. 
Published: May 2022

Abstract
Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using gene editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target editing outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G to T•A point mutations in T cells, with between 90% and 99% efficiency to silence gene expression without creating DSBs, greatly reducing or eliminating undesired editing outcomes following multiplexed editing as compared with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using CBE, we developed 7CAR8, a CD7-directed allogeneic CART created using 4 simultaneous base edits. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation, or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells, with high potential for clinical translation for relapsed and refractory T-ALL.
CAR T-cell therapy in highly aggressive B-cell lymphoma: emerging biological and clinical insights
Authors: Ali Alaa , Goy Andre , Dunleavy Kieron 
Published: May 2022

Abstract
Recently, significant progress has been made in identifying novel therapies, beyond conventional immunochemotherapy strategies, with efficacy in B-cell lymphomas. One such approach involves targeting the CD19 antigen on B cells with autologous-derived chimeric antigen receptor (CAR) cells. This strategy is highly effective in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), as evidenced by recent regulatory approvals. Recent reports suggest that this is an effective strategy for high-grade B-cell lymphoma. The biological underpinnings of these entities and how they overlap with each other and DLBCL continue to be areas of intense investigation. Therefore, as more experience with CAR T-cell approaches is examined, it is interesting to consider how both tumor cell–specific and microenvironmental factors that define these highly aggressive subsets influence susceptibility to this approach.
RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop
Authors: Xiao Chengwu , Zhang Wei , Hua Meimian , Chen Huan , Yang Bin , Wang Ye , Yang Qing 
Published: May 2022

Abstract
Background
RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progression of RCC have not been explored.

Methods
Bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot were conducted to determine the expression of RNF7 in RCC tissues and cell lines. Knockdown and overexpression experiments were performed to examine the effects of RNF7 on cell viability, apoptosis, and glycolysis in vitro and on tumor growth in nude mice in vivo.

Results
The elevated RNF7 expression in tumor tissues of patients with RCC was correlated with poor survival. RNF7 overexpression inhibited apoptosis and promoted glycolysis in vitro and increased tumor growth in vivo by activating the JAK/STAT3 signaling pathway by ubiquitination of SOCS1. Moreover, RNF7 overexpression affected the sensitivity of RCC cells to sunitinib. Finally, STAT3 activation was necessary for transcriptional induction of RNF7.

Conclusion
These results demonstrate that RNF7 inhibited apoptosis, promoted glycolysis, and inhibited sunitinib sensitivity in RCC cells via ubiquitination of SOCS1, thus activating STAT3 signaling. These suggest the potential for targeting the RNF7-SOCS1/JAK/STAT3 pathway for RCC treatment.
Assessment of stormwater discharge contamination and toxicity for a cold-climate urban landscape
Authors: Popick H. , Brinkmann M. , McPhedran Kerry 
Published: May 2022

Abstract
Background
Stormwater is water resulting from precipitation events and snowmelt running off the urban landscape, collecting in storm sewers, and typically being released into receiving water bodies through outfalls with minimal to no treatment. Despite a growing body of evidence observing its deleterious pollution impacts, stormwater management and treatment in cold climates remains limited, partly due to a lack of quality and loading data and modeling parameters. This study examines the quality of stormwater discharging during the summer season in a cold-climate, semi-arid Canadian city (Saskatoon, Saskatchewan).

Results
Seven stormwater outfalls with mixed-land-use urban catchments > 100 km2 were sampled for four summer (June–August 2019) storm events and analyzed for a suite of quality parameters, including total suspended solids (TSS), chemical oxygen demand (COD), dissolved organic carbon (DOC), metals, and targeted polyaromatic hydrocarbons (PAHs). In addition, assessment of stormwater toxicity was done using the two toxicity assays Raphidocelis subcapitata (algae) and Vibrio fischeri (bacteria). Notable single-event, single-outfall contaminant pulses included of arsenic (420 µg/L), cadmium (16.4 µg/L), zinc (924 µg/L), fluorene (4.95 µg/L), benzo[a]pyrene (0.949 µg/L), pyrene (0.934 µg/L), phenanthrene (1.39 µg/L), and anthracene (1.40 µg/L). The IC50 in both R. subcapitata and V. fischeri was observed, if at all, above expected toxicity thresholds for individual contaminant species. Principal component analysis (PCA) showed no clear trends for individual sampling sites or sampling dates. In contrast, parameters were correlated with each other in groups including DOC, COD, TSS, and reduced algal toxicity; and total dissolved solids (TDS), sum of metals, and pH.

Conclusions
In general, stormwater characteristics were similar to those of previous studies, with a bulk of contamination carried by the first volume of runoff, influenced by a combination of rainfall depth, antecedent dry period, land use, and activity within the catchment. Roads, highways, and industrial areas contribute the bulk of estimated contaminant loadings. More intensive sampling strategies are necessary to contextualize stormwater data in the context of contaminant and runoff volume peaks.
Reducing overall herbicide use may reduce risks to humans but increase toxic loads to honeybees, earthworms and birds
Authors: Cech Ramona M. , Jovanovic Suzanne , Kegley Susan , Hertoge Koen , Leisch Friedrich , Zaller Johann G. 
Published: May 2022

Abstract
Background
Pesticide use has been associated with risks for human health and an overall decline in biodiversity. Although herbicides are the most commonly used pesticides worldwide, they have received less attention in this debate. We investigated the extent to which long-term trends in herbicide use in Austria influence potential toxic exposures to non-target organisms and potential risks to humans. We analyzed official sales data of 101 herbicide active ingredients (AIs) approved in Austria between 2010 and 2019 regarding their ecotoxicological properties based on lethal doses (LD50 and LC50) weighed by their persistence in the environment (DT50) for honeybees (Apis mellifera), earthworms (Eisenia fetida), and birds (Serinus serinus). Human health risks were qualitatively assessed based on official hazard statements for the AIs used.

Results
In Austria, herbicide amounts sold decreased significantly by 24% from 1480 to 1123 tonnes between 2010 and 2019. This also led to a considerable decrease in the amounts of AIs classified by H-statements of the EU Pesticides Database: − 71% acute inhalation toxicity, − 58% reproductive toxicity,− 47% specific target organ toxicity. Yet, 36% of herbicides used were still classified as highly hazardous pesticides according to the Pesticide Action Network. Surprisingly, over the same period, toxic loads to honeybees increased by 487% (oral exposure), while lethal toxic loads to earthworms increased by 498%, and to birds by 580%. This can be attributed to a shift toward the use of more acutely toxic and especially more persistent AIs. The most problematic AI for honeybees, earthworms, birds and humans was the highly persistent diquat. The further ranking of the most toxic herbicides varied considerably depending on the organism. It is important to note that this toxic load assessment, like official environmental risk assessments, evaluates the potential risk but not the actual fatalities or real-world exposure.

Conclusions
Our results show a trade-off between herbicide amounts and toxicological hazards to humans and other non-target organisms. These interdependencies need to be considered when implementing pesticide reduction targets to protect public health and biodiversity, such as the EU´s “farm-to-fork” strategy, which aims to reduce the amounts and risks of synthetic pesticides.
Global prediction model for COVID-19 pandemic with the characteristics of the multiple peaks and local fluctuations
Authors: Dai Haoran , Cao Wen , Tong Xiaochong , Yao Yunxing , Peng Feilin , Zhu Jingwen , Tian Yuzhen 
Published: May 2022

Abstract
Background
With the spread of COVID-19, the time-series prediction of COVID-19 has become a research hotspot. Unlike previous epidemics, COVID-19 has a new pattern of long-time series, large fluctuations, and multiple peaks. Traditional dynamical models are limited to curves with short-time series, single peak, smoothness, and symmetry. Secondly, most of these models have unknown parameters, which bring greater ambiguity and uncertainty. There are still major shortcomings in the integration of multiple factors, such as human interventions, environmental factors, and transmission mechanisms.

Methods
A dynamical model with only infected humans and removed humans was established. Then the process of COVID-19 spread was segmented using a local smoother. The change of infection rate at different stages was quantified using the continuous and periodic Logistic growth function to quantitatively describe the comprehensive effects of natural and human factors. Then, a non-linear variable and NO2 concentrations were introduced to qualify the number of people who have been prevented from infection through human interventions.

Results
The experiments and analysis showed the R2 of fitting for the US, UK, India, Brazil, Russia, and Germany was 0.841, 0.977, 0.974, 0.659, 0.992, and 0.753, respectively. The prediction accuracy of the US, UK, India, Brazil, Russia, and Germany in October was 0.331, 0.127, 0.112, 0.376, 0.043, and 0.445, respectively.

Conclusion
The model can not only better describe the effects of human interventions but also better simulate the temporal evolution of COVID-19 with local fluctuations and multiple peaks, which can provide valuable assistant decision-making information.
Development and evaluation of a Japanese prediction model for low anterior resection syndrome after rectal cancer surgery
Authors: Paku Masakatsu , Miyoshi Norikatsu , Fujino Shiki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Uemura Mamoru , Mizushima Tsunekazu , Yamamoto Hirofumi , Doki Yuichiro , Eguchi Hidetoshi 
Published: May 2022

Abstract
Background
Low anterior resection syndrome (LARS) is the most common complication after rectal cancer resection. We aimed to identify LARS' predictive factors and construct and evaluate a predictive model for LARS.

Methods
This retrospective study included patients with rectal cancer more than 1 year after laparoscopic or robotic-assisted surgery. We administered a questionnaire to evaluate the degree of LARS. In addition, we examined clinical characteristics with univariate and multivariate analysis to identify predictive factors for major LARS. Finally, we divided the obtained data into a learning set and a validation set. We constructed a predictive model for major LARS using the learning set and assessed the predictive accuracy of the validation set.

Results
We reviewed 160 patients with rectal cancer and divided them into a learning set (n = 115) and a validation set (n = 45). Univariate and multivariate analyses in the learning set showed that male (odds ratio [OR]: 2.88, 95% confidence interval [95%CI] 1.11–8.09, p = 0.03), age < 75 years (OR: 5.87, 95%CI 1.14–47.25, p = 0.03) and tumors located < 8.5 cm from the AV (OR: 7.20, 95%CI 2.86–19.49, p < 0.01) were significantly related to major LARS. A prediction model based on the patients in the learning set was well-calibrated.

Conclusions
We found that sex, age, and tumor location were independent predictors of major LARS in Japanese patients that underwent rectal cancer surgery. Our predictive model for major LARS could aid medical staff in educating and treating patients with rectal cancer before and after surgery.
Implementing and evaluating online advance care planning training in UK nursing homes during COVID-19: findings from the Necessary Discussions multi-site case study project
Authors: Cousins Emily , Preston Nancy , Doherty Julie , Varey Sandra , Harding Andrew , McCann Adrienne , Harrison Dening Karen , Finucane Anne , Carter Gillian , Mitchell Gary , Brazil Kevin 
Published: May 2022

Abstract
Background
Advance care planning in nursing homes is important to ensure the wishes and preferences of residents are recorded, especially during the COVID-19 pandemic. However, care staff and family members frequently report feeling unprepared for these conversations. More resources are needed to support them with these necessary discussions. This research aimed to develop, implement and evaluate a website intervention for care staff and family members to provide training and information about advance care planning during COVID-19.

Methods
The research was a primarily qualitative case study design, comprising multiple UK nursing home cases. Data collection included semi-structured interviews with care staff and family members which were coded and analysed thematically. A narrative synthesis was produced for each case, culminating in a thematic cross-case analysis of the total findings. Theoretical propositions were refined throughout the research.

Results
Eight nursing homes took part in the study, involving 35 care staff and 19 family members. Findings were reported according to the RE-AIM framework which identified the reach, effectiveness, adoption, implementation and maintenance of the intervention. Themes included: website content that was well received; suggestions for improvement; implementation barriers and facilitators; examples of organisational and personal impact.

Conclusions
Four theoretical propositions relating to advance care planning in nursing homes are presented, relating to: training and information needs, accessibility, context, and encouraging conversations. Implications for practice and training include an awareness of diverse learning styles, re-enforcing the right to be involved in advance care planning and encouraging opportunities for facilitated discussion.

Trial registration
ISRCTN registry (ID 18003630) on 19.05.21.
Is lobectomy superior to sub-lobectomy in non-small cell lung cancer with pleural invasion? A population-based competing risk analysis
Authors: Song Xue , Xie Yangyang , Zhu Yurou , Lou Yafang 
Published: May 2022

Abstract
Background
Pleural invasion (PL) has been regarded as an unfavorable prognostic factor for non-small cell lung cancer (NSCLC). But there was no agreement on the optimal surgical extent in NSCLC patients with PL. We aimed to compare the survival outcomes of lobectomy and sub-lobectomy in these patients.

Method
2717 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the lobectomy and sub-lobectomy groups. The propensity score matching (PSM) and competing risk analysis were implemented. Then the predictive nomogram was constructed and validated.

Results
2230 Patients received lobectomy while the other 487 patients underwent sub-lobectomy. After 1:1 PSM, the cumulative incidence of cancer-specific death (CSD) was lower in the lobectomy group compared with the sub-lobectomy group (1-year: 12% vs. 15%; 3-year: 30% vs. 37%, 5-year: 34% vs. 45%, P = 0.04). According to the subgroup analysis, the patients who underwent lobectomy suffered lower CSD in the N0–1 stage, adenocarcinoma, and PL-2 cohort (p < 0.05). And there was a significant relationship between the sub-lobectomy group and CSD in the multivariate competing risks regression analysis (HR, 1.26; 95%CI, 1.02–1.56; P = 0.034). Furthermore, a competing event nomogram was constructed to assess the 1-, 3-, and 5-year chances of CSD based on the variables from the multivariate analysis. The 1-, 3-, 5-year area under the receiver operating characteristic curve (AUC) values were 0.720, 0.706, and 0.708 in the training cohort, and 0.738, 0.696, 0.680 in the validation cohorts, respectively. And calibration curves demonstrated ideal consistency between the predicted and observed probabilities of CSD.

Conclusion
Lobectomy should be considered the preferred surgery compared to sub-lobectomy for NSCLC patients with PL. The proposed nomograms presented great prediction ability for these patients.