bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolving Role of External Forcing in North Atlantic SST Variability over the Last Millennium
Authors: Klavans Jeremy M. , Clement Amy C. , Cane Mark A. , Murphy Lisa N. 
Published: January 2022

AbstractAtlantic multidecadal variability (AMV) impacts temperature, precipitation, and extreme events on both sides of the Atlantic Ocean basin. Previous studies with climate models have suggested that when external radiative forcing is held constant, the large-scale ocean and atmosphere circulation are associated with sea surface temperature (SST) anomalies that have similar characteristics to the observed AMV. However, there is an active debate as to whether these internal fluctuations driven by coupled atmosphere–ocean variability remain influential to the AMV on multidecadal time scales in our modern, anthropogenically forced climate. Here we provide evidence from multiple large ensembles of climate models, paleoreconstructions, and instrumental observations of a growing role for external forcing in the AMV. Prior to 1850, external forcing, primarily from volcanoes, explains about one-third of AMV variance. Between 1850 and 1950, there is a transitional period, where external forcing explains one-half of AMV variance, but volcanic forcing only accounts for about 10% of that. After 1950, external forcing explains three-quarters of AMV variance. That is, the role for external forcing in the AMV grows as the variations in external forcing grow, even if the forcing is from different sources. When forcing is relatively stable, as in earlier modeling studies, a higher percentage of AMV variations are internally generated.
Divergence and Dispersion of Global Eddy Propagation from Satellite Altimetry
Authors: Chen Ge , Chen Xiaoyan , Cao Chuanchuan 
Published: January 2022

Abstract
It is well understood that isolated eddies are presumed to propagate westward intrinsically at the speed of the annual baroclinic Rossby wave. This classic description, however, is known to be frequently violated in both propagation speed and its direction in the real ocean. Here, we present a systematic analysis on the divergence of eddy propagation direction (i.e., global pattern of departure from due west) and dispersion of eddy propagation speed (i.e., zonal pattern of departure from Rossby wave phase speed). Our main findings include the following: 1) A global climatological phase map (the first of its kind to our knowledge) indicating localized direction of most likely eddy propagation has been derived from 28 years (1993–2020) of satellite altimetry, leading to a leaf-like full-angle pattern in its overall divergence. 2) A meridional deflection map of eddy motion is created with prominent equatorward/poleward deflecting zones identified, revealing that it is more geographically correlated rather than polarity determined as previously thought (i.e., poleward for cyclonic eddies and equatorward for anticyclonic ones). 3) The eddy–Rossby wave relationship has a duality nature (waves riding by eddies) in five subtropical bands centered around 27°N and 26°S in the two hemispheres, outside which their relationship has a dispersive nature with dominant waves (eddies) propagating faster in the tropical (extratropical) oceans. Current, wind, and topographic effects are major external forcings responsible for the observed divergence and dispersion of eddy propagations. These results are expected to make a significant contribution to eddy trajectory prediction using physically based and/or data-driven models.
Why Does Convection Weaken over Sumatra Island in an Active Phase of the MJO?
Authors: Zhao Ning , Wu Peiming , Yokoi Satoru , Hattori Miki 
Published: January 2022

Abstract
This study investigated the diurnal cycle of convection over Sumatra Island in an active phase of the Madden–Julian oscillation (MJO) during the Pre-Years of the Maritime Continent (YMC) observation campaign in December 2015 based on in situ and satellite observations and a convection-permitting numerical model. Observations suggest that before the active phase of the MJO in early December, convection occurred frequently over the island during the afternoon and at midnight. By contrast, during the active phase of the MJO in mid-December, afternoon convection over the island was delayed and suppressed, and midnight convection was suppressed. Numerical experiments also successfully replicated the main features of the observed modulations. In general, during the active phase of the MJO, the troposphere became drier in the Sumatra region. While the clouds reduced the solar radiation over the land, the sea breeze was also found to be delayed and weakened. As a result, the afternoon convection initiation was delayed and weakened. Further analyses suggested that the sea breeze was weakened mainly due to the orographic stagnation effect rather than the slightly reduced land–sea temperature contrast. On the other hand, the increased stratiform-anvil clouds induced the anomalous evaporative cooling in the midtroposphere and generated island-scale subsidence during the nighttime, which finally led to the suppression of inland convection. Overall, our study reveals the modulation of diurnal convection over Sumatra Island by an active phase of the MJO and also shows the potential role of land–sea interaction in convection initiation and maintenance.
Single-cell analysis reveals selection of TP53-mutated clones after MDM2 inhibition
Authors: Maslah Nabih , Verger Emmanuelle , Giraudier Stéphane , Chea Mathias , Hoffman Ronald , Mascarenhas John , Cassinat Bruno , Kiladjian Jean-Jacques 
Published: January 2022

Abstract
The mechanisms of transformation of chronic myeloproliferative neoplasms (MPN) to leukemia are largely unknown, but TP53 mutations acquisition is considered a key event in this process. p53 is a main tumor suppressor, but mutations in this protein per se do not confer a proliferative advantage to the cells, and a selection process is needed for the expansion of mutant clones. MDM2 inhibitors may rescue normal p53 from degradation and have been evaluated in a variety of cancers with promising results. However, the impact of these drugs on TP53-mutated cells is underexplored. We report herein evidence of a direct effect of MDM2 inhibition on the selection of MPN patients’ cells harboring TP53 mutations. To decipher whether these mutations can arise in a specific molecular context, we used a DNA single-cell approach to determine the clonal architecture of TP53-mutated cells. We observed that TP53 mutations are late events in MPN, mainly occurring in the driver clone, whereas clonal evolution frequently consists of sequential branching instead of linear consecutive acquisition of mutations in the same clone. At the single-cell level, the presence of additional mutations does not influence the selection of TP53 mutant cells by MDM2 inhibitor treatment. Also, we describe an in vitro test allowing to predict the emergence of TP53 mutated clones. Altogether, this is the first demonstration that a drug treatment can directly favor the emergence of TP53-mutated subclones in MPN.
ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data
Authors: Mann Ludwig , Seibt Kathrin M. , Weber Beatrice , Heitkam Tony 
Published: January 2022

Abstract
Background
Extrachromosomal circular DNAs (eccDNAs) are ring-like DNA structures physically separated from the chromosomes with 100 bp to several megabasepairs in size. Apart from carrying tandemly repeated DNA, eccDNAs may also harbor extra copies of genes or recently activated transposable elements. As eccDNAs occur in all eukaryotes investigated so far and likely play roles in stress, cancer, and aging, they have been prime targets in recent research—with their investigation limited by the scarcity of computational tools.

Results
Here, we present the ECCsplorer, a bioinformatics pipeline to detect eccDNAs in any kind of organism or tissue using next-generation sequencing techniques. Following Illumina-sequencing of amplified circular DNA (circSeq), the ECCsplorer enables an easy and automated discovery of eccDNA candidates. The data analysis encompasses two major procedures: first, read mapping to the reference genome allows the detection of informative read distributions including high coverage, discordant mapping, and split reads. Second, reference-free comparison of read clusters from amplified eccDNA against control sample data reveals specifically enriched DNA circles. Both software parts can be run separately or jointly, depending on the individual aim or data availability. To illustrate the wide applicability of our approach, we analyzed semi-artificial and published circSeq data from the model organisms Homo sapiens and Arabidopsis thaliana, and generated circSeq reads from the non-model crop plant Beta vulgaris. We clearly identified eccDNA candidates from all datasets, with and without reference genomes. The ECCsplorer pipeline specifically detected mitochondrial mini-circles and retrotransposon activation, showcasing the ECCsplorer’s sensitivity and specificity.

Conclusion
The ECCsplorer (available online at https://github.com/crimBubble/ECCsplorer) is a bioinformatics pipeline to detect eccDNAs in any kind of organism or tissue using next-generation sequencing data. The derived eccDNA targets are valuable for a wide range of downstream investigations—from analysis of cancer-related eccDNAs over organelle genomics to identification of active transposable elements.
General practitioners’ experiences with, views of, and attitudes towards, general practice-based pharmacists: a cross-sectional survey
Authors: Hasan Ibrahim Ameerah S. , Barry Heather E. , Hughes Carmel M. 
Published: January 2022

Abstract
Background
There is limited United Kingdom (UK) literature on general practice-based pharmacists’ (PBPs’) role evolution and few studies have explored general practitioners’ (GPs’) experiences on pharmacist integration into general practice. Therefore, this study aimed to investigate GPs’ experiences with, views of, and attitudes towards PBPs in Northern Ireland (NI).

Methods
A paper-based self-administered questionnaire comprising four sections was mailed in 2019 to 329 general practices across NI and was completed by one GP in every practice who had most contact with the PBP. Descriptive analyses were used and responses to open-ended questions were analysed thematically.

Results
The response rate was 61.7% (203/329). There was at least one PBP per general practice. All GPs had face-to-face meetings with PBPs, with three-quarters (78.7%, n = 159) meeting with the PBP more than once a week. Approximately two-thirds of GPs (62.4%, n = 126) reported that PBPs were qualified as independent prescribers, and 76.2% of these (n = 96/126) indicated that prescribers were currently prescribing for patients. The majority of GPs reported that PBPs always/very often had the required clinical skills (83.6%, n = 162) and knowledge (87.0%, n = 167) to provide safe and effective care for patients. However, 31.1% (n = 61) stated that PBPs only sometimes had the confidence to make clinical decisions. The majority of GPs (> 85%) displayed largely positive attitudes towards collaboration with PBPs. Most GPs agreed/strongly agreed that PBPs will have a positive impact on patient outcomes (95.0%, n = 192) and can provide a better link between general practices and community pharmacists (96.1%, n = 194). However, 24.8% of GPs (n = 50) were unclear if the PBP role moved community pharmacists to the periphery of the primary care team. An evaluation of the free-text comments indicated that GPs were in favour of more PBP sessions and full-time posts.

Conclusion
Most GPs had positive views of, and attitudes towards, PBPs. The findings may have implications for future developments in order to extend integration of PBPs within general practice, including the enhancement of training in clinical skills and decision-making. Exploring PBPs’, community pharmacists’ and patients’ views of this role in general practice is required to corroborate study findings.
Physical examination performed by general practitioners in 5 community health service institutions in Beijing: an observational study
Authors: Wei Yun , Wang Feiyue , Pan Zhaolu , Wang Meirong , Jin Guanghui , Lu Xiaoqin 
Published: January 2022

Abstract
Background
Physical examination is a core component of consultation. Little is known about the status quo of physical examinations performed by general practitioners in community health service institutions in China. The aim of this study was to investigate general practitioners’ performance of physical examinations in consultations.

Methods
An observational study was conducted in 5 community health service institutions in Beijing between November 2019 and January 2020. Eleven general practitioners were observed for one workday. Information of consecutive consultations was recorded including patient characteristics, reasons for encounter, physical examinations performed by general practitioners, length of consultation time and time spent on specific activities in consultations.

Results
A total of 682 consultations of 11 general practitioners were recorded. Physical examinations were performed in 126 consultations (15.8%). Physical examination was more likely to be performed in patients visiting with symptoms (P < 0.001). Majority of the 126 physical examinations were distributed in “Head, face, and neck examination” (n = 54, 42.9%) and “Cardiovascular examination” (n = 55, 43.7%). No physical examination was performed on skin, male genitalia, female breasts and genitalia, and neurological systems. Total 2823 min of activities were observed and recorded. General practitioners only spent 3.1% of the recorded time on physical examination, which was less than the time spent on taking history (18.2%), test (4.9%), diagnosis (22.7%), therapy (38.4%), and health education (8.6%). The average time spent on physical examinations was 0.8±0.4 min per consultation.

Conclusion
Physical examination was insufficiently performed by general practitioners in community health service institutions in Beijing. More time and commitment should be advocated for improving the quality of physical examinations in primary care.
Attitudes & behaviors toward the management of tobacco smoking patients: qualitative study with French primary care physicians
Authors: Coindard Guillaume , Acquadro Michaël , Chaumont Raphaël , Arnould Benoit , Boisnault Philippe , Collignon-Portes Rachel , Duhot Didier , Raineri François , Tugaut Béatrice , Aubin Henri-Jean 
Published: January 2022

AbstractBackgroundSmoking cessation is a major public health issue. In France, primary care physicians (PCP) are the first contact points for tobacco management. The objective of this study was to understand how PCPs are involved in the management of smoking cessation: ownership, commitment, barriers.MethodsA qualitative study was conducted using group and individual semi-structured techniques with PCPs. A thematic analysis of verbatim transcripts was performed to identify concepts and sub-concepts of interest. Saturation was evaluated retrospectively to ensure adequate sample size.ResultsA sample of 35 PCPs were interviewed, 31 in four focus groups and four in individual interviews. PCPs discussed their roles in the management of tobacco smoking cessation, including the different strategies they are using (e.g., Minimal Intervention Strategy, Motivational Interviewing), the multiple barriers encountered (e.g., lack of time, patients’ resistance to medical advice), the support resources and the treatment and intervention they prescribed (e.g. nicotine replacement therapy, supporting therapist).ConclusionsThis study provides a better understanding of the beliefs, attitudes, and behaviors of PCPs in managing smoking cessation. Guiding and encouraging patients toward smoking cessation remains a major objective of PCPs. While PCPs reported that progress has been made in recent years in terms of tools, technology and general awareness, they still face major barriers, some of which could be overcome by appropriate training.
Inflammation-scores as prognostic markers of overall survival in lung cancer: a register-based study of 6,210 Danish lung cancer patients
Authors: Winther-Larsen Anne , Aggerholm-Pedersen Ninna , Sandfeld-Paulsen Birgitte 
Published: January 2022

Abstract
Background
Inflammation-scores based on general inflammation markers are suggested as prognostic markers of overall survival (OS) in lung cancer. However, whether these inflammation-scores improves the prognostication performed by well-established prognostic markers is unsettled. In a large register-based lung cancer patient cohort, nine different inflammation-scores were compared, and their ability to optimize the prognostication of OS was evaluated.

Methods
Lung cancer patients diagnosed from 2009–2018 in The Central Denmark Region were identified in the Danish Lung Cancer Registry. Pre-treatment inflammation markers were extracted from the clinical laboratory information system. Prognostication of OS was evaluated by Cox proportional hazard models. Comparison of the inflammation-scores and their added value to established prognostic markers were assessed by Akaike's information criteria and Harrel's C-index.

Results
In total, 5,320 patients with non-small cell lung cancer (NSCLC) and 890 patients with small cell lung cancer (SCLC) were identified. In NSCLC, the Aarhus composite biomarker score (ACBS), including albumin, C-reactive protein, neutrophil count, lymphocyte count and haemoglobin, and the neutrophil-lymphocyte-ratio (NLR) were superior. Furthermore, they improved the prognostication of OS significantly (p <0.0001) (ACBS: HR: 2.24 (95%CI: 1.97–2.54); NLR: HR: 1.58 (95%CI: 1.47 – 1.69)). In SCLC, three scores were equally superior and improved the prognostication of OS p < 0.0001): neutrophil–lymphocyte-ratio (HR:1.62 (95%CI: 1.38–1.90)), modified Glasgow Prognostic Score (mGPS) (HR:1.70 (95%CI: 1.55–1.86) and the Combined NLR and GPS (CNG) (HR:2.10 (95%CI: 1.77–2.49).

Conclusions
The ACBS was the optimal score in NSCLC, whereas neutrophil–lymphocyte-ratio, mGPS and CNG were equally superior in SCLC. Additionally, these inflammation-scores all optimised the prognostication of OS and added value to well-established prognostic markers.
An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer
Authors: Bennedsen Astrid Louise Bjørn , Cai Luyi , Hasselager Rune Petring , Özcan Aysun Avci , Mohamed Khadra Bashir , Eriksen Jens Ole , Eiholm Susanne , Bzorek Michael , Fiehn Anne-Marie Kanstrup , Hviid Thomas Vauvert F. , Gögenur Ismail 
Published: January 2022

Abstract
Background
The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells’ ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer.

Methods
We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated.

Results
We included 188 patients undergoing colon cancer resections in 2011–2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64–6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06–0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68–157.32] and HR = 7.56, 95%CI [1.06–54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS.

Conclusions
In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.
“You can’t un-ring the bell”: a mixed methods approach to understanding veteran and family perspectives of recovery from military-related posttraumatic stress disorder
Authors: St. Cyr Kate , Liu Jenny J. W. , Cramm Heidi , Nazarov Anthony , Hunt Renee , Forchuk Callista , Deda Erisa , Richardson J. Don 
Published: January 2022

Abstract
Background
Military-related posttraumatic stress disorder (PTSD) is a complex diagnosis with non-linear trajectories of coping and recovery. Current approaches to the evaluation of PTSD and treatment discontinuation often rely on biomedical models that dichotomize recovery based on symptom thresholds. This approach may not sufficiently capture the complex lived experiences of Veterans and their families. To explore conceptualizations of recovery, we sought perspectives from Veterans and their partners in a pilot study to understand: 1) how Veterans nearing completion of treatment for military-related PTSD and their partners view recovery; and 2) the experience of progressing through treatment towards recovery.

Methods
We employed a concurrent mixed methods design. Nine Veterans nearing the end of their treatment at a specialized outpatient mental health clinic completed quantitative self-report tools assessing PTSD and depressive symptom severity, and an individual, semi-structured interview assessing views on their treatment and recovery processes. Veterans’ partners participated in a separate interview to capture views of their partners’ treatment and recovery processes. Descriptive analyses of self-report symptom severity data were interpreted alongside emergent themes arising from inductive content analysis of qualitative interviews.

Results
While over half of Veterans were considered “recovered” based on quantitative assessments of symptoms, individual reflections of “recovery” were not always aligned with these quantitative assessments. A persistent narrative highlighted by participants was that recovery from military-related PTSD was not viewed as a binary outcome (i.e., recovered vs. not recovered); rather, recovery was seen as a dynamic, non-linear process. Key components of the recovery process identified by participants included a positive therapeutic relationship, social support networks, and a toolkit of adaptive strategies to address PTSD symptoms.

Conclusions
For participants in our study, recovery was seen as the ability to navigate ongoing issues of symptom management, re-engagement with meaningful roles and social networks, and a readiness for discontinuing intensive, specialized mental health treatment. The findings of this study highlight important considerations in balancing the practical utility of symptom severity assessments with a better understanding of the treatment discontinuation-related needs of Veterans with military-related PTSD and their families, which align with a contemporary biopsychosocial approach to recovery.