bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR-013: The splanchnic mesenchyme during fetal development is the major source of pancreatic cancer associated fibroblasts
Authors: Han Lu , Wu Yongxia , Parrish Melodie , Patel Khushbu , Yu Xuezhong , Ostrowski Michael , Leone Gustavo 
Published: November 2021

Abstract
In pancreatic ductal adenocarcinoma (PDAC), cancer associated fibroblasts (CAFs) play critical and complex roles in the tumor microenvironment. CAFs are also a major cell type in the desmoplastic stroma in PDAC and may account for half of the entire tumor tissue. Multiple subtypes of CAFs have been suggested, but the tissue origin(s) of CAF subtypes are unknown and genetic tools to robustly target them in vivo are lacking. Here we aimed to examine three potential tissue sources of CAFs: the pancreatic epithelium (through epithelium-to-mesenchyme transition), the bone marrow (through circulation), and the pancreatic mesenchyme or tissue resident fibroblasts (TRFs) in the normal pancreas (through proliferation). We utilized a genetically engineered mouse model of PDAC, where Kras and p53 mutations were engineered in the pancreatic epithelium using an Flp-Frt system. To determine whether the pancreatic epithelium gives rise to CAFs, we permanently labeled the pancreatic epithelium with a GFP reporter and traced their cell descendants by GFP expression. Despite robust GFP labeling of the epithelium, GFP expression was rarely identified in CAFs, suggesting little contribution of epithelium to the CAF pool. To determine whether the bone marrow gives rise to CAFs, we transplanted donor bone marrow carrying a ubiquitously expressed GFP reporter allele to GFP-negative recipient mice. We found that only a small proportion of pancreatic CAFs were tagged with GFP, suggesting their bone marrow origin. Lastly, to determine whether pancreatic TRFs give rise to CAFs, we used an inducible CreER-LoxP system to allow for permanent Tomato labeling in TRFs progenitors, the splanchnic mesenchyme, during mid-gestation. Lineage tracing in PDAC showed that the vast majority of CAFs were labeled with Tomato expression, suggesting their splanchnic origin. Furthermore, certain splanchnic gene expression signatures were persistent in subsets of CAFs in both the PDAC mouse model and human patient samples. In summary, we found that bone marrow contributes to a small proportion of CAFs in PDAC, and the pancreatic epithelium contributes even less. Meanwhile, pancreatic TRFs are derived from the splanchnic mesenchyme during fetal development and they expand to contribute to the vast majority of CAFs in PDAC. Moreover, the persistence of splanchnic signature defines subtypes of CAFs. This study provides approaches to robustly target CAFs in vivo and novel insights into CAF heterogeneity in PDAC.
Citation Format: Lu Han, Yongxia Wu, Melodie Parrish, Khushbu Patel, Xuezhong Yu, Michael Ostrowski, Gustavo Leone. The splanchnic mesenchyme during fetal development is the major source of pancreatic cancer associated fibroblasts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PR-013.
Role of Frailty in Identifying Benefit From Transcatheter Versus Surgical Aortic Valve Replacement
Authors: Strom Jordan B. , Xu Jiaman , Orkaby Ariela R. , Shen Changyu , Song Yang , Charest Brian R. , Kim Dae H. , Cohen David J. , Kramer Daniel B. , Spertus John A. , Gerszten Robert E. , Yeh Robert W. 
Published: November 2021

Background:
Frailty is associated with a higher risk for adverse outcomes after aortic valve replacement (AVR) for severe aortic valve stenosis, but whether or not frail patients derive differential benefit from transcatheter (TAVR) versus surgical (SAVR) AVR is uncertain.

Methods:
We linked adults ≥65 years old in the US CoreValve HiR trial (High-Risk) or SURTAVI trial (Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients) to Medicare claims, February 2, 2011, to September 30, 2015. Two frailty measures, a deficit-based and phenotype-based frailty index (FI), were generated. The treatment effect of TAVR versus SAVR was evaluated within FI tertiles for the primary end point of death and nondeath secondary outcomes, using multivariable Cox regression.

Results:

Of 1442 (linkage rate =60.0%) individuals included, 741 (51.4%) individuals received TAVR and 701 (48.6%) received SAVR (mean age 81.8±6.1 years, 44.0% female). Although 1-year death rates in the highest FI tertiles (deficit-based FI 36.7% and phenotype-based FI 33.8%) were 2- to 3-fold higher than the lowest tertiles (deficit-based FI 13.4%; hazard ratio, 3.02 [95% CI, 2.26–4.02],
P
<0.001; phenotype-based FI 17.9%; hazard ratio, 2.05 [95% CI, 1.58–2.67],
P
<0.001), there were no significant differences in the relative or absolute treatment effect of SAVR versus TAVR across FI tertiles for all death, nondeath, and functional outcomes (all interaction
P
>0.05). Results remained consistent across individual trials, frailty definitions, and when considering the nonlinked trial data.

Conclusions:
Two different frailty indices based on Fried and Rockwood definitions identified individuals at higher risk of death and functional impairment but no differential benefit from TAVR versus SAVR.
Best Practices for Education and Training of Resuscitation Teams for In-Hospital Cardiac Arrest
Authors: Anderson Theresa M. , Secrest Kayla , Krein Sarah L. , Schildhouse Richard , Guetterman Timothy C. , Harrod Molly , Trumpower Brad , Kronick Steven L. , Pribble James , Chan Paul S. , Nallamothu Brahmajee K. 
Published: November 2021

Background:
Survival outcomes following in-hospital cardiac arrest vary significantly across hospitals. Research suggests clinician education and training may play a role. We sought to identify best practices related to the education and training of resuscitation teams.

Methods:
We conducted a descriptive qualitative analysis of semistructured interview data obtained from in-depth site visits conducted from 2016 to 2017 at 9 diverse hospitals within the American Heart Association “Get With The Guidelines” registry, selected based on in-hospital cardiac arrest survival performance (5 top-, 1 middle-, 3 low-performing). We assessed coded data related to education and training including systems learning, informal feedback and debrief, and formal learning through advanced cardiopulmonary life support and mock codes. Thematic analysis was used to identify best practices.

Results:
In total, 129 interviews were conducted with a variety of hospital staff including nurses, chaplains, security guards, respiratory therapists, physicians, pharmacists, and administrators, yielding 78 hours and 29 minutes of interview time. Four themes related to training and education were identified: engagement, clear communication, consistency, and responsive leadership. Top-performing hospitals encouraged employee engagement with creative marketing of new programs and prioritizing hands-on learning over passive didactics. Clear communication was accomplished with debriefing, structured institutional review, and continual, frequent education for departments. Consistency was a cornerstone to culture change and was achieved with uniform policies for simulation practice as well as reinforced, routine practice (weekly, monthly, quarterly). Finally, top-performing hospitals had responsive leadership teams across multiple disciplines (nursing, respiratory therapy, pharmacy and medicine), who listened and adapted programs to fit the needs of their staff.

Conclusions:
Among top-performing hospitals excelling in in-hospital cardiac arrest survival, we identified core elements for education and training of resuscitation teams. Developing tools to expand these areas for hospitals may improve in-hospital cardiac arrest outcomes.
Persistent Opioid Use After Cardiac Implantable Electronic Device Procedures
Authors: Markman Timothy M. , Brown Chase R. , Yang Lin , Guandalini Gustavo S. , Hyman Matthew C. , Arkles Jeffrey S. , Santangeli Pasquale , Schaller Robert D. , Supple Gregory E. , Deo Rajat , Nazarian Saman , Dixit Sanjay , Callans David J. , Epstein Andrew E. , Marchlinski Francis E. , Groeneveld Peter W. , Frankel David S. 
Published: November 2021

Background:
Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown.

Methods:
This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by filling an additional opioid prescription >30 days after the CIED procedure.

Results:

Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52;
P
=0.005), preoperative muscle relaxant (odds ratio, 1.52;
P
<0.001) or benzodiazepine (odds ratio, 1.23;
P
=0.001) use, or opioid use in the previous 5 years (OR, 1.76;
P
<0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED procedures (11.1 versus 12.4%;
P
=0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU.

Conclusions:
POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery. Higher initially prescribed oral morphine equivalent doses were associated with developing POU.
Direct Oral Anticoagulant Adherence of Patients With Atrial Fibrillation Transitioned from Warfarin
Authors: Pundi Krishna N. , Perino Alexander C. , Fan Jun , Schmitt Susan , Kothari Mitra , Szummer Karolina , Askari Mariam , Heidenreich Paul A. , Turakhia Mintu P. 
Published: November 2021

Background
Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin‐treated patients with atrial fibrillation switched to DOAC.

Methods and Results

Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non‐switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA
2
DS
2
‐VASc 3.5±1.6); 32 377 switchers and 96 228 non‐switchers. In 8016 switchers with international normalized ratio data to calculate 180‐day TTR before switch, TTR was low (median 0.45; IQR, 0.26–0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62–1.74],
P
<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low‐TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365‐day proportion of days covered ≥0.8 (OR, 0.49; 0.43–0.57,
P
<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non‐switchers with TTR <0.5, long‐term TTR remained low.

Conclusions
In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre‐switch TTRs. However, TTR trajectories remained low in non‐switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence‐oriented interventions may be beneficial.
Elevated Pulse Pressure and Recurrent Hemorrhagic Stroke Risk in Stroke With Cerebral Microbleeds or Intracerebral Hemorrhage
Authors: Park Jong‐Ho , Lee Juneyoung , Kwon Sun U. , Sung Kwon Hyuk , Hwan Lee Min , Kang Dong‐Wha 
Published: November 2021

Background
Which type of recurrent stroke is associated with pulse pressure (PP) remains uncertain in ischemic stroke with cerebral microbleeds or intracerebral hemorrhage.

Methods and Results
The PICASSO (Prevention of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage) database involving 1454 subjects was analyzed. Subjects were stratified into quartiles according to the distribution of mean PP (mm Hg) during follow‐up (mean, 1.9 years): <47 (first quartile), 48 to 53 (second quartile), 54 to 59 (third quartile), and ≥60 mm Hg (fourth quartile). The primary end point was hemorrhagic stroke, and the secondary end points were ischemic stroke, stroke of any type, and major adverse cardiovascular events. Adjusted time‐dependent area under the receiver operating characteristic curve analysis was performed to assess the prediction accuracy of mean PP. The mean frequency of visit for blood pressure checkup was 9.4±5.5 times. The stroke incidence rate per 100 person‐years was 3.14, 2.24, 5.52, and 6.22, respectively in increasing quartile of mean PP, and the rate of major adverse cardiovascular events was 3.82, 2.84, 6.37, and 7.14, respectively. In the presence of mean arterial pressure, hemorrhagic stroke risk was higher in the highest quartile (adjusted hazard ratio, 6.03; 95% CI, 1.04–34.99) versus the lowest quartile, which was evident at higher mean systolic blood pressure. Higher mean PP as a continuous variable was also a predictor of hemorrhagic stroke (1.09, 1.03−1.15). The time‐dependent area under the receiver operating characteristic curve for hemorrhagic stroke was 0.79.

Conclusions
Long‐term elevated PP with higher systolic blood pressure confers a greater risk of subsequent hemorrhagic stroke among stroke patients with cerebral microbleeds or intracerebral hemorrhage.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier, NCT01013532.
Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis
Authors: Lo Jessica W. , Crawford John D. , Desmond David W. , Bae Hee-Joon , Lim Jae-Sung , Godefroy Olivier , Roussel Martine , Kang Yeonwook , Jahng Seungmin , Köhler Sebastian , Staals Julie , Verhey Frans , Chen Christopher , Xu Xin , Chong Eddie J. , Kandiah Nagaendran , Yatawara Chathuri , Bordet Régis , Dondaine Thibaut , Mendyk Anne-Marie , Brodaty Henry , Traykov Latchezar , Mehrabian Shima , Petrova Neli , Kim Ki Woong , Bae Jong Bin , Han Ji Won , Lipnicki Darren M. , Lam Ben , Sachdev Perminder S. ,   on behalf of the Stroke and Cognition (STROKOG) Collaboration
Published: November 2021

Background:
Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium.

Methods:
Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects.

Results:

A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033];
P
<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=−0.078 SD/year [95% CI, −0.11 to −0.045];
P
<0.001 for global cognition in a subgroup analysis).

Conclusions:
Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.
Interannual Variation in Moisture Sources for the First Rainy Season in South China Estimated by the FLEXPART Model
Authors: Peng Dongdong , Zhou Tianjun , Sun Yong , Lin Ailan 
Published: November 2021

Abstract
The first rainy season (April–June) of South China includes the phases before and after the onset of the South China Sea summer monsoon (SCSSM). Abundant moisture supply is the key dynamic process for precipitation formation. Thus, we employ the FLEXPART model to explore the corresponding moisture sources for the two phases. Before the onset of SCSSM, land regions contribute more moisture to the precipitation over South China than the ocean sources. The main source regions are Southeast Asia (27.01%), the South China Sea (25.96%), South China (11.12%), and the southern part of the northwestern Pacific (10.23%). Land sources (66.87%) play a more important role than ocean sources (33.13%) in the interannual variations, with the contributions mainly from Southeast Asia (47.56%) and the South China Sea (28.79%). After the onset of SCSSM, the climatological contribution of ocean sources is larger than that of land regions, and the main source regions are the South China Sea (20.78%), Southeast Asia (17.51%), the Bay of Bengal (13.76%), and South China (11.21%). For the interannual variations, the contributions of land sources and ocean regions are comparable, and mainly from Southeast Asia (33.53%) and the Bay of Bengal (32.26%). The moisture transports for the interannual variations in first rainy season precipitation over South China before and after the onset of SCSSM are significantly correlated with the east–west contrast of sea surface temperature anomalies over northern part of North Pacific and the uniform warming over Indian Ocean, respectively. This study provides important guidance in improving the regional precipitation predictions and understanding the water resources changes.
The Boreal Summer Zonal Wavenumber-3 Trend Pattern and Its Connection with Surface Enhanced Warming
Authors: Liu Yusen , Sun Cheng , Li Jianping 
Published: November 2021

Abstract
The Northern Hemisphere warms faster under global warming and suffers from more frequent heatwaves, causing considerable social and economic damage. The Northern Hemisphere surface warming exhibits strong regionality, with multiple “hotspots” (areas of enhanced warming), but the relations among them remain unclear. This study finds a dominating zonal wavenumber-3 (ZW3) trend pattern in the upper-level geopotential heights during the boreal summer. The summer geopotential heights show significant increasing trends along the latitudinal circle around 60°N, with three centers located over northeastern America, western Eurasia, and eastern Siberia. The regionally enhanced surface warming trends are closely linked to the increased geopotential through the reduced cloud cover, exhibiting a consistent ZW3 pattern. The model simulations forced by sea surface temperature (SST) and Arctic sea ice cover (SIC) indicate that the SST forcing plays an important role in generating the ZW3 pattern, while the contribution of the SIC is minimal. A theoretical barotropic model can fairly well reproduce the observed ZW3 structure forced by a heating source located over the subtropical North Atlantic, where the SSTs show prominent warming trends and a close relationship with the ZW3 pattern. Our results indicate that the hotspots may be interconnected and are related to a Rossby wave train with a ZW3 structure. It highlights a vital role of tropical/subtropical SSTs on the atmospheric circulation and the associated surface enhanced warming over the mid- to high latitudes, which may have great implications for the coordinated heatwave events and tropical–extratropical teleconnections.
Appendectomy for Vague Symptoms and Equivocal Physical Findings on Physical Exam and Computed Tomography
Authors: Flatley Meaghan , Sokol Kyle K. , Balent Eric M. , Placek Sara B. , Ritenour Joshua S. , Sparkman Brian K. 
Published: November 2021

Background: Appendicitis is a common condition affecting 7-8% of the general population. With the improvement of noninvasive imaging, the diagnostic approach and treatment algorithm for patients with clear signs and symptoms suggestive of acute appendicitis are well agreed-upon. However, patients without pathognomonic signs and symptoms, but with equivocal imaging pose a diagnostic dilemma. These patients may still have acute appendicitis and could potentially benefit from laparoscopic appendectomy. This may be especially true in the subset of patients with appendicoliths. Methods: Our case series exams a group of patients with atypical symptoms who eventually underwent appendectomy and were followed after surgery for at least a month. This case series consists of eight patients with abdominal pain accompanied by a variety of other signs and symptoms in addition to laboratory results and imagining characteristics which were nondiagnostic. These patients had initial Alvarado scores ranging from 0-6. Results: All of these patients were subsequently taken to the operating room for diagnostic laparoscopy and laparoscopic appendectomy. Of these patients, six were known to have appendicoliths based on computed tomography obtained during initial diagnostic workup. Conclusions: All patients underwent a diagnostic laparoscopy and appendectomy. Four had appendicitis and four also had resolution of their symptoms. There exist atypical presentations of appendiceal disease. Patients with abdominal pain/tenderness, even without diagnostic laboratory results or imaging characteristics, may benefit from laparoscopic appendectomy.