bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions
Authors: Maoz Asaf , Merenstein Carter , Koga Yusuke , Potter Austin , Gower Adam C , Liu Gang , Zhang Sherry , Liu Hanqiao , Stevenson Christopher , Spira Avrum , Reid Mary E , Campbell Joshua D , Mazzilli Sarah A , Lenburg Marc E , Beane Jennifer 
Published: September 2021

ObjectiveThe immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features.MethodsEndobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and PML outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (ie, found in one patient only) and public (ie, found in two or more patients) TCRs was quantified, and the CDR3 sequences were compared with those found in curated databases with known antigen specificities.ResultsWe detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T cell mediated immune activation (p=4e-4) associated with PML outcome. Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3396 (8.6%) found in more than one sample and 1057 (2.7%) found in two or more patients (ie, public); however, when compared with a public database of CDR3 sequences, 4543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among public TCRs (p<0.001).ConclusionsDecreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.
Diversity matters: the other doctor within the Dutch academic healthcare system
Authors: Tweed TTT , Maduro CV , Güneș NH , Poeze M , Busari J O 
Published: September 2021

IntroductionOver the past year, there has been a worldwide increase in the focus on systemic discrimination and inequitable practices within different societies, particularly concerning race and ethnicity. The inherent (experience of) inequity in racism is notonly limited to individuals but also found in different domains of societal structures, including healthcare and academia. In academia and healthcare organisations, junior Black and Minority Ethnic (BAME) doctors and students regularly find themselves caught between the leaky pipeline phenomenon and hierarchically dependent positions in academic healthcare settings. Voicing their experiences after such encounters is neither an option nor a choice they can do without repercussions. The prejudices, stigmas, implicit biases present within these environments result in segregated practices, where BAME doctors become the ‘other’ doctor (otherism), and based on their religion, ethnicity, migrant background or physical features are boxed into a specific group or category.Reflections & recommendationsThe outcome of this exercise (re-) emphasised that more improvement in the Dutch healthcare systems concerning stigmas and biases towards race and ethnicity are needed to promote the inclusion of future BAME doctors and students. A pivotal turn is urgently needed to repair the racial stigmas and biases that have distorted the image of BAME doctors/students, limiting their academic and professional progress. By structurally implementing focused strategies to promote inclusivity, the current gap within healthcare and the participation between non- BAME and BAME-doctors/students can be bridged, inevitably leading to better healthcare services, safer learning environments and a balanced representation of our multicultural societies in healthcare.We argue that increased self-reflection from such critical inquiry will ultimately result in clear and objective understandings of (pre) existent inequitable practices in our societies.
The $$\uptau $$ challenges at FCC-ee
Authors: Dam Mogens 
Published: September 2021

AbstractAt FCC-ee, about $$1.7 \times 10^{11}\,\hbox {Z} \rightarrow \uptau ^+\uptau ^-$$

1.7
×

10
11

Z
→

τ
+

τ
-

events will be produced. This high statistics in the clean $$\hbox {e}^+\hbox {e}^-$$

e
+

e
-

environment opens the possibility of much improved determinations of $$\uptau $$
τ
-lepton properties and, via the measurement of the $$\uptau $$
τ
polarisation, of the neutral-current couplings of electrons and $$\tau $$
τ
s. Improved measurements of $$\uptau $$
τ
-lepton properties—lifetime, leptonic branching fractions, and mass—allow important tests of lepton universality. The experimental challenge is to match as far as possible statistical uncertainties generally at the $$10^{-5}$$

10

-
5

level. This applies in particular to the lifetime measurement, which is derived from the 2.2-mm $$\uptau $$
τ
average flight distance, and for the branching fraction and polarisation measurements, where the cross-channel contamination is of particular concern. These issues raise strict detector requirements, in particular, on the accuracy of the construction and alignment of the vertex detector and of the precise calorimetric separation and measurement of photons and $$\uppi ^0$$

π
0

s in the collimated $$\uptau $$
τ
decay topologies.
Hypermutation, Mismatch Repair Deficiency, and Defining Predictors of Response to Checkpoint Blockade
Authors: Graham Laura S. , Pritchard Colin C. , Schweizer Michael T. 
Published: September 2021

Abstract
Mutational burden is positively correlated with tumor neoantigen load and studies have demonstrated an association between high tumor mutational burden (TMB) and response to checkpoint blockade. On the basis of a phase II study, the anti-PD-1 therapy, pembrolizumab, was given FDA approval for use in any solid tumor with a high TMB (i.e., &gt;10 mutations/megabase) as assessed by the FoundationOne companion diagnostic. This was an important step in expanding a potentially efficacious treatment option to patients who are likely to benefit and have limited other therapies available. Following this approval, there has been debate regarding the wide applicability of this approval and the most appropriate use of TMB as a predictive biomarker, with several studies questioning the predictive utility of TMB in this context. We discuss the scientific rationale and utility of using TMB as a tool to predict response to immunotherapy as well as address this biomarker's limitations.
Growth Arrest Specific-6 and Axl Coordinate Inflammation and Hypertension
Authors: Van Beusecum Justin P. , Barbaro Natalia R. , Smart Charles D. , Patrick David M. , Loperena Roxana , Zhao Shilin , de la Visitacion Nestor , Ao Mingfang , Xiao Liang , Shibao Cyndya A. , Harrison David G. 
Published: September 2021

Rationale:
There is an intimate relationship between the endothelium and monocytes, and activated endothelial cells promote monocyte transformation to macrophages and dendritic cells (DCs). Recently, a subset of human DCs expressing the receptor tyrosine kinase, Axl and the lectin siglec-6 has been described and termed (AS) DCs.

Objective:
We sought to determine if circulating AS DCs are increased in human hypertension and to examine how Axl signaling contributes to this disease.

Methods and Results:
We demonstrated that circulating AS DCs are increased in hypertensive humans compared with normotensive controls. Pulse pressure in humans also correlated with plasma levels of the Axl agonist GAS6 (growth arrest specific 6). Exposure of human endothelial cells to 10% cyclical stretch increased release of the GAS6, promoted Axl signaling and caused AS DC formation; events that were inhibited by blockade of Axl with R428 or by siRNA knockdown of either endothelial GAS6 or Axl. GAS6/Axl signaling in human monocytes potentiated interleukin 1β production through NLRP3 (nucleotide-binding oligomerization domain, leucine rich tepeat and pyrin domain containing protein)/caspase-1 and caused accumulation of immunogenic isoLG (isolevuglandin)-protein adducts. In mice, the Axl inhibitor R428 or global deletion of Axl attenuated hypertension and renal inflammation caused by Ang II (angiotensin II) infusion. Bone marrow transplant studies demonstrated a role of both stromal and immunologic Axl in Ang II–induced hypertension. Lastly, in freshly harvested human endothelial cells, a striking correlation was observed between the degree of endothelial cell activation as reflected by ICAM-1 (intracellular adhesion molecule 1), isoLG-adduct accumulation, and intracellular GAS6 levels.

Conclusions:
We define a previously unrecognized interaction of human endothelial cells and monocytes that promote formation of AS DCs in hypertension and show a critical role of GAS6 and Axl signaling in both immune cells and endothelial cells. This pathway is potentially a novel therapeutic target to reduce inflammation and end organ damage in hypertension.
Guilty Until Proven Innocent? The EU Global Human Rights Sanctions Regime’s Potential Reversal of the Burden of Proof
Authors: Al-Nassar Hanine , Neele Eveline , Nishioka Shingo , Luthra Vedika 
Published: September 2021

Abstract
This article explores the extent to which the European Global Human Rights Sanctions Regime (eughrsr) should be deemed to contain punitive elements, and if such elements do exist, how the principle of presumption of innocence should be applied to the targeted entity. Taking into account the Engel-criteria, literature research and existing national human rights sanctions regimes, we claim that under specific circumstances the Regime could be considered punitive, and argue that in such situations, certain safeguards with regard to the burden of proof require additional attention.
“Our Age”: Frederick the Great, Classical Warfare, and the Uses and Abuses of Military History
Authors: Storring Adam L. 
Published: September 2021

Abstract
Whereas the long-running Military Revolution debate has focused primarily on changes in military technology and the growth of states in early modern Europe, the example of King Frederick ii (“the Great”) of Prussia highlights how changes in the character of war were perceived by contemporaries, and how they used narratives of change for rhetorical purposes. Frederick and his contemporaries saw their own time as more intellectually advanced than any previous age, and this narrative of intellectual progress existed alongside a narrative of states bringing order. Frederick articulated largely consistent ideas about military history, but also used concepts of the superiority of “our age” to extoll the virtues of his own oblique order of battle, and manipulated narratives of technological change to apologise for his own mistakes. Frederick also turned to an idealised classical world – particularly Julius Caesar – to envisage conquests that went beyond the limits of his own day.
Asymmetric Hurricane Boundary Layer Structure during Storm Decay. Part I: Formation of Descending Inflow
Authors: Ahern Kyle , Hart Robert E. , Bourassa Mark A. 
Published: September 2021

Abstract
In this first part of a two-part study, the three-dimensional structure of the inner-core boundary layer (BL) is investigated in a full-physics simulation of Hurricane Irma (2017). The BL structure is highlighted during periods of intensity change, with focus on features and mechanisms associated with storm decay. The azimuthal structure of the BL is shown to be linked to the vertical wind shear and storm motion. The BL inflow becomes more asymmetric under increased shear. As BL inflow asymmetry amplifies, asymmetries in the low-level primary circulation and thermodynamic structure develop. A mechanism is identified to explain the onset of pronounced structural asymmetries in coincidence with external forcing (e.g., through shear) that would amplify BL inflow along limited azimuth. The mechanism assumes enhanced advection of absolute angular momentum along the path of the amplified inflow (e.g., amplified downshear), which results in local spinup of the vortex and development of strong supergradient flow downwind and along the BL top. The associated agradient force results in the outward acceleration of air immediately above the BL inflow, affecting fields including divergence, vertical motion, entropy advection, and inertial stability. In this simulation, descending inflow in coincidence with amplified shear is identified as the conduit through which low-entropy air enters the inner-core BL, thereby hampering convection downwind and resulting in storm decay.
Clinically Significant Bradycardia and Hypotension Following Consumption of Betel Leaf in a Patient Treated for Chronic Atrial Fibrillation
Authors: Bannister Breyanne E. , Parry Daniel R. , Pouliot Jonathon D. 
Published: September 2021

Purpose: A case of new onset bradycardia and hypotension following betel leaf consumption in combination with verapamil and metoprolol in an atrial fibrillation (AF) patient. Summary: A 66-year-old Nigerian woman presented to the emergency department for evaluation of multiple near syncope episodes with underlying AF and slow ventricular response. After initial evaluation, the patient disclosed she had ingested several betel leaves that morning. She was admitted for observation of severe, progressive hypotension and symptomatic bradycardia. Her past medical history included AF, type 2 diabetes, asthma, obesity, hypertension and hypothyroidism. Her home medications consisted of spironolactone, metoprolol succinate, and verapamil ER. Upon admission, her home medications were held. She received IV fluids and atropine .4 mg IV as needed for symptomatic bradycardia. Approximately 18 h following admission, her vital signs stabilized and her labs returned to baseline. She remained stable and was discharged with a recommendation to continue her home medications at prescribed doses with reduced doses of verapamil and metoprolol and to follow-up with her primary care provider. Conclusion: A patient with a history of AF developed significant hypotension and symptomatic bradycardia after betel leaf consumption resulting in an overnight critical care unit admission. The use of betel leaf is not common in the United States; however, practitioners should be cognizant of the use of complementary and alternative medications like betel leaf and incorporate this knowledge in patient evaluation. Patients consuming betel leaf or betel nut should be evaluated for cardiovascular effects as well as laboratory evaluation for organ damage.
Remote mental health clients prefer face-to-face consultations to telehealth during and after the COVID-19 pandemic
Authors: Amos Andrew James , Middleton Jocelyn , Gardiner Fergus W. 
Published: September 2021

Objective: To guide the efficient and effective provision of mental health services to clients in Central West and Far North Queensland, we surveyed preferences for face-to-face or in-person contact. Methods: A clinician-designed survey of contact preferences was offered to 248 clients of mental health services in Far North and Central West Queensland in mid-2020. With the onset of COVID-19, the survey was modified to measure the impact of the pandemic. Results: Just over half of the services’ clients participated in the survey (50.4%), of whom more were female (63.2%). Of the participants, 46.3% in Far North and 8.6% in Central West Queensland identified as Indigenous. Strong resistance to telehealth before the pandemic across groups (76%) was moderated during COVID-19 (42.4%), an effect that appeared likely to continue past the pandemic for Central West clients (34.5%). Far North clients indicated their telehealth reluctance would return after the pandemic (77.6%). Conclusions: Our results suggest that remote Australians strongly prefer in-person mental health care to telehealth. Although the COVID-19 pandemic increased acceptance of telehealth across regions while social distancing continued, there was evidence that Indigenous Australians were more likely to prefer in-person contact after the pandemic.
Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus
Authors: Lee Hae Lim , Bae Si Hyun , Lee Jaejun , Sung Pil Soo , Lee Sung Won , Jang Jeong Won , Lee Jungmin , Choi Jong Young , Han Nam Ik , Yoon Seung Kew 
Published: September 2021

Background and Aims This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. Methods A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. Results The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002–2011 to 12% in 2012–2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III–V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. Conclusion Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.
Success Rates for the Objectives of US State Cancer Control Plans: A First Look
Authors: Williamson Mark R. 
Published: September 2021

Background A well-designed cancer control plan is an important tool for a nation, state, or community to address the burden of cancer. Furthermore, it provides the opportunity to devise and implement measurable objectives. However, there has been little to no assessment of the success rates of such objectives. Methods I compared the success rate of objectives between US states’ current plan and most recent past plan to determine the proportion of success in the United States overall. I also tested possible reasons for low success rates. Results The mean success rate was 20% for stringent successes (only exact matches between plans) and 28% for loose successes (exact and similar matches between plans). The magnitude of change in percentage between the baseline and target for loose objectives significantly predicted success (P = .0347). Higher change resulted in lower success. However, neither the number of objectives nor the level of overlap significantly predicted success rate. Nor was population size, region, or rural–urban status significantly related to success rate. The most successful states had high proportions of objectives that were measurable and a high number of overlapping objectives. Conclusion I found that objective success rates were low for cancer control plans. To improve success rates, I suggest that future cancer control plans ensure each objective has a measurable baseline and realistically attainable target.
Evaluation of a patient self-medication program in allogeneic hematopoietic stem cell transplantation
Authors: Polito Samantha , Ho Lina , Pang Ian , Dara Celina , Viswabandya Auro 
Published: September 2021

Introduction Patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discharged with multiple new medications. At our institution, a new patient Self Medication Program (SMP) was implemented on the allo-HSCT units. An SMP allows patients to practice self-administration of medications in a controlled environment before discharge. We assessed the impact of the SMP on patient medication knowledge, self-efficacy, adherence, and safety. Patient and staff satisfaction with the SMP was also explored. Methods Participants in the SMP group received medication counseling by a pharmacist and self-managed their medications with nursing supervision until discharge. Participants in the pre-SMP group received medication counseling by a pharmacist at discharge. All participants completed a Medication Knowledge and Self-Efficacy Questionnaire before discharge and at follow-up. Safety endpoints were assessed for SMP participants. Results Twenty-six patients in the pre-SMP group and 25 patients in the SMP group completed both questionnaires. Median knowledge scores in the pre-SMP group versus the SMP group were 8.5/10 versus 10/10 at discharge ( p = 0.0023) and 9/10 versus 10/10 at follow-up ( p = 0.047). Median self-efficacy scores were 38/39 in the pre-SMP group versus 39/39 in the SMP group at both discharge and follow-up ( pdischarge = 0.11, pfollow-up = 0.10). The SMP was associated with at least 1 medication event in 7 participants, but no medication incidents. Patient and staff surveys showed a positive perceived value of the SMP. Conclusion Our results demonstrate that the SMP is associated with durable, improved medication knowledge, a trend towards improved self-efficacy, and largely positive perceptions among both staff and patient participants.