bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II clinical and immune correlate study of adjuvant nivolumab plus ipilimumab for high-risk resected melanoma
Authors: Khushalani Nikhil I , Vassallo Melinda , Goldberg Judith D , Eroglu Zeynep , Kim Younchul , Cao Biwei , Ferguson Robert , Monson Kelsey R , Kirchhoff Tomas , Amato Carol M , Burke Paulo , Strange Ann , Monk Emily , Gibney Geoffrey Thomas , Kudchadkar Ragini , Markowitz Joseph , Brohl Andrew S , Pavlick Anna , Richards Alison , Woods David M , Weber Jeffrey 
Published: November 2022

BackgroundAdjuvant therapy for high-risk resected melanoma with programmed cell-death 1 blockade results in a median relapse-free survival (RFS) of 5 years. The addition of low dose ipilimumab (IPI) to a regimen of adjuvant nivolumab (NIVO) in CheckMate-915 did not result in increased RFS. A pilot phase II adjuvant study of either standard dose or low dose IPI with NIVO was conducted at two centers to evaluate RFS with correlative biomarker studies.MethodsPatients with resected stages IIIB/IIIC/IV melanoma received either IPI 3 mg/kg and NIVO 1 mg/kg (cohort 4) or IPI 1 mg/kg and NIVO 3 mg/kg (cohorts 5 and 6) induction therapy every 3 weeks for 12 weeks, followed by maintenance NIVO. In an amalgamated subset of patients across cohorts, peripheral T cells at baseline and on-treatment were assessed by flow cytometry and RNA sequencing for exploratory biomarkers.ResultsHigh rates of grade 3–4 adverse events precluded completion of induction therapy in 50%, 35% and 7% of the patients in cohorts 4, 5 and 6, respectively. At a median of 63.9 months of follow-up, 16/56 patients (29%) relapsed. For all patients, at 5 years, RFS was 71% (95% CI: 60 to 84), and overall survival was 94% (95% CI: 88 to 100). Expansion of CD3+CD4+CD38+CD127−GARP− T cells, an on-treatment increase in CD39 expression in CD8+ T cells, and T-cell expression of phosphorylated signal-transducer-and-activator-of-transcription (STAT)2 and STAT5 were associated with relapse.ConclusionsAdjuvant IPI/NIVO at the induction doses used resulted in promising relapse-free and overall survival, although with a high rate of grade 3–4 adverse events. Biomarker analyses highlight an association of ectoenzyme-expressing T cells and STAT signaling pathways with relapse, warranting future validation.Trial registration numberNCT01176474andNCT02970981.
Evaluating disease control following belimumab treatment in patients with SLE enrolled in the US OBSErve study
Authors: Hunnicutt Jacob N , Fairburn-Beech Jolyon , Georgiou Mary Elizabeth , Richards Anna , Gregan Yun Irene , Quasny Holly , Chauhan Deven 
Published: November 2022

ObjectiveTo characterise disease control and remission in patients with SLE receiving belimumab for up to 12 months in the real world.MethodsThis post hoc analysis (GSK Study 213502) used data from the US evaluation Of use of Belimumab in clinical practice SEttings (OBSErve) study (GSK Study 117295), an observational cohort study of adults with SLE initiating and continuing belimumab for ≥6 months. Data were collected every 6 months by physician chart review; details of disease activity using the Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) score were collected if routinely used by physicians. Disease control definitions evaluated were SELENA-SLEDAI score of ≤2 at 12 months, SELENA-SLEDAI score of ≤2 and glucocorticoid (prednisone equivalent) dose of ≤5 mg/day at 12 months, SELENA-SLEDAI score of ≤2 and glucocorticoid dose of ≤5 mg/day at both 6 and 12 months. Disease remission definition was SELENA-SLEDAI score=0 at 12 months. Glucocorticoid dose during follow-up was quantified.ResultsUS OBSErve enrolled 501 patients, 90 of whom had eligible SELENA-SLEDAI scores for inclusion in this analysis. Mean (SD) SELENA-SLEDAI scores were 13.1 (3.0) at baseline and 4.9 (3.4) at 12 months. Disease control at 12 months was achieved by 31.1% of patients when defined as a SELENA-SLEDAI score of ≤2 (95% CI 21.8 to 41.7); this decreased to 25.6% when requiring a SELENA-SLEDAI score of ≤2 and glucocorticoid dose of ≤5 mg/day (95% CI 16.9 to 35.8) and 17.8% when requiring a SELENA-SLEDAI score of ≤2 and glucocorticoid dose of ≤5 mg/day at both 6 and 12 months (95% CI 10.5 to 27.3). No patient achieved remission at 12 months. Glucocorticoids decreased from a baseline median of 20.0 mg/day (IQR 15.0–30.0) to 5.0 mg/day (IQR 0–10.0) at 12 months.ConclusionImproved disease control and reduced glucocorticoid use was achieved for a proportion of patients following up to 12 months of belimumab treatment in a US real-world setting.
Three decades of environmental change studies at alpine Finse, Norway: climate trends and responses across ecological scales
Authors: Roos Ruben E. , Asplund Johan , Birkemoe Tone , Halbritter Aud H. , Olsen Siri Lie , Vassvik Linn , van Zuijlen Kristel , Klanderud Kari 
Published: November 2022

The International Tundra Experiment (ITEX) was established to understand how environmental change impacts Arctic and alpine ecosystems. The success of the ITEX network has allowed for several important across-site syntheses, and for some ITEX sites enough data have now been collected to perform within-site syntheses on the effects of environmental change across ecological scales. In this study, we analyze climate data and synthesize three decades of research on the ecological effects of environmental change at the ITEX site at Finse, southern Norway. We found a modest warming rate of +0.36 °C per decade and minor effects on growing season length. Maximum winter snow depth was highest in winters with a positive North Atlantic Oscillation. Our synthesis included 80 ecological studies from Finse, biased towards primary producers with few studies on ecological processes. Species distributions depended on microtopography and microclimate. Experimental warming had contrasting effects on abundance and traits of individual species and only modest effects at the community level above and below ground. In contrast, nutrient addition experiments caused strong responses in primary producer and arthropod communities. This within-site synthesis enabled us to conclude how different environmental changes (experimental and ambient warming, nutrient addition, and environmental gradients) impact across ecological scales, which is challenging to achieve with across-site approaches.
Multiboson signals in the UN2HDM
Authors: Aguilar-Saavedra J. A. , Joaquim F. R. , Seabra J. F. 
Published: November 2022

AbstractWe address multiboson production from a heavy $$Z'$$

Z
′

resonance in the context of the UN2HDM, a standard model extension with an additional $$\text {U}(1)'$$

U

(
1
)

′

symmetry and an enlarged scalar sector with an extra doublet and a singlet. After taking into account theoretical and experimental constraints on the model, it turns out this type of signals – mostly uncovered by current searches – could be sizeable. We focus on three benchmark scenarios, each of them predicting up to 4000 multiboson events with the LHC Run 2 collected luminosity. Anomaly-detection methods could uncover those signals, if present in data.
Parameterisation space for Cornell potential in a QCD potential model
Authors: Pathak Krishna Kingkar , Bhattacharya Satyadeep , Das Tapashi 
Published: November 2022

AbstractWe make a critical analysis on the free parameters of the Cornell potential $$-\frac{4\alpha _{s}}{3r}+br+c$$

-

4

α
s

3
r

+
b
r
+
c

and provide a parameterisation space for the strong coupling constant $$\alpha _{s}$$

α
s

and the constant shift ‘c’ for choosing linear part as perturbation in the potential model. In the analysis of heavy-light mesons $$(D,D_{s},B,B_{s}\ \text {and}\ B_{c})$$

(
D
,

D
s

,
B
,

B
s

and

B
c

)

, we have found a wide range of values for the coupling constant i.e $$0.20 \le \alpha _{s}\le 0.64$$

0.20
≤

α
s

≤
0.64

with $$-1.2 \le c \le -0.66$$

-
1.2
≤
c
≤
-
0.66

which can be used to treat the confining part as perturbation.
Neural Photo-Finishing
Authors: Tseng Ethan , Zhang Yuxuan , Jebe Lars , Zhang Xuaner , Xia Zhihao , Fan Yifei , Heide Felix , Chen Jiawen 
Published: November 2022

Image processing pipelines are ubiquitous and we rely on them either directly, by filtering or adjusting an image post-capture, or indirectly, as image signal processing (ISP) pipelines on broadly deployed camera systems. Used by artists, photographers, system engineers, and for downstream vision tasks, traditional image processing pipelines feature complex algorithmic branches developed over decades. Recently, image-to-image networks have made great strides in image processing, style transfer, and semantic understanding. The differentiable nature of these networks allows them to fit a large corpus of data; however, they do not allow for intuitive, fine-grained controls that photographers find in modern photo-finishing tools.
This work closes that gap and presents an approach to making complex photo-finishing pipelines differentiable, allowing legacy algorithms to be trained akin to neural networks using first-order optimization methods. By concatenating tailored network proxy models of individual processing steps (e.g. white-balance, tone-mapping, color tuning), we can model a non-differentiable reference image finishing pipeline more faithfully than existing proxy image-to-image network models. We validate the method for several diverse applications, including photo and video style transfer, slider regression for commercial camera ISPs, photography-driven neural demosaicking, and adversarial photo-editing.
Topical Application of Chinese Formula Yeliangen Promotes Wound Healing in Streptozotocin-Induced Diabetic Rats
Authors: Al-Romaima Abdulbaset , Guan Xiong , Qin Xihui , Liao Yinan , Qin Guiming , Tang Shixiong , Feng Jie 
Published: November 2022

Diabetic wound is one of the most severe complications of diabetes mellitus (DM). Despite the associated risks of wound healing impairment in diabetes, treatment strategies remain limited. Yeliangen (YLG) is a Chinese formulation mainly composed of the rhizome of Coptis chinensis, the root of Isatis tinctoria, and the leaf of Isatis indigotica. We investigated the wound healing effects of YLG in type 2 diabetic (T2DM) rats, which were induced by intraperitoneal administration of streptozotocin after a high-fat diet for four weeks.

3
×
3

c

m

2

full-thickness excisional wounds were created on the dorsal surface of rats and then divided to control (DC), negative (DPJ), positive (DPC), and YLG-treated (DYLG) groups. Rat’s wounds were treated twice daily for 21 days. Wound area and wound contraction were detected on days 0, 3, 7, 14, and 21. Histopathological examinations were performed by H&E staining and immunohistochemistry (IHC). The biochemical parameters, mRNAs, and protein expressions were analyzed through enzyme-linked immunoassays (ELISA), qPCR, and western blot, respectively. Compared with other groups, the histological changes of wound tissue in the DYLG group were improved, and the expressions of CD31, eNOS, and PCNA were significantly upregulated. Besides, YLG significantly reduced the inflammatory factors’ expressions of TNF-α, NF-κB, MMP-9, and IL-1B on days 7, 14, and 21 postwounding. Moreover, YLG induced angiogenesis and neovascularization by significantly increasing the levels of VEGF, TGF-β1, EGF, PDGF, and SDF-1α on days 3, 7, and 14. In conclusion, YLG improved wound healing by reducing inflammation and increasing angiogenesis which may provide an alternative and effective approach for diabetic wound therapy.
Fermatean Cubic Fuzzy Aggregation Operators and Their Application in Multiattribute Decision-Making Problems
Authors: Riaz Muhammad , Zeb Aurang , Ali Fawad , Naeem Muhammad , Arjika Sama 
Published: November 2022

The purpose of aggregation methods is to convert a list of objects of a set into a single object of the same set usually by an

n

-arry function, so-called aggregation operator. The key features of this work are the aggregation operators, because they are based on a novel set called Fermatean cubic fuzzy set (F-CFS). F-CFS has greater spatial scope and can deal with more ambiguous situations where other fuzzy set extensions fail to support them. For this purpose, the notion of F-CFS is defined. F-CFS is the transformation of intuitionistic cubic fuzzy set (I-CFS), Pythagorean cubic fuzzy set (P-CFS), interval-valued cubic fuzzy set, and basic orthopair fuzzy set and is grounded on the constraint that “the cube of the supremum of membership plus nonmembership degree is

≤
1

”. We have analyzed some properties of Fermatean cubic fuzzy numbers (F-CFNs) as they are the alteration

of basic properties of I-CFS and P-CFS. We also have defined the score and deviation degrees of F-CFNs. Moreover, the distance measuring function between two F-CFNs is defined which shows the space between two F-CFNs. Based on this notion, the aggregation operators namely Fermatean cubic fuzzy-weighted averaging operator (F-CFWA), Fermatean cubic fuzzy-weighted geometric operator (F-CFWG), Fermatean cubic fuzzy-ordered-weighted averaging operator (F-CFOWA), and Fermatean cubic fuzzy-ordered-weighted geometric operator (F-CFOWG) are developed. Furthermore, the notion is applied to multiattribute decision-making (MADM) problem in which we presented our objectives in the form of F-CFNs to show the effectiveness of the newly developed strategy.
Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes
Authors: Prasad Ram , Floyd Jason L. , Dupont Mariana , Harbour Angela , Adu-Agyeiwaah Yvonne , Asare-Bediako Bright , Chakraborty Dibyendu , Kichler Kara , Rohella Aayush , Li Calzi Sergio , Lammendella Regina , Wright Justin , Boulton Michael E. , Oudit Gavin Y. , Raizada Mohan K. , Stevens Bruce R. , Li Qiuhong , Grant Maria B. 
Published: November 2022

Background:
We examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D).

Methods:

T1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II);
Akita
mice were orally administered a
Lactobacillus paracasei
(LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention.
Akita
mice with genetic overexpression of
humanAce2
by small intestine epithelial cells (
Vil-Cre.hAce2KI-Akita
) were similarly examined. After 9 months of T1D, circulatory, enteral, and ocular end points were assessed.

Results:
T1D subjects exhibit elevations in gut-derived circulating immune cells (ILC1 cells) and higher gut leakage markers, which were positively correlated with plasma Ang II and DR severity. The LP-ACE2 prevention cohort and genetic overexpression of intestinal ACE2 preserved barrier integrity, reduced inflammatory response, improved hyperglycemia, and delayed development of DR. Improvements in glucose homeostasis were due to intestinal MasR activation, resulting in a GSK-3β (glycogen synthase kinase-3 beta)/c-Myc (cellular myelocytomatosis oncogene)-mediated decrease in intestinal glucose transporter expression. In the LP-ACE2 intervention cohort, gut barrier integrity was improved and DR reversed, but no improvement in hyperglycemia was observed. These data support that the beneficial effects of LP-ACE2 on DR are due to the action of ACE2, not improved glucose homeostasis.

Conclusions:

Dysregulated systemic and intestinal renin-angiotensin system was associated with worsening gut barrier permeability, gut-derived immune cell activation, systemic inflammation, and progression of DR in human subjects. In
Akita
mice, maintaining intestinal ACE2 expression prevented and reversed DR, emphasizing the multifaceted role of the intestinal renin-angiotensin system in diabetes and DR.
Detrimental Role of PDZ-RhoGEF in Pathological Cardiac Hypertrophy
Authors: Huang Jia , Qu Qingrong , Dai Yuxiang , Ren Daoyuan , Qian Juying , Ge Junbo 
Published: November 2022

Background:
Postsynaptic density 95/disk-large/ZO-1 Rho guanine nucleotide exchange factor (PDZ-RhoGEF, PRG) functions as a RhoGEF for activated Gα13 and transmits activation signals to downstream signaling pathways in various pathological processes. Although the prohypertrophic effect of activated Gα13 (guanine nucleotide binding protein alpha 13; a heterotrimeric G protein) is well-established, the role of PDZ-RhoGEF in pathological cardiac hypertrophy is still obscure.

Methods:
Genetically engineered mice and neonatal rat ventricular myocytes were generated to investigate the function of PRG in pathological myocardial hypertrophy. The prohypertrophic stimuli-induced alternations in the morphology and intracellular signaling were measured in myocardium and neonatal rat ventricular myocytes. Furthermore, multiple molecular methodologies were used to identify the precise molecular mechanisms underlying PDZ-RhoGEF function.

Results:
Increased PDZ-RhoGEF expression was documented in both hypertrophied hearts and neonatal rat ventricular myocytes. Upon prohypertrophic stimuli, the PDZ-RhoGEF-deficient hearts displayed alleviated cardiomyocyte enlargement and attenuated collagen deposition with improved cardiac function, whereas the adverse hypertrophic responses in hearts and neonatal rat ventricular myocytes were markedly exaggerated by PDZ-RhoGEF overexpression. Mechanistically, RhoA (ras homolog family member A)-dependent signaling pathways may function as the downstream effectors of PDZ-RhoGEF in hypertrophic remodeling, as confirmed by rescue experiments using a RhoA inhibitor and dominant-negative RhoA. Furthermore, PDZ-RhoGEF is associated with activated Gα13 and contributes to Gα13-mediated activation of RhoA-dependent signaling.

Conclusions:
Our data provide the first evidence that PDZ-RhoGEF promotes pathological cardiac hypertrophy by linking activated Gα13 to RhoA-dependent signaling pathways. Therefore, PDZ-RhoGEF has the potential to be a diagnostic marker or therapeutic target for pathological cardiac hypertrophy.
Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee
Authors: Nguyen Thanh N. , Castonguay Alicia C. , Siegler James E. , Nagel Simon , Lansberg Maarten G. , de Havenon Adam , Sheth Sunil A. , Abdalkader Mohamad , Tsai Jenny P. , Albers Gregory W. , Masoud Hesham E. , Jovin Tudor G. , Martins Sheila O. , Nogueira Raul G. , Zaidat Osama O. ,   for the SVIN GAPS Committee
Published: November 2022

Background
Recent clinical trials investigating endovascular therapy in the extended time window have opened new treatment paradigms for patients with late‐presenting large vessel occlusion stroke. The aim of this guideline is to provide up‐to‐date recommendations for the diagnosis, selection, and medical or endovascular treatment of patients with large vessel occlusion presenting in the extended time window.

Methods
The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the current literature. Recommendations were assigned by the writing group using the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Class of Recommendation/Level of Evidence algorithm and Society of Vascular and Interventional Neurology Guidelines and Practice Standards guideline format. The final guideline was approved by all members of the writing group, the Guidelines and Practice Standards committee, and the Society of Vascular and Interventional Neurology board of directors.

Results
Literature review yielded 3 high‐quality randomized trials and several observational studies that have been extracted to derive the enclosed summary recommendations. In patients with large vessel occlusion presenting in the 6‐ to 24‐hour window and with clinical–imaging mismatch as defined by the DAWN (Diffusion‐Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake‐Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) studies, endovascular therapy is recommended. Noncontrast computed tomography can be used to evaluate infarct size as the sole imaging modality for patient selection, particularly when access to computed tomography perfusion or magnetic resonance imaging is limited or if their performance would incur substantial delay to treatment. In addition, several clinical questions were reviewed based on the available evidence and consensus grading.

Conclusions
These guidelines provide practical recommendations based on recent evidence on the diagnosis, selection, and treatment of patients with large vessel occlusion stroke presenting in the extended time window.
A reviewof the application of canopy bridges in the conservation of primates and other arboreal animals across Brazil
Authors: Zimmermann Teixeira Fernanda , Gonçalves da Silva Lucas , Abra Fernanda , Rosa Clarissa , Buss Gerson , Guerreiro Marcello , Costa Edson Rodrigues , de Menezes Medeiros Aline Souza , Gordo Marcelo , Secco Helio 
Published: November 2022

Abstract
Brazil is known as a high biodiversity country, but at the same time, it has an extensive road network that threatens its wildlife and ecosystems. The impacts of roads and railways on vertebrates have been documented extensively, and the discussion concerning the implementation of mitigation measures for terrestrial wildlife has increased in the last decade. Arboreal animals are especially affected by the direct loss of individuals due to animal-vehicle collisions and by the barrier effect, because most arboreal species, especially the strictly arboreal ones, avoid going down to the ground to move across the landscape. Here we summarize and review information on existing canopy bridges across Brazil, considering artificial and natural canopy bridge initiatives implemented mainly on road and railway projects. A total of 151 canopy bridges were identified across the country, 112 of which are human-made structures of different materials, while the remaining 39 are natural canopy bridges. We found canopy bridges in three of the six biomes, with higher numbers in the Atlantic Forest and Amazon, the most forested biomes. Most of the canopy bridges are in protected areas (76%) and primates are the most common target taxa for canopy bridge implementation. Our study is the first biogeographic mapping and review of canopy bridges for arboreal wildlife conservation in a megadiverse country. We synthesize the available knowledge concerning canopy bridges in Brazil and highlight gaps that should be addressed by future research and monitoring projects.