bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of an American countermovement: Blue Lives Matter
Authors: Keyes Vance D. , Keyes Latocia 
Published: August 2022

AbstractThe social movement‐countermovement relationship is most often one of competition. The subject of police reform has become more complex after calls for greater restrictive police policies and the emergence of Blue Lives Matter. This study demonstrates how Blue Lives Matter acts as a countermovement to police reform, frame it in a historical context, explain why it appeals to sympathizers, and illustrate how it interacts with opposing groups and individuals. This study also assesses how Blue Lives Matter operates in direct opposition to Black Lives Matter and efforts for greater police accountability. The central theme of this literature addresses how the Blue Lives Matter Movement addresses competition, criticisms, and attitudes of Blue Lives Matter adherents and detractors in local and national contexts. This study questions if reconciliation between the stated objectives and tactics of the countermovement is possible without a change in police behavior and law enforcement practices. Conflict theories identify social constructionism as a process in social and countermovements.
DAMPS and complement activation in platelet concentrates that induce adverse reactions in patients
Authors: de Wit Yasmin E. S. , Hamzeh‐Cognasse Hind , Cognasse Fabrice , ten Brinke Anja , Zeerleder Sacha S. 
Published: August 2022

AbstractBackgroundPatients with severe thrombocytopenia due to bone marrow failure and after chemotherapy are still treated with platelet transfusions. Platelet concentrates (PC) are associated with a high incidence of adverse reactions (AR). Platelet‐derived damage‐associated molecular patterns (DAMPS) and complement were proposed to play a role in the pathology of AR.Study Design and MethodsSingle donor apheresis platelet concentrates (SDA PCs) were produced in a regional setting of the French Blood Establishment. After transfusion samples were collected from PC and possible AR in patients were recorded. Platelet activation markers, High mobility group box 1 (HMGB1) and complement activation products (CAP) were measured. The correlation between platelet activation, and HMGB1 and complement activation was analyzed.ResultsA total of 56 PC were included in the study. 30 PC induced no AR, and 26 induced AR (Febrile non‐hemolytic transfusion reaction n = 16; Atypical Allergic Transfusion Reactions n = 11; hemodynamic instability n = 5) in the patients. The levels of P‐selectin, sCD40L, HMGB1, C3b/c, and C4b/c were all significantly increased in PC that induced AR following transfusion in patients.Additionally, HMGB1, C3b/c, and C4b/c were positively correlated with P‐selectin and sCD40L.ConclusionIn this study, we observed an association between HMGB1 and CAP and the incidence of AR. Furthermore, we demonstrated that both HMGB1 and complement activation were correlated to platelet activation.
Supplemental Material: Don’t judge an orogen by its cover: Kinematics of the Appalachian décollement from seismic anisotropy
Authors: Frothingham Michael , al. et 
Published: August 2022

<p>Digitized structural attitudes from the Greenville 1x2° quadrangle (Nelson et al., 1998) and accompanying stereonets, CCP stacks and accompanying A1 trace profiles from SESAME D-W-lines, as well as a table of receiver function A1 arrivals with accompanying worked example and waveform plots. </p>
Irreversible
k
-Threshold Conversion Number of Circulant Graphs
Authors: Shaheen Ramy , Mahfud Suhail , Kassem Ali 
Published: August 2022

An irreversible conversion process is a dynamic process on a graph where a one-way change of state (from state 0 to state 1) is applied on the vertices if they satisfy a conversion rule that is determined at the beginning of the study. The irreversible

k

-threshold conversion process on a graph

G
=

V
,
E

is an iterative process which begins by choosing a set

S

0

⊆
V

, and for each step

t

t
=
1
,
2
,
⋯
,

,

S

t

is obtained from

S

t
−
1

by adjoining all vertices that have at least

k

neighbors in

S

t
−
1

.

S

0

is called the seed set of the

k

-threshold conversion process, and if

S

t

=
V

G

for some

t
≥
0

, then

S

0

is an irreversible

k

-threshold conversion set (IkCS) of

G

. The

k

-threshold conversion number of

G

(denoted by (

C

k

G

) is the minimum cardinality of all the IkCSs of

G
.

In this paper, we determine

C

2

G

for the circulant graph

C

n

1
,
r

when

r

is arbitrary; we also find

C

3

C

n

1
,
r

when

r
=
2
,
3

. We also introduce an upper bound for

C

3

C

n

1
,
4

. Finally, we suggest an upper bound for

C

3

C

n

1
,
r

if

n
≥
2

r
+
1

and

n
≡
0

mod

2

r
+
1

.
A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer
Authors: Nardone Agostina , Qiu Xintao , Spisak Sandor , Nagy Zsuzsanna , Feiglin Ariel , Feit Avery , Cohen Feit Gabriela , Xie Yingtian , Font-Tello Alba , Guarducci Cristina , Hermida-Prado Francisco , Syamala Sudeepa , Lim Klothilda , Munoz Gomez Miguel , Pun Matthew , Cornwell MacIntosh , Liu Weihan , Ors Aysegul , Mohammed Hisham , Cejas Paloma , Brock Jane B. , Freedman Matthew L. , Winer Eric P. , Fu Xiaoyong , Schiff Rachel , Long Henry W. , Metzger Filho Otto , Jeselsohn Rinath 
Published: August 2022

Abstract

Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1–estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1–ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1–ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

Significance:
A unique FOXA1–ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease.
See related commentary by Blawski and Toska, p. 3668
Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy
Authors: Zhang Zhuangzhuang , Cheng Lijun , Li Jie , Qiao Qi , Karki Anju , Allison Derek B. , Shaker Nuha , Li Kunyu , Utturkar Sagar M. , Atallah Lanman Nadia M. , Rao Xiongjian , Rychahou Piotr , He Daheng , Konieczny Stephen F. , Wang Chi , Shao Qing , Evers B. Mark , Liu Xiaoqi 
Published: August 2022

Abstract

Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor outcomes in patients with PDAC. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NF-κB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NF-κB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an antitumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NF-κB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC.

Significance:
Inhibition of Plk1 induces upregulation of PD-L1 expression in pancreatic ductal adenocarcinoma, stimulating antitumor immunity and sensitizing tumors to immunotherapy.
A First-in-Class Inhibitor of ER Coregulator PELP1 Targets ER+ Breast Cancer
Authors: Altwegg Kristin A. , Viswanadhapalli Suryavathi , Mann Monica , Chakravarty Dimple , Krishnan Samaya , Liu Zexuan , Liu Junhao , Pratap Uday P. , Ebrahimi Behnam , Sanchez John R. , Li Xiaonan , Ma Shihong , Park Ben H. , Santhamma Bindu , Chen Yidong , Lai Zhao , Raj Ganesh V. , Yuan Yaxia , Zhou Daohong , Sareddy Gangadhara R. , Tekmal Rajeshwar R. , McHardy Stan , Huang Tim H.-M. , Rao Manjeet K. , Vankayalapati Hariprasad , Vadlamudi Ratna K. 
Published: August 2022

Abstract

Most patients with estrogen receptor alpha–positive (ER+) breast cancers initially respond to treatment but eventually develop therapy resistance with disease progression. Overexpression of oncogenic ER coregulators, including proline, glutamic acid, and leucine-rich protein 1 (PELP1), are implicated in breast cancer progression. The lack of small molecules that inhibits PELP1 represents a major knowledge gap. Here, using a yeast-two-hybrid screen, we identified novel peptide inhibitors of PELP1 (PIP). Biochemical assays demonstrated that one of these peptides, PIP1, directly interacted with PELP1 to block PELP1 oncogenic functions. Computational modeling of PIP1 revealed key residues contributing to its activity and facilitated the development of a small-molecule inhibitor of PELP1, SMIP34, and further analyses confirmed that SMIP34 directly bound to PELP1. In breast cancer cells, SMIP34 reduced cell growth in a dose-dependent manner. SMIP34 inhibited proliferation of not only wild-type (WT) but also mutant (MT) ER+ and therapy-resistant breast cancer cells, in part by inducing PELP1 degradation via the proteasome pathway. RNA sequencing analyses showed that SMIP34 treatment altered the expression of genes associated with estrogen response, cell cycle, and apoptosis pathways. In cell line–derived and patient-derived xenografts of both WT and MT ER+ breast cancer models, SMIP34 reduced proliferation and significantly suppressed tumor progression. Collectively, these results demonstrate SMIP34 as a first-in-class inhibitor of oncogenic PELP1 signaling in advanced breast cancer.

Significance:
Development of a novel inhibitor of oncogenic PELP1 provides potential therapeutic avenues for treating therapy-resistant, advanced ER+ breast cancer.
SLFN11 Negatively Regulates Noncanonical NFκB Signaling to Promote Glioblastoma Progression
Authors: Fischietti Mariafausta , Eckerdt Frank , Perez Ricardo E. , Guillen Magaña Jamie N. , Mazewski Candice , Ho Sang , Gonzalez Christopher , Streich Lukas D. , Beauchamp Elspeth M. , Heimberger Amy B. , Baran Aneta H. , Yue Feng , James C. David , Platanias Leonidas C. 
Published: August 2022

Glioblastoma (GBM) is an aggressive and incurable brain tumor in nearly all instances, whose disease progression is driven in part by the glioma stem cell (GSC) subpopulation. Here, we explored the effects of Schlafen family member 11 (SLFN11) in the molecular, cellular, and tumor biology of GBM. CRISPR/Cas9-mediated knockout of SLFN11 inhibited GBM cell proliferation and neurosphere growth and was associated with reduced expression of progenitor/stem cell marker genes, such as NES, SOX2, and CD44. Loss of SLFN11 stimulated expression of NFκB target genes, consistent with a negative regulatory role for SLFN11 on the NFκB pathway. Furthermore, our studies identify p21 as a direct transcriptional target of NFκB2 in GBM whose expression was stimulated by loss of SLFN11. Genetic disruption of SLFN11 blocked GBM growth and significantly extended survival in an orthotopic patient-derived xenograft model. Together, our results identify SLFN11 as a novel component of signaling pathways that contribute to GBM and GSC with implications for future diagnostic and therapeutic strategies.Significance:We identify a negative regulatory role for SLFN11 in noncanonical NFκB signaling that results in suppression of the cell-cycle inhibitor p21. We provide evidence that SLFN11 contributes to regulation of stem cell markers in GBM, promoting the malignant phenotype. In addition, SLFN11 targeting triggers p21 expression and antitumor responses. Our studies define a highly novel function for SLFN11 and identify it as a potential therapeutic target for GBM.
Perceptions of Criminology and Non-Criminology Students on Management of Arms and Ammunition from Selected University in Metro Manila
Authors: Gantalao Jilmar S. 
Published: August 2022

The increasing rate of gun-related deaths in the Philippines is one of the challenging variables in the management of arms and ammunition for effective safekeeping operations. This study describes the perceptions of the students towards management or arms and ammunition, and the relationship between the profile variates of the two-groups of respondents and the level of awareness on management of arms and ammunition. This descriptive correlational research determined the perceptions of 200 students towards management or arms and ammunition, and the relationship between the profile variates of the two-groups of respondents and the level of awareness on management of arms and ammunition. A researcher-developed questionnaire was utilized. During the conduct of the study, strict ethical principles including confidentiality and non-disclosure agreement were considered. Data were analyzed using frequency, percentage distribution, mean, rank, and Pearson's correlation coefficient. Accordingly, Carrying of Firearms Outside of Residence or Place of Business has the highest mean score of 3.39, interpreted as Highly Aware, Abandoned Firearms and Ammunition, and Death or Disability of the Licensee with a mean score of 1.95, interpreted as Slightly Aware (SA). The year level , number of trainings attended , gun ownership , family monthly gross income show significant relationships to the criminology student respondents level of awareness on effective strategies in weapons and ammunition management. Further, the number of trainings attended , gun ownership , and family monthly gross income show significant relationship to the non-criminology student respondents level of awareness on management of arms and ammunition. The majority of the respondents concur that the importance of having the permit to carry firearms outside of residence or place of business issued by the Chief, PNP, or by his/her duly authorized representative to the licensed citizen allowing him/her to carry the firearm outside the residence or place of business, as such, display of firearms is prohibited. Furthermore, the year level, number of training attended, gun ownership, and family monthly gross income has a direct positive effect on the criminology student respondents level of awareness on effective strategies in weapons and ammunition management, while the number of training attended, gun ownership, and family monthly gross income has a direct positive effect on the non-criminology student respondents level of awareness on management of arms and ammunition. Therefore, school administrators should provide and recalibrate complete gun safety training to ensure those gun owners are educated on the responsible practices for handling and using firearms, storing them securely at home, as well as carrying guns in public. Further studies may be conducted on policy analysis, enforcement, and analytical methods are applied to curb firearms-related violence.
Blended Learning Modality in the New Normal Inputs Localized Learning Management System Proposal
Authors: Villasenor Ma. Vivian S. 
Published: August 2022

Blended learning is the combination of online distant learning being used in the schools. In the city where connectivity is proven, there are students who can adapt and yet there are also students who do not have a connectivity. In this way problem arises. We asked parents about this platform and from the parents themselves agreed from the school survey favored the digital modular learning. But in other localities preferred other modalities of learning. A lot of research involves teachers but seldom on the parents’ side. This is the researcher’s attempt to hear from the side of the parents and be a contributor to the effectiveness of Blended learning modality in Rizal High School.
This study aimed to determine the Blended Learning Modality in the new normal and propose an input localized learning management system in the school. Specifically, it sought to answers the following problems: 1) what is the profile of parents’ respondents in terms of the following variables: Age; Educational background; Type of Internet connection; Gadget Access at home? 2) What is the assessment of respondents in the blended learning modality of the school in terms of the following variables: Platform & Support and Governance and Challenges encountered in the blended learning modality by the group of respondents? 3.) Is there significant relationship in the assessment of parents towards blended learning modality in terms of type of internet connection they have at home? 4. What proposal from the parents as inputs in the localized blended learning modality of Rizal High School? The descriptive method of research employed in this study. The subjects of the study were the parents at Rizal High School primarily the researcher’s handled section.
Management Practices of Cooperatives: Roadmap Towards Improved Performance and Sustainability
Authors: Jumawan April R. 
Published: August 2022

The pandemic has demonstrated the cooperatives’ preparation, preparedness, and ability to respond to the needs of their members and the community. The study aimed to assess the level of management practices observed by the cooperatives and to identify constraints faced in their operations before and during the pandemic. A quantitative research method was used. Interviews were performed in person and over-the-phone. Survey questionnaires were developed and put through a pilot test. Moreover, a Google form link was provided to respondents who wished to respond online. Minitab, a statistical tool, was used to aid with all data analysis. It has been discovered that cooperatives can significantly enhance their financial performance by properly managing their working capital, capital structure, and capital budgeting. Non-financial management techniques were also significant to cooperatives’ development. This work, in particular, provides vital information for comprehending the intricacies of many topics connected to cooperative operations.
Introduction – CAI’s Contribution to International Investment Law: European, Chinese, and Global Perspectives
Authors: Chaisse Julien , Burnay Matthieu 
Published: August 2022

Abstract
The European Union and the People’s Republic of China ‘in principle’ concluded the Comprehensive Agreement on Investment (CAI). Considering that the agreement has been passed in the backdrop of dynamic multi-fora trade and investment policy-making practices, both parties’ negotiations at the bilateral, multilateral and plurilateral levels require testing. This is important to understand whether the growth of bilateral and regional agreements and the fragmentation of international economic law are enablers or roadblocks to further liberalisation of international trade and investment. This Special Issue shall analyse the CAI and argue in favour of the importance of this development. It will examine the current hyper-politicisation and geo-politicisation of investment treaties to situate the symbolic importance of the CAI. In lieu of the uncertainty of final ratification of CAI and sanctions imposed by China, this article (and the whole Special Issue it introduces) are a timely academic contribution that shall trace its scope and potential effectiveness and enable much-needed discourse.
Investment for Green Growth: An Analysis of the CAI Environmental Provisions
Authors: Qian Xu 
Published: August 2022

Abstract
Since 2012, international investment tribunals have passed several awards highlighting the interaction between environmental obligations imposed upon foreign investors and the host State’s duties towards investors in terms of green investment. The EU-China Comprehensive Agreement on Investment (CAI) is a step forward in continuing the debate on environmental protection and conservation in the context of investment law. This article focuses on section IV subsection 2 of the CAI and analyses the relevant provisions of the CAI and other Sino-EU BITs having a potential impact on the development of environmental policy and climate change-related measures. This article references publicly available investor-State arbitration decisions to understand the ramifications of environmental standards on foreign investment policymaking. Further, this article also highlights the potential impact of the CAI on green investment and green financing measures undertaken by the European Commission.
Association Between Early-Onset Osteoporosis With Hearing Loss and Benign Paroxysmal Positional Vertigo (BPPV): A Systematic Review and Meta-Analysis
Authors: García Alejandro , Rivera Sebastián , Alvear-Veas Bernardita , Goss Deborah , Castillo-Bustamante Melissa , Garcia Juan Manuel 
Published: August 2022

Objective: Osteoporosis is a chronic systemic disease characterized by low bone mass, progressive microarchitectural deterioration and increased bone fragility. Hearing loss and benign paroxysmal positional vertigo (BPPV) have been found in patients diagnosed with osteoporosis over 65 years, however, there is lack of information about these conditions in young patients. Herein, we conducted a systematic review and meta-analysis to provide evidence of the association between osteoporosis and audio-vestibular findings in young subjects. Methods: Systematic review and meta-analysis were performed according to PRISMA guidelines. Searches were conducted in PubMed, Embase, and Web of Science Core Collection. Mean age, proportion of patients with low mineral density, hearing loss, and BPPV were calculated for the systematic review and meta-analysis. Odds Ratio (OR) with their corresponding 95% confidence intervals (CI) were calculated. Results: A total of 26 articles were reviewed. Only 10 studies met inclusion criteria for the meta-analysis. Six were assessed pursuing the association between osteoporosis and hearing loss. Pooled evidence suggested in patients with osteoporosis, an increased risk for developing hearing loss (OR = 1.52, 95% CI 1.06-2.19; P = .02) compared to controls. Another 6 studies reported the association between osteoporosis and BPPV. A significant increased risk for BPPV was found in individuals with osteoporosis (OR = 1.58, 95% CI 1.02-2.4; P = .04). There was no publication bias. Conclusion: Subjects younger than 65 years with osteoporosis have an increase odds for hearing loss and BPPV compared to controls. These conditions could be associated with early inner or middle ear bone morphologic changes.