bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice
Authors: Wang Jinxi , Shi Qian , Wang Yihui , Dawson Logan W. , Ciampa Grace , Zhao Weiyang , Zhang Guangqin , Chen Biyi , Weiss Robert M. , Grueter Chad E. , Hall Duane D. , Song Long-Sheng 
Published: March 2022

Background:
Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby JP2 (junctophilin-2), an essential component of the excitation-contraction coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT [N-terminal fragment of JP2]) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes. This study aims to determine whether JP2NT can be leveraged by gene therapy techniques for attenuating HF progression in a preclinical pressure overload model.

Methods:

We intraventricularly injected adeno-associated virus (AAV) (2/9) vectors expressing eGFP (enhanced green fluorescent protein), JP2NT, or DNA-binding deficient JP2NT (JP2NT
ΔbNLS/ARR
) into neonatal mice and induced cardiac stress by transaortic constriction (TAC) 9 weeks later. We also treated mice with established moderate HF from TAC stress with either AAV-JP2NT or AAV-eGFP. RNA-sequencing analysis was used to reveal changes in hypertrophic and HF-related gene transcription by JP2NT gene therapy after TAC. Echocardiography, confocal imaging, and histology were performed to evaluate heart function and pathological myocardial remodeling following stress.

Results:
Mice preinjected with AAV-JP2NT exhibited ameliorated cardiac remodeling following TAC. The JP2NT DNA-binding domain is required for cardioprotection as its deletion within the AAV-JP2NT vector prevented improvement in TAC-induced cardiac dysfunction. Functional and histological data suggest that JP2NT gene therapy after the onset of cardiac dysfunction is effective at slowing the progression of HF. RNA-sequencing analysis further revealed a broad reversal of hypertrophic and HF-related gene transcription by JP2NT overexpression after TAC.

Conclusions:
Our prevention- and intervention-based approaches here demonstrated that AAV-mediated delivery of JP2NT into the myocardium can attenuate stress-induced transcriptional remodeling and the development of HF when administered either before or after cardiac stress initiation. Our data indicate that JP2NT gene therapy holds great potential as a novel therapeutic for treating hypertrophy and HF.
Novel CaMKII-δ Inhibitor Hesperadin Exerts Dual Functions to Ameliorate Cardiac Ischemia/Reperfusion Injury and Inhibit Tumor Growth
Authors: Zhang Junxia , Liang Ruqi , Wang Kai , Zhang Wenjia , Zhang Mao , Jin Li , Xie Peng , Zheng Wen , Shang Haibao , Hu Qingmei , Li Jiayi , Chen Gengjia , Wu Fujian , Lan Feng , Wang Lipeng , Wang Shi-Qiang , Li Yongfeng , Zhang Yong , Liu Jinghao , Lv Fengxiang , Hu Xinli , Xiao Rui-Ping , Lei Xiaoguang , Zhang Yan 
Published: March 2022

Background:

Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca
2+
/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart.

Methods:
A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin.

Results:
Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9–induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell–derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury.

Conclusions:
Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.
The Charism of Care of the Order of St John and Female Monasticism
Authors: Dulska Anna Katarzyna 
Published: March 2022

Abstract
The charism of care inspired the foundation of various medieval religious orders, the Order of St John of Jerusalem being the most renowned of these. This article uses a case study of a female Hospitaller convent in Bargota in the kingdom of Navarre, to examine to what extent the charism of hospitality influenced the Order’s decision-making. By identifying the factors lying behind the foundation of the convent in the early fourteenth century and its dissolution a century later, it contributes to the discussion on the relevance of female Hospitaller monasticism in the Late Middle Ages and argues that the Order sustained the convent as long as the women’s care-worthiness outweighed the burden of cura monialium.
Sufism, Miracles and Oceanic Fatwas: The Beloved of North Jakarta
Authors: Sevea Teren 
Published: March 2022

Abstract
This article examines stories, hagiographies, fatwas, and treatises related to the grave of a sayyid miracle worker (keramat) buried in North Jakarta. It is a product of research that began in 2008 when I first visited the Sufi shrine of the eminent keramat, Habib Hussein al-ʿAydarus (d. 1169/1756), in the village of Luar Batang. Herefrom, I enjoyed access to a series of documents, oral traditions and miracle stories, along with invaluable information via conversations with Sufi elders, devotees, and Habib Hussein’s kinsmen. This article begins by introducing the Luar Batang shrine and stories of the keramat’s apparitions that continue to be told in the village. It discusses a twenty-first century moment when the keramat was seen by some to resist urban redevelopment and collude with controversial Islamists and Sunni vigilantes. His apparitions and miracle stories reminded votaries of his immortal history of resisting colonialism, secularism, Islamophobia and ‘Christianisation’. From this contemporary moment, the article turns its attention towards hagiographies produced in twentieth-century Java by the historians of Sufi networks, before analysing fatwas on the keramat produced in the late nineteenth century by Islamic scholars (ulama) from Yemen, Mecca, Medina and Java concerning revenue, inheritance, and the legality of customs at the Luar Batang shrine. The article works backwards from a contemporary moment in order to introduce readers to the keramat, village and grave and his historical and peripatetic life in Gujarat, Hadramaut and Java, before highlighting how the shrine of a seemingly peripheral village in Jakarta has been a key concern for authorities across the Islamic world and an Indian Ocean-wide devotional community. Miracle stories and hagiographies praising the keramat as the exemplar of Sunnism and Shafiʿism, as well as fatwas defending the customs of his shrine as being inviolable ones, encourage us to discard the still-regnant academic divisions of Sharia/Custom and Sufis/Ulama. Together, they tell a story of miraculous narratives, devotional cultures, social memories and sacral places that are often pushed to the margins of religious studies but refuse to fade into oblivion.
«The Matter Present in Sensibles but not qua Sensibles». Aristotle’s Account of Intelligible Matter as the Matter of Mathematical Objects
Authors: Michetti Beatrice 
Published: March 2022

AbstractAristotle explicitly speaks of intelligible matter in three passages only, all from theMetaphysics, in the context of the analysis of definition as the formula that expresses the essence:Metaph.Z10, 1036 a8-11;Metaph.Z11, 1037 a5;Metaph.H6, 1045 a34-36 and 45 b1. In the case of the occurrences of Z10 and Z11, there is almost unanimous consensus that Aristotle uses the expression in a technical way, to indicate the matter of that particular type of objects that are intelligible compounds, of which mathematical objects are paradigmatic instances. By contrast, there is no agreement on how to understand the expression in the case of H6. Here, ‘intelligible matter’ would denote, as stated by some interpreters, the generic element of the definition. The aim of this paper is to show that ὕλη νοητή has the same technical meaning in all the three explicit occurrences in theMetaphisics. Contrary to the interpretation that there is a shift in meaning from Z10-11 to H6, my goal is to illustrate that in both contexts, Aristotle uses the expression ‘intelligible matter’ to designate the matter of mathematical objects insofar as they are paradigmatic intelligible compounds.
Dialectic and Sophisms: The Sceptical Dissolution of Dogmatic Logic
Authors: Spinelli Emidio 
Published: March 2022

Abstract
This paper aims to examine a very specific passage of Sextus Empiricus’s work: the final section of the second book of the Outlines of Pyrrhonism (=ph ii, 229–259). Here Sextus concentrates his attention on a very limited yet crucial topic, namely the question of the validity or invalidity and ‘pragmatic dissolution’ of an allegedly strong tool such as sophisms and their dialectical structure. Indeed, Pyrrhonists do not wander about aimlessly nor lack effective tools through which to dismantle the logical industry of sophisms; their reference point is completely different, since they agree about some evident facts and live their life in accordance with κοινὸς βίος.
Keep it Simple, Laboratory Parameters to Predict Complicated Acute Appendicitis in Children Younger Than Five Years
Authors: Hazan Danny , Goldstein Adam Lee , Keidar Sergey , Dayan Katia , Shimonov Mordechai 
Published: March 2022

Background The clinical presentation of acute appendicitis in the youngest age lacks specific signs and symptoms, and it is difficult to obtain an accurate clinical diagnosis. Once the diagnosis is made, it is necessary to determine if the appendicitis is simple and able to be managed non-surgically, or complicated, therefore requiring surgery. Together with the clinical picture and imaging, routine laboratory values play a vital role in this decision. The aim of this study is to evaluate routine blood in their ability to differentiate between complicated and uncomplicated acute appendicitis. Method A retrospective analysis was conducted from a single pediatric surgery department of all children 5 years of age or younger who underwent surgery for acute appendicitis between the years 2010-2020. Results 728 children were diagnosed with acute appendicitis, and 42 children were under the age of 5 years. There was a significant difference in the C-reactive protein, white blood cell count, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio in the complicated group versus the uncomplicated group. The value of these together for prediction complicated appendicitis were 84.8% sensitivity, 80.9% specificity, 82.8% positive predictive value, and 72.8% negative predictive value. These values were all higher than both the Alvarado score and the PAS ( P  <  .05). Conclusions C-reactive protein, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio are simple laboratory parameters that can help identify complicated versus uncomplicated appendicitis in children 5 years old or younger. These universal parameters may help guide the treatment and decision to operate on a difficult to diagnose population.
Quality of Public Services in the Era of Guaranteed Public Service Delivery
Authors: Pareek Urvashi , Sole Nagendra Ambedkar 
Published: March 2022

The provision of public services is one of the important functions performed by a government as it ensures the growth of a nation and promotes welfare and justice in society. Public services are characterised by timeliness, quality and grievance redressal in the course of service delivery. Quality is an important component of public service delivery and determines citizens’ satisfaction and trust in the government. The debates on governance during the 1990s were focused on service delivery as the most important component in the governance process. Public services were seen as a medium for interaction between the citizens and the government through street-level agents of the state to promote the welfare and wellbeing of the people. Developments like the Citizen’s Charter formulation and implementation, social audit, e-Governance programme, Public Service Guarantee Act, and so on have shaped the governance discourse in India. This essay highlights the significance of quality in public service delivery in India, its need the quality-satisfaction-trust triad, barriers to quality in public service delivery, tools to ensure the quality of public services in India and international best practices.
Variations in mortality in Medicare recipients on extracorporeal membrane oxygenation
Authors: Agbafe Victor , Fugett James , Gall Ashley , Dhamija Ankit , Asad Fatima , Abbas Kamil , Hayanga Jeremiah A 
Published: March 2022

Background Extracorporeal membrane oxygenation (ECMO) is a rescue modality against severe cardiac and pulmonary compromise. We sought to assess variation in mortality and associated environmental and infrastructural predictors among Medicare beneficiaries on ECMO. Methods We used Medicare claims data to evaluate hospitalizations between 2017 and 2019 during which beneficiaries required ECMO. The primary outcome of interest was mortality. We evaluated the influence on mortality of Medicare Case Mix Index (CMI), Medicare Wage Index, hospital size, ECMO cannulations, cardiology volume, region, and gender and modeled necessity and sufficiency relations involving ECMO volume, hospital size, cardiology volume, US region, and the mortality index through qualitative comparative analysis (QCA). Results 5368 ECMO cases were performed at 306 hospitals. Compared to institutions with a mortality index equal to or below 2, those above this threshold had statistically significant higher number of beds, cardiology volumes, and lower survival percentages ( p < 0.05). Moreover, we observed a smaller proportion of institutions with an ECMO volume < 20 (78.3% vs 63.4%), which had mortality index > 2. The QCA analysis indicated that low cardiology volume and central/east location are necessary but not sufficient conditions for a mortality index above 2. Conclusion Trends in mortality are influenced by prevailing socioeconomic, utilization, infrastructural characteristics, and volume. As such, ECMO mortality may be more accurately predicted by models that account for more factors than clinical parameters alone.
Reoperation rate of ductal carcinoma in situ: impact of tomosynthesis (3D) and spot magnification
Authors: Arlan Kirill , Meretoja Tuomo J , Hukkinen Katja 
Published: March 2022

Background Surgical planning depends on precise preoperative assessment of the radiological extent of ductal carcinoma in situ (DCIS). Despite different modalities used, reoperation rates for DCIS due to involved margins are high. Purpose To evaluate the impact of additional imaging views (spot magnification, tomosynthesis) on surgical reoperation rate of DCIS. Material and Methods The retrospective single institute study includes 157 patients with biopsy-proven pure DCIS seen on mammogram as microcalcifications and treated with breast-conserving surgery. Patients have been divided into three groups according to additional imaging performed: spot magnification, tomosynthesis, and none. All breast images (mammograms, spot magnification, tomosynthesis) were reviewed and the maximum extent of pathological microcalcifications was recorded. Radiological size was compared to final histopathological size. Reoperation rate due to inadequate margins was recorded. Results Reoperation rates (25%) due to inadequate margins were as follows: spot (18%), tomosynthesis (27%), none (31%); P = 0.488. Spot magnification, tomosynthesis, and digital zoom of full-field digital mammography predicted similarly the final histopathological size. Reoperation group had a significantly greater preoperative radiological median size (26 mm vs. 20 mm; P = 0.014) as well as median size of disease on final histopathological report (29 mm vs. 14 mm; P < 0.001). Discrepancy between radiological and final histopathological size became greater with increasing DCIS extent. Conclusion The main factors for reoperations are DCIS size and discordance between radiological and histopathological sizes. The use of additional imaging views (spot magnification, tomosynthesis) did not reduce reoperation rate.
Promotion of dermal tissue engineering in a rat model using a composite 3D-printed scaffold with electrospun nanofibers and recipient-site preconditioning with an external volume expansion device
Authors: Choi Hae Woon , Hong Jamin , Kim Junhyung , Jeong Woonhyeok , Jo Taehee , Lee Hyoun Wook , Park Sang Woo , Choi Jaehoon 
Published: March 2022

We hypothesized that use of a composite three-dimensionally (3D) printed scaffold with electrospun nanofibers in conjunction with recipient-site preconditioning with an external volume expansion (EVE) device would enable successful dermal tissue regeneration of a synthetic polymer scaffold. Cell viability, cell infiltration, extracellular matrix deposition, scaffold contraction, and mRNA expression by dermal fibroblasts cultured on three different scaffolds, namely, 3D-printed scaffold with a collagen coating, 3D-printed scaffold with an electrospun polycaprolactone nanofiber and collagen coating, and 3D-printed scaffold with an electrospun polycaprolactone/collagen nanofiber, were measured. Before scaffold implantation, rats were treated for 2 h with an EVE device to evaluate the effect of this device on the recipient site. Cell proliferation rates were significantly higher on the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating than on the other scaffolds. In cell invasion studies, the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating showed better cell integration than the other scaffolds. Under stereomicroscopy, fibroblasts adhered tightly to the electrospun area, and the fibroblasts effectively produced both collagen and elastin. Rat skin treated with an EVE device exhibited increased HIF-1α protein expression and capillary neoformation compared with control skin. Invasion of CD8+ cytotoxic lymphocytes surrounding the scaffold decreased when the recipient site was preconditioned with the EVE device. The composite 3D printed scaffold with electrospun nanofibers provided a favorable environment for proliferation, migration, and extracellular matrix synthesis by fibroblasts. Recipient-site preconditioning with an EVE device allowed for scaffold incorporation with less inflammation due to improved angiogenesis.
Views of Nurses, Obstetricians, and Mothers Regarding Independent Nurse-Midwifery Practitioner: A Mixed-Method Study
Authors: Yadav Raksha , Jelly Prasuna , Sharma Suresh K. , Sharma Rakesh 
Published: March 2022

Background: The maternal and neonatal health indicators in India are not getting better despite various national schemes and interventional programs. The main reason is nonaccess to the primary care services by the people at the grass-root level, mainly due to lack of trained health-care resources. Objective: Therefore, this study aimed to explore the perception, scope of practice, and perceived barriers of independent nurse midwifery practitioner (INMP) among nurses, obstetricians, and postnatal mothers. Materials and Methods: A convergent parallel, mixed-method design was used in this study. Quantitative data were collected by using a self-structured, 5-point Likert scale to assess perception and perceived barriers; and a structured opinionnaire to explore the perceived scope of practice of INMP from 260 nurses, obstetricians, and mothers. A semi-structured interview was conducted for qualitative data from 48 study participants. Quantitative data were analyzed by descriptive and inferential statistics (Kruskal Wallis test), and RQDA software was used for qualitative data analysis. Results: The results show that the participants have favorable perceptions about INMP. The majority believed that INMPs could do most of the tasks as per recommendations about their scope of practice with few limitations. Though, there might be collaboration issues and role conflicts between obstetricians and INMPs initially. Participants also identified various ways to overcome the barriers for INMP. Conclusion: This study revealed that there is a dire need for INMPs in developing countries like India. Overall, participants felt that INMPs would be successful to practice in India if the government comes up with such cadre in the future.