bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for an integrative review: patient and families’ perspectives on telehealth in palliative care
Authors: Bauer Eithne Hayes , Schultz Anders Nikolai Ørsted , Brandt Frans , Smith Anthony C , Bollig Georg , Dieperink Karin Brochstedt 
Published: September 2022

IntroductionIncreases in the use of telehealth in palliative care (telepalliative care) prior to, and during, the COVID-19 pandemic have resulted in a proliferation of studies on the topic. While knowledge is building on how providers and recipients adapt to telepalliative care, no reviews have, as of yet, examined telepalliative care from a patient and family perspective. Therefore, the aim of this integrative review is to explore patients and families’ perspectives on telepalliative.Methods and analysisAn integrative review will be performed inspired by the methodology of Remmington and Toronto from March 2022 to December 2022. Medline, Embase, PsycINFO and CINAHL will be searched for primary peer-reviewed studies that describe telepalliative care from patient and families’ perspectives. Limiters will be used for age; 18 years+, time; 10 years, and language; English and Danish. Hand searches of authors of included articles and reference lists of included articles will be performed. Two reviewers will independently screen and appraise selected articles using the Mixed Method Appraisal Tool. Conflicts will be resolved through discussions with a third reviewer. Data will be extracted independently by two reviewers into a data matrix with predefined headings and analysed using thematic analysis. Findings will be reported thematically, summarised into a thematic synthesis and discussed in relation to relevant literature.Ethics and disseminationEthical approval is not required for this review. Results will be published in an international peer-reviewed journal and presented at a relevant international conference. Reporting of this protocol was guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol checklist and prospectively reported to PROSPERO (CRD42022301206).
Physical health of care-experienced young children in high-income countries: a scoping review protocol
Authors: Bradford Daniel R R , Allik Mirjam , McMahon Alex D , Brown Denise 
Published: September 2022

IntroductionCare-experienced children have poorer health, developmental, and quality of life outcomes across the lifespan compared to children who are not in care. These inequities begin to manifest in the early years. The purpose of the proposed scoping review is to collate and synthesise studies of the physical health of young care-experienced children. The results of the review will help map the distribution of health outcomes, identify potential targets for intervention, and assess gaps in the literature relating to this group.Methods and analysisWe will carry out a scoping review of the literature to identify studies of physical health outcomes in care-experienced children. Systematic literature searches will be carried out on the MEDLINE, CINAHL and Web of Science Core Collection databases for items indexed on or before 31 August 2022. Studies will be included where the participants are aged 3 months or greater and less than 6 years. Data elements extracted from included studies will include study objectives, health outcomes, participant demographics, care setting characteristics and bibliographic information. The results of the review will be synthesised and reported using a critical narrative approach. Comparisons between care and non-care populations will be reported if sufficient studies are identified.Ethics and disseminationData will be extracted from publicly available sources, so no additional ethical approval is required. Results will be published in a peer-reviewed journal article. Furthermore, they will be shared in summary reports and presented to local authorities, care organisations and other relevant stakeholders that can influence healthcare policy and procedure relating to young children in care.
A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression
Authors: Deng Hui , Lin Cindy , Garcia-Gerique Laura , Fu Shuyu , Cruz Zachary , Bonner Erin E. , Rosenwasser Matthew , Rajagopal Sridharan , Sadhu M Naveen , Gajendran Chandru , Zainuddin Mohd , Gosu Ramachandraiah , Sivanandhan Dhanalakshmi , Shelef Miriam A. , Nam Brian , Vogl Dan T. , Gabrilovich Dmitry I. , Nefedova Yulia 
Published: September 2022

Abstract

Neutrophils are closely involved in the regulation of tumor progression and formation of premetastatic niches. However, the mechanisms of their involvement and therapeutic regulation of these processes remain elusive. Here, we report a critical role of neutrophil peptidylarginine deiminase 4 (PAD4) in neutrophil migration in cancer. In several transplantable and genetically engineered mouse models, tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4. Targeted deletion of PAD4 in neutrophils markedly decreased the intratumoral abundance of neutrophils and led to delayed growth of primary tumors and dramatically reduced lung metastases. PAD4-mediated neutrophil accumulation by regulating the expression of the major chemokine receptor CXCR2. PAD4 expression and activity as well as CXCR2 expression were significantly upregulated in neutrophils from patients with lung and colon cancers compared with healthy donors, and PAD4 and CXCR2 expression were positively correlated in neutrophils from patients with cancer. In tumor-bearing mice, pharmacologic inhibition of PAD4 with the novel PAD4 isoform-selective small molecule inhibitor JBI-589 resulted in reduced CXCR2 expression and blocked neutrophil chemotaxis. In mouse tumor models, targeted deletion of PAD4 in neutrophils or pharmacologic inhibition of PAD4 with JBI-589 reduced both primary tumor growth and lung metastases and substantially enhanced the effect of immune checkpoint inhibitors. Taken together, these results suggest a therapeutic potential of targeting PAD4 in cancer.

Significance:
PAD4 regulates tumor progression by promoting neutrophil migration and can be targeted with a small molecule inhibitor to suppress tumor growth and metastasis and increase efficacy of immune checkpoint blockade therapy.
VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Authors: Shields Julie A. , Meier Samuel R. , Bandi Madhavi , Mulkearns-Hubert Erin E. , Hajdari Nicole , Ferdinez Maria Dam , Engel Justin L. , Silver Daniel J. , Shen Binzhang , Zhang Wenhai , Hubert Christopher G. , Mitchell Kelly , Shakya Sajina , Zhao Shan-Chuan , Bejnood Alborz , Zhang Minjie , Tjin Tham Sjin Robert , Wilker Erik , Lathia Justin D. , Andersen Jannik N. , Chen Yingnan , Li Fang , Weber Barbara , Huang Alan , Emmanuel Natasha 
Published: September 2022

Abstract

Synthetic lethality is a genetic interaction that results in cell death when two genetic deficiencies co-occur but not when either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic–lethal interactions by virtue of their redundant functions. Here, we demonstrate a paralog-based synthetic lethality by targeting vaccinia-related kinase 1 (VRK1) in glioblastoma (GBM) deficient of VRK2, which is silenced by promoter methylation in approximately two thirds of GBM. Genetic knockdown of VRK1 in VRK2-null or VRK2-methylated cells resulted in decreased activity of the downstream substrate barrier to autointegration factor (BAF), a regulator of post-mitotic nuclear envelope formation. Reduced BAF activity following VRK1 knockdown caused nuclear lobulation, blebbing, and micronucleation, which subsequently resulted in G2–M arrest and DNA damage. The VRK1–VRK2 synthetic–lethal interaction was dependent on VRK1 kinase activity and was rescued by ectopic expression of VRK2. In VRK2-methylated GBM cell line–derived xenograft and patient-derived xenograft models, knockdown of VRK1 led to robust tumor growth inhibition. These results indicate that inhibiting VRK1 kinase activity could be a viable therapeutic strategy in VRK2-methylated GBM.

Significance:
A paralog synthetic–lethal interaction between VRK1 and VRK2 sensitizes VRK2-methylated glioblastoma to perturbation of VRK1 kinase activity, supporting VRK1 as a drug discovery target in this disease.
Abstract P027: Yamaguchi Syndrome Presenting With Atrial Fibrillation And Heart Failure Diagnosed With Contrast Echocardiography
Authors: Osman Abdul-Fatawu , Jamal Shakeel Muhammad , Banga Sandeep , Baloch Zulfiqar , Sheikh Ali 
Published: September 2022

Yamaguchi syndrome or apical hypertrophic cardiomyopathy (ApHCM), is a rare variant of hypertrophic cardiomyopathy (HCM), prevalence of about 3% among HCM population in the United States. Generally considered a benign condition but can be potentially life-threatening.
A 84 year old female with history of mitral regurgitation with mitra-clip, paroxysmal atrial fibrillation (pAF) presented to ED with dyspnea and leg swelling. She was tachypneic with bibasilar rales, jugular venous distention. BNP 1,086 pg/l with cardiomegaly and pulmonary edema on chest x-ray.
She was managed for acute decompensated cardiac failure (NYHA class III) using IV furosemide with symptom improvement. EKG revealed AF with abnormal deep T-wave inversion most prominent in precordial leads (V4-V6). Contrast echocardiogram revealed ApHCM, missed on prior echocardiograms. Patient’s dose of metoprolol was doubled, and outpatient follow-up was scheduled.

Conclusion:
ApHCM commonly presents with heart failure symptoms, chest pain, palpitation, or syncope. Undiagnosed/untreated ApHCM can lead to complications including diastolic dysfunction, left atrial enlargement causing atrial fibrillation, apical clots formation with subsequent thromboembolism, ventricular wall aneurysm, arrhythmias, and myocardial infarction. In our case, contrast echocardiogram was able to diagnose ApHCM. A presentation of heart failure symptoms at NYHA class II or higher is a known predictor of poor prognosis in patients with ApHCM. Missing diagnosis on normal echocardiogram without use of ultrasound contrast is very common. Diagnosing with proper use of modality can help to improve outcomes in these patients.
Abstract P209: Ambulatory Arterial Stiffness Index In Detecting Autonomic Failure
Authors: Khan Ghazi , Giacona John , Wang Jijia , Pittman Danielle , Vongpatanasin Wanpen 
Published: September 2022

Previous studies have shown standard deviation (SD) of daytime ambulatory systolic BP (DaySBP) as a screening tool for detecting autonomic failure. While ambulatory arterial stiffness index (AASI) has shown to be a predictor of cardiovascular morbidity and mortality, the usefulness of AASI in detecting the presence of autonomic failure has not been investigated.
We assessed AASI in 336 hypertensive and normotensive adults with and without autonomic failure (ATF). Area under receiver operator characteristic curve (AUROC) was calculated to determine accuracy of AASI in detecting ATF. Bayes factor (BF) was used to assess the significance of the difference between AUROC of AASI compared to SD daytime SBP and AASI combined with SD daytime SBP compared to SD daytime SBP alone. Sensitivity and specificity of AASI in detecting autonomic failure was derived using cut-off points from Youden’s Index.
Prevalence of ATF in our cohort was 14 % (47/336). The prevalence of HTN was 55 % (184/336). The mean age of the ATF group was higher than the control group (71 ± 11 vs. 61 ± 14 years, respectively, p < 0.05). The mean AASI of ATF patients was higher than control group (0.58 ± 0.11 vs. 0.51 ± 0.15, respectively, p < 0.05). The AUROC of AASI in ATF detection was not significantly higher than SD daytime SBP (BF =0.12). Sensitivity and specificity of AASI was 87 % and 43 %, respectively. The optimal cutoff for AASI selected by Youden’s index was 0.48. The addition of AASI to SD daytime SBP significantly improved ATF detection compared to AASI alone (BF > 3, Fig 1).
In conclusion, AASI in combination with SD DaySBP significantly outperformed AASI alone in detecting autonomic failure in patients with or without HTN.
Abstract P350: Profiling Of The Renin Angiotensin Aldosterone System In High Risk Human Pregnancy
Authors: Shoemaker Robin , Poglitsch Marko , Huang Hong , Vignes Katherine , Patel Neil , Bauer John A , O'Brien John 
Published: September 2022

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and infant morbidities and mortalities. There is a lack of clinical tools identifying subtypes of this heterogenous group of disorders, which limits optimization of individual patient care. The RAAS, a hormonal system activated during pregnancy, is suppressed in pregnancies with hypertension, but key RAAS biomarkers in subgroups of HDP have not been defined. We quantified serum biomarkers of the RAAS using LC-MS/MS in the first and third trimesters of pregnancy in a cohort of n=92 women at high-risk for preeclampsia. Data are expressed as median [IQR] of the delta of the third - first trimester. There were n=15 women that developed gestational hypertension (GH) and n=12 women that developed pre-eclampsia (Pre-e). Serum aldosterone levels increased with pregnancy in high-risk women with no adverse outcomes, but not in women that developed GH (GH, n=15: 19.4 [-321.6 - 661.6] versus Control, n=22: 502.5 [161-1019]; Data are pmol/L; P<0.01). PRA-S, a marker for activity of the RAAS that normally increases in healthy pregnancy, did not increase with pregnancy in patients that developed GH, and was further reduced in patients that developed Pre-e (GH: -17.4 [-57.1 to 2.2] versus Pre-E: -56.3 [-160.9 to -3.5] pmol/L; P<0.05). In high-risk patients that developed pre-eclampsia, aldosterone levels varied widely, depending pre-existing risk factors, such as chronic hypertension.
Serum levels of RAAS biomarkers differed by pregnancy outcome and were influenced by pre-existing risk. Declining aldosterone and PRA-S over gestation may be indicative of development of Pre-e in women with clinical risk factors for Pre-e.
Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice
Authors: Wang Xiaohua , Jiang Shan , Fei Lingyan , Dong Fang , Xie Lanyu , Qiu Xingyu , Lei Yan , Guo Jie , Zhong Ming , Ren Xiaoqiu , Yang Yi , Zhao Liang , Zhang Gensheng , Wang Honghong , Tang Chun , Yu Luyang , Liu Ruisheng , Patzak Andreas , Persson Pontus B. , Hultström Michael , Wei Qichun , Lai En Yin , Zheng Zhihua 
Published: September 2022

Background:
To provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not. Here, we test whether tacrolimus-induced hypertension involves the RhoA (Ras homolog family member A)/ROCK (Rho-associated protein kinase) pathway in male C57Bl/6 mice.

methods:
Intra-arterial blood pressure was measured under anesthesia. The reactivity of renal afferent arterioles and mesenteric arteries were assessed in vitro using microperfusion and wire myography, respectively.

Results:

Tacrolimus induced a transient rise in systolic arterial pressure that was blocked by the RhoA/ROCK inhibitor Fasudil (12.0±0.9 versus 3.2±0.7;
P
<0.001). Moreover, tacrolimus reduced the glomerular filtration rate, which was also prevented by Fasudil (187±20 versus 281±8.5;
P
<0.001). Interestingly, tacrolimus enhanced the sensitivity of afferent arterioles and mesenteric arteries to Ang II (angiotensin II), likely due to increased intracellular Ca
2+
mobilization and sensitization. Fasudil prevented increased Ang II-sensitivity and blocked Ca
2+
mobilization and sensitization. Preincubation of mouse aortic vascular smooth muscle cells with tacrolimus activated the RhoA/ROCK/MYPT-1 (myosin phosphatase targeting subunit 1) pathway. Further, tacrolimus increased cytoplasmic reactive oxygen species generation in afferent arterioles (107±5.9 versus 163±6.4;
P
<0.001) and in cultured mouse aortic vascular smooth muscle cells (100±7.5 versus 160±23.2;
P
<0.01). Finally, the reactive oxygen species scavenger Tempol inhibited tacrolimus-induced Ang II hypersensitivity in afferent arterioles and mesenteric arteries.

Conclusions:
The RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing Ang II-specific vasoconstriction, and reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.
Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis
Authors: Saha Piu , Mell Blair , Golonka Rachel M. , Bovilla Venugopal R. , Abokor Ahmed A. , Mei Xue , Yeoh Beng San , Doris Peter A. , Gewirtz Andrew T. , Joe Bina , Vijay-Kumar Matam 
Published: September 2022

Background:
The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.

methods:

IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and
pIgR
(polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin).

Results:

Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver
pIgR
expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA
+
B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP.

Conclusions:
This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
Angiotensin Receptor Blockers Are Associated With a Lower Risk of Progression From Mild Cognitive Impairment to Dementia
Authors: Deng Zhenhong , Jiang Jingru , Wang Jia , Pan Dong , Zhu Yingying , Li Honghong , Zhang Xiaoni , Liu Xiaohuan , Xu Yongteng , Li Yi , Tang Yamei ,   for the Alzheimer’s Disease Neuroimaging Initiative†
Published: September 2022

Background:
Previous studies found that antihypertensive medications (AHMs) acting on the renin-angiotensin system had the potential to reduce the progression from mild cognitive impairment to dementia. However, it remains unclear whether this association differs between ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers.

methods:
We conducted a retrospective cohort study in the Alzheimer’s Disease Neuroimaging Initiative among 403 participants with hypertension and mild cognitive impairment at baseline. Information on AHMs received during the follow-up period, including angiotensin receptor blockers, ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics, were self-reported. Cox proportional hazards models adjusted for potential confounders were used in the time to event analysis with progression to dementia as outcome.

Results:

Of the 403 participants, the mean (SD) age was 74.0 (7.3) years, 152 (37.7%) were female, 158 (39.2%) progressed to dementia over a median follow-up time of 3.0 years. Angiotensin receptor blockers were associated with a lower risk of progression to dementia as compared to ACE inhibitors (adjusted hazard ratio=0.45 [95% CI, 0.25–0.81];
P
=0.023), other classes of AHMs (beta-blockers, calcium channel blockers, diuretics; adjusted hazard ratio, 0.49 [95% CI, 0.27–0.89];
P
=0.037), and none of AHMs (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.58];
P
=0.001).

Conclusions:
In patients with hypertension and mild cognitive impairment, angiotensin receptor blockers were associated with a lower risk of progression to dementia compared with ACE inhibitors and other classes of AHMs. Our findings may have important implications for clinical practice but still warrant further investigations in larger prospective cohorts or clinical trials.
Effect of Financial Incentives on Hypertension Control: A Multicenter Randomized Controlled Trial in China
Authors: Zheng Liqiang , Liu Sitong , Jiao Yundi , Wu Yani , Wang Yali , Yu Zhecong , Xu Jiahui , Sun Yingxian , Sun Zhaoqing 
Published: September 2022

Background:
Poorly controlled hypertension is a great challenge to global public health. Incentive approaches, based on behavioral and economic concepts, may improve patients’ adherence to treatment.

methods:
We conducted a 2-arm randomized controlled trial to test whether financial incentives can help patients with poorly controlled hypertension in China reduce their blood pressure (BP). Participants were randomized 1:1 to the control and intervention groups. All participants received WeChat-based standard education and support for hypertension management. The intervention group received financial incentives, including process- and outcome-based incentives.

Results:

No statistically significant differences in BP reduction and hypertension control rates were found between the two groups from baseline to 12-month follow-up. Mean systolic BP decreased from 158.7 to 149.8 mm Hg in the intervention group and 159.7 to 149.5 mm Hg in the control group (
P
=0.639). Mean diastolic BP decreased from 93.7 to 86.6 mm Hg in the intervention group and 93.9 to 86.3 mm Hg in the control group (
P
=0.667). Hypertension control rates in the intervention and control groups were 20.8% and 15.8%, respectively (
P
=0.318). Medication adherence was 84.2% in the intervention group and 86.2% in the control group (
P
=0.705).

Conclusions:
Financial incentives were effective in the short term for BP control, but a sustained effect of incentive-based BP control was not identified beyond 3 months of intervention. Future studies that focus on identifying the appropriate amount and structure of financial incentives for BP control are warranted.

Registration:

URL:
www.isrctn.org
; Unique identifier: ISRCTN13467677.
Peasant Studies in the Journal Modern China, 1979–1991
Authors: Li (李松) Song , Wu (吴煌琨) Huangkun , Liu (刘苹) Ping 
Published: September 2022

Abstract
From 1979 to 1991, Modern China, a landmark journal of Chinese studies, published a large number of articles in the field of peasant studies. These articles are of two types: studies of peasants in premodern China, which focus on the rural economy, politics, and ideology; and studies on the history of “peasant studies” itself, which focus on the problems, paradigms and directions of the field. Taken together, all these articles reveal the influence of three major approaches to history: the longue durée perspective of the French Annales school, the “bottom-up” approach to lived experience of the British new social history movement, and the time, space, and demography frame of reference of G. William Skinner.