bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of whole-genome sequencing in patients with early-onset dementia
Authors: Huq Aamira J , Thompson Bryony , Bennett Mark F , Bournazos Adam , Bommireddipalli Shobhana , Gorelik Alexandra , Schultz Joshua , Sexton Adrienne , Purvis Rebecca , West Kirsty , Cotter Megan , Valente Giulia , Hughes Andrew , Riaz Moeen , Walsh Maie , Farrand Sarah , Loi Samantha M , Kilpatrick Trevor , Brodtmann Amy , Darby David , Eratne Dhamidhu , Walterfang Mark , Delatycki Martin Bruce , Storey Elsdon , Fahey Michael , Cooper Sandra , Lacaze Paul , Masters Colin L , Velakoulis Dennis , Bahlo Melanie , James Paul A , Winship Ingrid 
Published: July 2022

BackgroundIn the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation.MethodsWGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer’s disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD.ResultsClinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified aC9orf72expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk.DiscussionWGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.
Endovascular treatment of ruptured anterior communicating aneurysms: a 17-year institutional experience with coil embolization
Authors: Catapano Joshua S , Karahalios Katherine , Rumalla Kavelin , Srinivasan Visish M , Rutledge Caleb , Baranoski Jacob F , Cole Tyler S , Jadhav Ashutosh P , Ducruet Andrew F , Albuquerque Felipe C 
Published: July 2022

BackgroundRuptured anterior communicating artery (ACoA) aneurysms can be challenging to treat via an endovascular procedure. This study analyzed retreatment rates and neurological outcomes associated with ruptured ACoA aneurysms treated via endovascular coiling.MethodsAll patients with a ruptured ACoA aneurysm treated with endovascular coiling from 2003 to 2019 were retrospectively analyzed at a single center. Two comparisons were performed: no retreatment versus retreatment and coil embolization versus balloon-assisted coil embolization. Outcomes included retreatment and neurological outcome assessed via modified Rankin Scale (mRS).ResultsDuring the study period, 186 patients with ruptured ACoA aneurysms underwent coil embolization. Treatment included standard coil embolization (68.3%, n=127), balloon-assisted coiling (28.5%, n=53), and stent-assisted embolization (2.7%, n=5). Angiographic outcomes were as follows: class I, 65.1% (n=121); class II, 28.5% (n=53); and class III, 6.5% (n=12). There were no aneurysm reruptures after the index procedure. The mean (SD) mRS score was 2.7 (2.0) at last follow-up (mortality, 19 (10%)). Retreatment occurred in 9.7% (n=18). Patients with retreatment were younger with lower-grade subarachnoid hemorrhage and more favorable functional status at discharge. Patients with aneurysms >7 mm (n=36) were significantly more likely to have recurrence (22.2% vs 6.7%, P=0.005).ConclusionsEndovascular treatment of ruptured ACoA aneurysms is safe and is associated with low mortality and retreatment rates. Younger patients with favorable functional status and larger aneurysm size are more likely to be retreated. Ruptured aneurysms <4 mm, although prevalent in the study (29%), never required retreatment.
Business Model Innovation to Address Vegetable Supply Chain Issues: A Case Study of an Indian Startup
Authors: Sharma A. , Deshmukh Sagar Surendra , Ojha Ankur 
Published: July 2022

Purpose: Agricultural supply chains witness several challenges, which result in increased cost of operations, high wastages, and low efficiency. In the case of vegetable supply chains (VSCs), the intensity of challenges is very high due to perishability. Literature suggests various operations research tools for supply chain management of perishables, but there is a paucity of research highlighting the real models adopted by real players in the market while making revenue. This paper investigates and presents how a startup can innovate its business model to meet the VSC issues by adopting a single case study methodology. Design: The phenomenon was studied by convergent interviewing with the company’s key personnel and gathering information from the company’s key documents followed by content analysis. Findings: The study shows real practices adopted by a startup to cater to the challenges of VSCs in India by incorporating various tools of productivity enhancement and waste reduction. It highlights the adoption of a traceability system, production planning mechanism, reduced food miles, and green initiatives contributing to an innovative business model. The study maps the business model of the startup with the business model concept provided by Lindgardt and colleagues [ 2009 ] and states two more dimensions, i.e. “Client relationship management” and “Sustainability activities” to expand the mentioned configuration. Originality: The study is the first of its kind to highlight the Business Model Innovation of a startup to address the VSC challenges in the Indian context. Practical contribution: The study has important managerial implications useful for finding our new value propositions in a VSC firm by shortening and effectively integrating the supply chain while minimizing information asymmetry to achieve economies and sustainability. Theoretical contribution: This study has strengthened the methodological advances in the study of business models based upon earlier validated configurations. It contributes to the extant research by adding two more elements “Client relationship management” and “Sustainability activities” in a business model configuration.
Alteration of Plasma Amino Acid Concentrations in Iranian Children with COVID-19
Authors: Shams Sedigheh , Azari-Yam Aileen , Safavi Moeinadin , Zamani Zahra , Sotoudeh-Anvari Maryam , Sharifzadeh Ekbatani Meisam , Haghi-Ashtiani Mohammad-Taghi , Mozafari Fatemeh , Yaghmaie Bahareh , Shafeghat Leila 
Published: July 2022

COVID-19 is an acute viral disease that has so far infected more than 200 million and killed more than four million worldwide. It affects the immune system and other organs. Here, we investigated the level of free plasma amino acids in COVID-19 patients and compared them with non-COVID-19 subjects. We also compared amino acids levels in critically ill patients admitted to the intensive care unit (ICU) with non-ICU patients and expired and recovered patients. Twenty-six COVID-19 patients and 32 non-COVID-19 subjects were included in the study. The mean of glutamic acid, serine, glycine, threonine, phenylalanine, leucine, lysine, alanine, arginine, aspartic acid, and ornithine was significantly higher in cases than controls. In addition, the mean of glutamine was significantly lower in patients than controls (

443.89
±
254.31

vs.

651.73
±
107.38

,

PV
<
0.001

). Low level of glutamine and isoleucine was seen in the majority of ICU and expired patients, respectively. Logistic regression analysis showed low level of isoleucine as a predictor variable in mortality (

P
=
0.02

,

EXP

B

=
16.5

, and

CI

95
%
=

1.48

,

−

183.07

). There was a positive and significant relationship between some amino acids levels, serum liver enzymes, and sodium concentrations. There was also a significant but negative correlation between histidine levels, ESR, and ferritin. Phenylalanine had a highly positive relationship with serum procalcitonin in patients (

R

2

=
0.534

,

PV
=
0.015

). Our studies have shown the alteration of plasma amino acids concentration in COVID-19 patients. These changes are more evident in critically ill and at-risk patients.
Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation
Authors: Chen Sisi , Vedula Rahul S. , Cuevas-Navarro Antonio , Lu Bin , Hogg Simon J. , Wang Eric , Benbarche Salima , Knorr Katherine , Kim Won Jun , Stanley Robert F. , Cho Hana , Erickson Caroline , Singer Michael , Cui Dan , Tittley Steven , Durham Benjamin H. , Pavletich Tatiana S. , Fiala Elise , Walsh Michael F. , Inoue Daichi , Monette Sebastien , Taylor Justin , Rosen Neal , McCormick Frank , Lindsley R. Coleman , Castel Pau , Abdel-Wahab Omar 
Published: July 2022

Abstract

Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted in the discovery of LZTR1 as an adapter of a Cullin-3 RING E3 ubiquitin ligase complex responsible for the degradation of RAS GTPases. In parallel, dysregulated LZTR1 expression via aberrant splicing and mutations was identified in clonal hematopoietic conditions. Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 that escape degradation, drives hematopoietic stem cell (HSC) expansion and leukemia in vivo. Although RIT1 stabilization was sufficient to drive hematopoietic transformation, transformation mediated by LZTR1 loss required MRAS. Proteolysis targeting chimeras (PROTAC) against RAS or reduction of GTP-loaded RAS overcomes LZTR1 loss-mediated resistance to FLT3 inhibitors. These data reveal proteolysis of noncanonical RAS proteins as novel regulators of HSC self-renewal, define the function of RIT1 and LZTR1 mutations in leukemia, and identify means to overcome drug resistance due to LZTR1 downregulation.

Significance:
Here we identify that impairing proteolysis of the noncanonical RAS GTPases RIT1 and MRAS via LZTR1 downregulation or leukemia-associated mutations stabilizing RIT1 enhances MAP kinase activation and drives leukemogenesis. Reducing the abundance of GTP-bound KRAS and NRAS overcomes the resistance to FLT3 kinase inhibitors associated with LZTR1 downregulation in leukemia.
This article is highlighted in the In This Issue feature, p. 2221
Sodium‐Glucose Cotransporter 2 Inhibitor Canagliflozin Antagonizes Salt‐Sensitive Hypertension Through Modifying Transient Receptor Potential Channels 3 Mediated Vascular Calcium Handling
Authors: Zhao Yu , Li Li , Lu Zongshi , Hu Yingru , Zhang Hexuan , Sun Fang , Li Qiang , He Chengkang , Shu Wentao , Wang Lijuan , Cao Tingbing , Luo Zhidan , Yan Zhencheng , Liu Daoyan , Gao Peng , Zhu Zhiming 
Published: July 2022

Background
Salt‐sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium‐glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive.

Methods and Results
Dahl salt‐sensitive rats and salt‐insensitive controls were fed with 8% high‐salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high‐salt‐induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt‐sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high‐salt diet. High salt intake increased vascular expression of TRPC3 in salt‐sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt‐induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high‐salt‐induced activation of NCX1 (sodium‐calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin.

Conclusions
We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high‐salt‐induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt‐sensitive hypertension.
Identification of Distinct Subgroups in Moderately Severe Rheumatic Mitral Stenosis Using Data‐Driven Phenotyping of Longitudinal Hemodynamic Progression
Authors: Ko Kyu‐Yong , Cho Iksung , Kim Subin , Seong Yeonchan , Kim Dae‐Young , Seo Ji Won , You Seng Chan , Shim Chi Young , Hong Geu‐Ru , Ha Jong‐Won 
Published: July 2022

Background
Rheumatic mitral stenosis is a significant cause of valvular heart disease. Pulmonary arterial systolic pressure (PASP) reflects the hemodynamic consequences of mitral stenosis and is used to determine treatment strategies. However, PASP progression and expected outcomes based on PASP changes in patients with moderately severe mitral stenosis remain unclear.

Methods and Results

A total of 436 patients with moderately severe rheumatic mitral stenosis (valve area 1.0–1.5 cm
2
) were enrolled. Composite outcomes included all‐cause mortality and hospitalization for heart failure. Data‐driven phenotyping identified 2 distinct trajectory groups based on PASP progression: rapid (8.7%) and slow (91.3%). Patients in the rapid progression group were older and had more diabetes and atrial fibrillation than those in the slow progression group (all
P
<0.05). The initial mean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group (6.2±2.4 mm Hg versus 5.1±2.0 mm Hg [
P
=0.001] and 42.3±13.3 mm Hg versus 33.0±9.2 mm Hg [
P
<0.001], respectively). The rapid progression group had a poorer event‐free survival rate than the slow progression group (log‐rank
P
<0.001). Rapid PASP progression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio, 3.08 [95% CI, 1.68–5.64];
P
<0.001). Multivariate regression analysis revealed that PASP >40 mm Hg was independently associated with allocation to the rapid progression group (odds ratio, 4.95 [95% CI, 2.08–11.99];
P
<0.001).

Conclusions
Rapid PASP progression was associated with a higher risk of the composite outcomes. The main independent predictor for rapid progression group allocation was initial PASP >40 mm Hg.
Predictors and Outcomes of Heart Failure With Preserved Ejection Fraction in Patients With a Left Ventricular Ejection Fraction Above or Below 60%
Authors: Nakagawa Akito , Yasumura Yoshio , Yoshida Chikako , Okumura Takahiro , Tateishi Jun , Yoshida Junichi , Seo Masahiro , Yano Masamichi , Hayashi Takaharu , Nakagawa Yusuke , Tamaki Shunsuke , Yamada Takahisa , Kurakami Hiroyuki , Sotomi Yohei , Nakatani Daisaku , Hikoso Shungo , Sakata Yasushi ,   the Osaka CardioVascular Conference (OCVC)‐Heart Failure Investigators
Published: July 2022

Background
Although potential therapeutic candidates for heart failure with preserved ejection fraction (HFpEF) are emerging, it is still unclear whether they will be effective in patients with left ventricular ejection fraction (LVEF) of 60% or higher. Our aim was to identify the clinical characteristics of these patients with HFpEF by comparing them to patients with LVEF below 60%.

Methods and Results

From a multicenter, prospective, observational cohort (PURSUIT‐HFpEF [Prospective Multicenter Obsevational Study of Patients with Heart Failure with Preserved Ejection Fraction]), we investigated 812 consecutive patients (median age, 83 years; 57% women), including 316 with 50% ≤ LVEF <60% and 496 with 60% ≤ LVEF, and compared the clinical backgrounds of the 2 groups and their prognoses for cardiac mortality or HF readmission. Two hundred four adverse outcomes occurred at a median of 366 days. Multivariable Cox regression tests adjusted for age, sex, heart rate, atrial fibrillation, estimated glomerular filtration rate, N‐terminal pro‐B‐type natriuretic peptide, and prior heart failure hospitalization revealed that systolic blood pressure (hazard ratio [HR], 0.925 [95% CI, 0.862–0.992];
P
=0.028), high‐density lipoprotein to C‐reactive protein ratio (HR, 0.975 [95% CI, 0.944–0.995];
P
=0.007), and left ventricular end‐diastolic volume index (HR, 0.870 [95% CI, 0.759–0.997];
P
=0.037) were uniquely associated with outcomes among patients with 50% ≤ LVEF <60%, whereas only the ratio of peak early mitral inflow velocity to velocity of mitral annulus early diastolic motion e′(HR, 1.034 [95% CI, 1.003–1.062];
P
=0.034) was associated with outcomes among patients with 60% ≤ LVEF.

Conclusions
Prognostic factors show distinct differences between patients with HFpEF with 50% ≤ LVEF <60% and with 60% ≤ LVEF. These findings suggest that the 2 groups have different inherent pathophysiology.

Registration

URL:
https://upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000024414
; Unique identifier: UMIN000021831 PURSUIT‐HFpEF.
Endothelial Foxp1 Regulates Neointimal Hyperplasia Via Matrix Metalloproteinase‐9/Cyclin Dependent Kinase Inhibitor 1B Signal Pathway
Authors: Chen Xiaoli , Xu Jianfei , Bao Wenzhen , Li Hongda , Wu Wenrun , Liu Jiwen , Pi Jingjiang , Tomlinson Brian , Chan Paul , Ruan Chengchao , Zhang Qi , Zhang Lin , Fan Huimin , Morrisey Edward , Liu Zhongmin , Zhang Yuzhen , Lin Li , Liu Jie , Zhuang Tao 
Published: July 2022

Background
The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. Endothelial Foxp1 (forkhead box P1) has been shown to control endothelial cell (EC) proliferation and migration in vitro. However, whether EC‐Foxp1 participates in neointimal formation in vivo is not clear. Our study aimed to investigate the roles and mechanisms of EC‐Foxp1 in neointimal hyperplasia.

Methods and Results
The wire injury femoral artery neointimal hyperplasia model was performed in Foxp1 EC‐specific loss‐of‐function and gain‐of‐function mice. EC‐Foxp1 deletion mice displayed the increased neointimal formation through elevation of vascular smooth muscle cell proliferation and migration, and the reduction of EC proliferation hence reendothelialization after injury. In contrast, EC‐Foxp1 overexpression inhibited the neointimal formation. EC‐Foxp1 paracrine regulated vascular smooth muscle cell proliferation and migration via targeting matrix metalloproteinase‐9. Also, EC‐Foxp1 deletion impaired EC repair through reduction of EC proliferation via increasing cyclin dependent kinase inhibitor 1B expression. Delivery of cyclin dependent kinase inhibitor 1B‐siRNA to ECs using RGD (Arg‐Gly‐Asp)‐peptide magnetic nanoparticle normalized the EC‐Foxp1 deletion‐mediated impaired EC repair and attenuated the neointimal formation. EC‐Foxp1 regulates matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B signaling pathway to control injury induced neointimal formation.

Conclusions
Our study reveals that targeting EC‐Foxp1‐matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B pathway might provide future novel therapeutic interventions for restenosis.
Basque Food
Authors: Goirizelaia Maialen , Iturregui Leire , Unda Annette 
Published: July 2022

Abstract
This study looks at Basque migrants in the United States and shows how different geographical locations there attracted different groups of migrants over time and how the immigrants organised themselves as a diaspora community and maintained their identity. Emigration from the Basque Country to the United States began during the Gold Rush in 1848; since then there have been multiple, distinct waves of immigration. The study’s results are based on in-depth interviews with Basque Americans and a survey. We analysed Basque communities in the Far West, New England, the Mid-Atlantic states, North Carolina and Florida, and found that Basque food is the most common factor by which Basque migrants maintain their identity, regardless of state, place or generation. Even so, there are differences among communities, which distinguish them from each other. Consequently, in order to connect with the diaspora and create diaspora strategies, governments should take these differences into account.
The Arabs and the Muslims
Authors: Alrmizan Mohammed 
Published: July 2022

Abstract
Both Arab and Muslim migrants have noticeable populations in all parts of the world. This article qualitatively investigates the Arabs, the Muslims, and mainly diaspora and transnationalism theories from historical and social understandings, based on primary and secondary sources. It engages conceptually in defining Arabs and Muslims through the lenses of diaspora and transnationalism theories, discusses theoretical issues and explores the status of the Arab and the Muslim diaspora(s) and transnational communities through primary data and the findings of the Global Muslim Diaspora Project, which surveyed 7,147 participants between 2018 and 2019. The report shows that the Arab experience abroad might be best described as diaspora, whereas Muslim migrants would be best referred to as transnational communities. Diaspora and transnationalism theories, among others, and particularly migration theories, must not be used interchangeably; each term should be used carefully to avoid confusion, especially when Arabs and Muslims are being studied.
Establishing a Digital Belonging
Authors: Madenoglu Dila Naz 
Published: July 2022

Abstract
A sense of belonging is one of the most important human needs. Immigrants might experience this differently because they tend to feel a lack of belonging to their host or home country. Nowadays, however, social media allows immigrants and diasporic groups to establish a digital sense of belonging. Members of the Turkish diaspora in Germany are inclined to use social media, especially Facebook, as a platform to connect with their roots, be informed about Turkish news, prove their Turkishness, and provide solidarity for each other. For this paper, we interviewed fifteen Turkish-Germans to get some insight into their perceptions about developing a digital belonging to Turkey through Facebook. We used discourse analysis to analyse their statements. The results suggest that Facebook allows Turkish-Germans to develop a digital belonging to Turkey through its specific features; however, it decreases their sense of belonging to Germany, as stated in the interviews.