bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant phytochrome interactions decode light and temperature signals
Authors: Yi Chengwei , Gerken Uwe , Tang Kun , Philipp Michael , Zurbriggen Matias D , Köhler Jürgen , Möglich Andreas 
Published: September 2024

Abstract
Plant phytochromes perceive red and far-red light to elicit adaptations to the changing environment. Downstream physiological responses revolve around red-light-induced interactions with phytochrome-interacting factors (PIFs). Phytochromes double as thermoreceptors, owing to the pronounced temperature dependence of thermal reversion from the light-adapted Pfr to the dark-adapted Pr state. Here, we assess whether thermoreception may extend to the phytochrome:PIF interactions. While the association between Arabidopsis (Arabidopsis thaliana) PHYTOCHROME B (PhyB) and several PHYTOCHROME-INTERACTING FACTOR (PIF) variants moderately accelerates with temperature, the dissociation does more so, thus causing net destabilization of the phytochrome:PIF complex. Markedly different temperature profiles of PIF3 and PIF6 might underlie stratified temperature responses in plants. Accidentally, we identify a photoreception mechanism under strong continuous light, where the extent of phytochrome:PIF complexation decreases with red-light intensity rather than increases. Mathematical modeling rationalizes this attenuation mechanism and ties it to rapid red-light-driven Pr⇄Pfr interconversion and complex dissociation out of Pr. Varying phytochrome abundance, e.g. during diurnal and developmental cycles, and interaction dynamics, e.g. across different PIFs, modify the nature and extent of attenuation, thus permitting light-response profiles more malleable than possible for the phytochrome Pr⇄Pfr interconversion alone. Our data and analyses reveal a photoreception mechanism with implications for plant physiology, optogenetics, and biotechnological applications.
Tradable Risk Factors for Institutional and Retail Investors
Authors: Johansson Andreas , Sabbatucci Riccardo , Tamoni Andrea 
Published: September 2024

Abstract
We construct tradable risk factors using combinations of large and liquid mutual funds (long leg) and ETFs (exchange-traded funds) (long and short legs), based on their holdings, for both retail and institutional investors. Exploiting a novel dataset, our tradable factors take into account ETF shorting costs. Assessing the performance of our tradable factors against standard “on-paper” factors, we uncover an implementation shortfall of 2–4 percent annually. Shorting fees and transaction costs contribute to 58 percent of the performance differential between tradable and “on-paper” factors, assigning a non-trivial role to the opportunity cost of not trading the exact “on-paper” portfolio.
Demographic characteristics and comorbidities of patients with narcolepsy: a propensity-matched cohort study
Authors: Lipford Melissa C , Ip Wui , Awasthi Samir , Moore J Layne , Tippmann-Peikert Maja , Asfahan Shahir , Kumar-M Praveen , Pal Singh Gajinder , Gudeman Jennifer 
Published: September 2024

Abstract

Study Objectives
Narcolepsy has a complex phenotype owing to differences in symptomatology, disease severity, and comorbidities. This is the first study to use aggregate electronic health record (EHR) data and natural language processing (NLP) algorithms to characterize the demographics and comorbidities of a large cohort of patients with narcolepsy.

Methods
First-time Mayo Clinic patients (2000–2020) who had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using an NLP algorithm) were identified. A control cohort was propensity matched for birth year, age at first institutional encounter, sex, race, ethnicity, number of diagnosis codes, and mortality. Common comorbidities were compared and ranked between cohorts.

Results
In the EHR database (N = 6 389 186 patients), 2057 patients with narcolepsy were identified (median age, 32 years; 59.6% female; 92.6% white; and 89.2% non-Hispanic) and propensity matched with a control cohort. Among the top 20 comorbidities occurring more frequently in the narcolepsy cohort compared with the control cohort (odds ratio [OR], 1.67–3.94; p &lt; .001]) were sleep disorders (restless legs syndrome, obstructive sleep apnea, and insomnia), mood disorders (depression, dysthymia, and anxiety), and pain disorders (chronic pain syndrome, migraine, fibromyalgia, carpal tunnel syndrome, and myalgia). Other comorbidities significantly associated with narcolepsy (OR, 1.33–1.95) were irritable bowel syndrome (p &lt; .001), asthma (p &lt; .001), cervical spondylosis (p &lt; .01), syncope (p &lt; .01), and hypothyroidism (p &lt; .05).

Conclusions
This propensity-matched cohort study demonstrates increased psychiatric, sleep, and pain disorders in patients living with narcolepsy and challenges beyond narcolepsy-specific symptoms in this population. Understanding common narcolepsy-associated comorbidities may assist in tailoring treatment modalities.
Decoded cardiopoietic cell secretome linkage to heart repair biosignature
Authors: Garmany Armin , Arrell D Kent , Yamada Satsuki , Jeon Ryounghoon , Behfar Atta , Park Sungjo , Terzic Andre 
Published: September 2024

Abstract
Cardiopoiesis-primed human stem cells exert sustained benefit in treating heart failure despite limited retention following myocardial delivery. To assess potential paracrine contribution, the secretome of cardiopoiesis conditioned versus naïve human mesenchymal stromal cells was decoded by directed proteomics augmented with machine learning and systems interrogation. Cardiopoiesis doubled cellular protein output generating a distinct secretome that segregated the conditioned state. Altering the expression of 1035 secreted proteins, cardiopoiesis reshaped the secretome across functional classes. The resolved differential cardiopoietic secretome was enriched in mesoderm development and cardiac progenitor signaling processes, yielding a cardiovasculogenic profile bolstered by upregulated cardiogenic proteins. In tandem, cardiopoiesis enhanced the secretion of immunomodulatory proteins associated with cytokine signaling, leukocyte migration, and chemotaxis. Network analysis integrated the differential secretome within an interactome of 1745 molecules featuring prioritized regenerative processes. Secretome contribution to the repair signature of cardiopoietic cell-treated infarcted hearts was assessed in a murine coronary ligation model. Intramyocardial delivery of cardiopoietic cells improved the performance of failing hearts, with undirected proteomics revealing 50 myocardial proteins responsive to cell therapy. Pathway analysis linked the secretome to cardiac proteome remodeling, pinpointing 17 cardiopoiesis-upregulated secretome proteins directly upstream of 44% of the cell therapy-responsive cardiac proteome. Knockout, in silico, of this 22-protein secretome-dependent myocardial ensemble eliminated indices of the repair signature. Accordingly, in vivo, cell therapy rendered the secretome-dependent myocardial proteome of an infarcted heart indiscernible from healthy counterparts. Thus, the secretagogue effect of cardiopoiesis transforms the human stem cell secretome, endows regenerative competency, and upregulates candidate paracrine effectors of cell therapy-mediated molecular restitution.
Vascular smooth muscle BK channels limit ouabain‐induced vasocontraction: Dual role of the Na/K‐ATPase as a hub for Src‐kinase and the Na/Ca‐exchanger
Authors: Orth Tobias , Pyanova Anastasia , Lux Simon , Kaiser Peter , Reinheimer Isabel , Nielsen Daniel Løgstrup , Khalid Josef Ali , Rognant Salomé , Jepps Thomas A. , Matchkov Vladimir V. , Schubert Rudolf 
Published: September 2024

AbstractLarge‐conductance, calcium‐activated potassium channels (BK channels) and the Na/K‐ATPase are expressed universally in vascular smooth muscle. The Na/K‐ATPase may act via changes in the intracellular Ca2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na/K‐ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain‐induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA‐2 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine‐induced contractions. The cardiotonic steroid, ouabain (10−5 M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro‐contractile effect of IBTX on methoxamine‐induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel‐mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co‐localization of the Na/K‐ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain‐induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain‐induced activation of the BK channel, act in an independent manner.
Non‐canonical RNA‐binding protein ANXA11 regulates microRNA resorting into small extracellular vesicles to mediate cisplatin resistance
Authors: Zhang Yifan , Huang Qiang , Shen Yujie , Ren Henglei , Wu Chunping , Zhou Liang 
Published: September 2024

AbstractThe sensitivity of laryngeal squamous cell carcinoma (LSCC) to chemotherapy shows large heterogeneity. The role of miRNA in small extracellular vesicles (sEV) in chemotherapy resistance is under investigation. However, the regulation and sorting mechanism of sEV miRNAs remains unclear. In this study, small RNA sequencing was used to explore miRNA expression profiles in sEV of LSCC after cisplatin stimulation; RNA pull‐down, mass spectrometry, and EMSA were used to clarify the binding of candidate RNA‐binding protein (RBP) and candidate miRNA. Immunostaining and microRNA fluorescence in situ hybridization were performed to identify how candidate RBP affects miRNA stability and nuclear/cytoplasmic distribution. In vivo experiments were performed to verify the biological functions and response to cisplatin of candidate RBP. We found that cisplatin stimulation induced increased expression of miR‐148a‐3p and sEV sorting. ANXA11 binds to miR‐148a‐3p in a sequence‐specific manner. ANXA11 inhibits tumor cell proliferation and drug resistance by binding to and retaining miR‐148a‐3p. Cisplatin stimulation reduced ANXA11 expression and promoted miR‐148a‐3p efflux through sEV pathways. ANXA11 overexpression reduced in vivo tumor proliferation and cisplatin‐resistance. Taken together, ANXA11 mediates cisplatin resistance through sEV miRNA resorting. Mechanically, ANXA11 binds to miR‐148a‐3p in a sequence‐specific manner to regulate its resorting and thus influences tumor proliferation and chemoresistance.
Navigating Spaces of Belonging: Undergraduate Nursing Students’ Experiences in Online Learning Environments
Authors: Montague Janet , Haghiri-Vijeh Roya , Tsui Joyce , Connell Michelle , Cosgrove Caitlin 
Published: September 2024

Abstract

AIM
The aim of the study was to explore undergraduate nursing students’ experiences of belonging while studying online during the COVID-19 pandemic.

BACKGROUND
The use of online learning platforms increased drastically during the pandemic. Limited research exists on nursing students’ experiences of belonging while studying online.

METHOD
An explanatory sequential mixed-methods design was used for this study. This article reports on phase two, the qualitative component, which employed interpretive description methodology to understand nursing students’ experiences.

RESULTS
Ten semistructured interviews were completed, and four themes were identified: factors contributing to students’ sense of belonging online, navigating the online learning environment, creating safe online spaces during times of uncertainty, and students’ vision of developing a sense of belonging online.

CONCLUSION
Fostering nursing students’ sense of belonging is critical to their retention, persistence, and overall academic success when learning online.
Engaging Interprofessional Health Students in a Prescription Produce Plan
Authors: Battle Kimberly , Falls Katherine H. , Waters Leland , Slattum Patricia W. , Parsons Pamela L. , Wendte Jered M. , Diallo Ana F. 
Published: September 2024

Abstract
Nursing students participated in an interprofessional student-led prescription produce program (PPP) serving low-income older adults attending a community-based wellness and care coordination program. Students engaged in an online training module covering nutrition education and health promotion, integral components of a PPP. Ninety-five percent of students self-rated themselves as somewhat confident/very confident to participate in the PPP after completing an online learning module. Further investigation is needed on integrating students from diverse health professions to address the multifaceted factors related to nutrition and other social determinants of health affecting the management of chronic diseases.
Diagnostic Accuracy of Lipase as Early Predictor of Postoperative Pancreatic Fistula: Results from the LIPADRAIN study
Authors: Doussot Béranger , Doussot Alexandre , Ayav Ahmet , Santucci Nicolas , Deguelte Sophie , Sow Amadou Khalilou , El Amrani Mehdi , Duvillard Laurence , Piessen Guillaume , Girard Edouard , Mabrut Jean-Yves , Garnier Jonathan , Ortega-Deballon Pablo , Fournel Isabelle , Facy Olivier 
Published: September 2024

Objective:
To evaluate the diagnostic accuracy of drain fluid lipase as an early predictor of postoperative pancreatic fistula and establish the most appropriate day for their measure.

Background:
Clinically relevant postoperative pancreatic fistula remains a potentially life-threatening complication after pancreatic surgery. Early detection strategies remain key to reduce both the incidence and the burden of pancreatic fistula.

Methods:
The LIPAse DRAIN (LIPADRAIN) study is a multicenter, prospective diagnostic study conducted in 7 tertiary university hospitals. Drain fluid values to detect clinically relevant postoperative pancreatic fistula from postoperative day 1 to postoperative day 6 were evaluated using receiver operating characteristic curve analysis. A biomarker was considered to be relevant for clinical use if its area under the curve (AUC) was greater than 0.75.

Results:
Of the 625 patients included in the analysis, clinically relevant postoperative pancreatic fistula occurred in 203 (32%) patients. On postoperative days 3 and 4, drain fluid lipase was a reliable biomarker to detect clinically relevant postoperative pancreatic fistula (AUC: 0.761; 95% confidence interval [CI]: 0.761–0.799 and AUC: 0.784; 95% CI: 0.743–0.821, respectively). On postoperative day 3, with a threshold of 299 units/L, drain fluid lipase yielded a negative predictive value of 51%, sensitivity of 78%, and specificity of 63% for the detection of clinically relevant postoperative pancreatic fistula.

Conclusions:
In this multicenter prospective study, drain fluid lipase is a reliable biomarker at postoperative days 3 and 4 for the diagnosis of clinically relevant postoperative pancreatic fistula after pancreatic surgery and should be systematically measured on postoperative day 3.
Reliability of a Photo-Based Modified Foot Posture Index (MFPI) in Quantifying Severity of Foot Deformity in Children With Cerebral Palsy
Authors: Georgiadis Andrew G. , Davids Jon R. , Goodbody Christine M. , Howard Jason J. , Karamitopoulos Mara S. , Payares-Lizano Monica , Pierz Kristan A. , Rhodes Jason T. , Shore Benjamin J. , Shrader M. Wade , Tabaie Sean A. , Thompson Rachel Mednick , Torres-Izquierdo Beltran , Wimberly Robert Lane , Hosseinzadeh Pooya ,   Research in Neuromuscular Orthopaedics (RINO) Study Group
Published: September 2024

Introduction:
Children with cerebral palsy (CP) have high rates of foot deformity. Accurate assessment of foot morphology is crucial for therapeutic planning and outcome evaluation. This study aims to evaluate the reliability of a novel photo-based Modified Foot Posture Index (MFPI) in the evaluation of foot deformity in children with CP.

Methods:
Thirteen orthopaedic surgeons with neuromuscular clinical focus from 12 institutions evaluated standardized standing foot photographs of 20 children with CP, scoring foot morphology using the MFPI. Raters scored the standardized photographs based on five standard parameters. Two parameters assessed the hindfoot: curvature above and below the malleoli and calcaneal inversion/eversion. Three parameters assessed the midfoot and forefoot: talonavicular congruence, medial arch height, and forefoot abduction/adduction. Summary MFPI scores range from −10 to +10, where positive numbers connote planovalgus, whereas negative numbers connote a tendency toward cavovarus. Intra- and interrater reliability were calculated using a 2-way mixed model of the intraclass correlation coefficient (ICC) set to absolute agreement.

Results:
Feet spanned the spectrum of potential pathology assessable by the MFPI, including no deformity, mild, moderate, and severe planovalgus or cavovarus deformities. All scored variables showed high intrarater reliability with ICCs from 0.891 to 1. ICCs for interrater reliability ranged from 0.965 to 0.984. Hindfoot total score had an ICC of 0.979, with a 95% CI, 0.968-0.988 (P<0.001). The forefoot total score had an ICC of 0.984 (95% CI, 0.976-0.991, P<0.001). Mean total score by the MFPI was 3.67 with an ICC of 0.982 (95% CI, 0.972-0.990, P<0.001).

Conclusions:
The photo-based MFPI demonstrates high intra- and interrater reliability in assessing foot deformities in children with CP. Its noninvasive nature and ease of use make it a promising tool for both clinical and research settings. MFPI should be considered as part of standard outcomes scores in studies regarding the treatment of CP-associated foot deformities.

Level of Evidence:
Level V.
Central Venous Oxygen Saturation for Estimating Mixed Venous Oxygen Saturation and Cardiac Index in the ICU: A Systematic Review and Meta-Analysis
Authors: Motazedian Pouya , Beauregard Nickolas , Letourneau Isabelle , Olaye Ida , Syed Sarah , Lam Eric , Di Santo Pietro , Mathew Rebecca , Clark Edward G. , Sood Manish M. , Lalu Manoj M. , Hibbert Benjamin , Bugeja Ann 
Published: September 2024

OBJECTIVES:
The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo
2) in estimating mixed venous oxygen saturation (Svo
2) and cardiac index in critically ill patients.

DATA SOURCES:
A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024.

STUDY SELECTION:
Studies of patients in the ICU for whom Scvo
2 and at least one reference standard test was performed (thermodilution and/or Svo
2) were included.

DATA EXTRACTION:
Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo
2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments.

DATA SYNTHESIS:
Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo
2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo
2 was 0.83 (95% CI, 0.75–0.89) with a mean difference of 2.98% toward Scvo
2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46–0.48; p < 0.0001).

CONCLUSIONS:
There is moderate reliability for Scvo
2 in predicting Svo
2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo
2 in predicting cardiac index.
Meta-analysis of Targeted Therapies in EGFR-mutated Non–Small Cell Lung Cancer
Authors: Qureshi Zaheer , Altaf Faryal , Jamil Abdur , Siddique Rimsha 
Published: September 2024

Background:
Some of the non–small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib.

Methods:
A systematic electronic search was conducted on 3 electronic databases—Scopus, PubMed, and Web of Science—from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis.

Results:
Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]).

Conclusions:
The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.