bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing the time‐to‐freezing for clinical apheresis plasma meets quality specifications
Authors: Winter Kelly M. , Webb Rachel G. , Mazur Eugenia , Ismay Sue , Marinakis Dimitra , Marks Denese C. 
Published: September 2023

AbstractBackground and ObjectivesIn Australia, the vast distances between blood collection centres and processing facilities make it challenging to align supply with demand. Increasing the time to freezing for clinical plasma beyond 6 h would alleviate supply issues. This study aimed to determine the quality of clinical apheresis plasma frozen within 12 h of collection.Materials and MethodsApheresis plasma (n = 20) collected at donor centres was immediately transported to a blood processing facility, stored at 26°C and sampled aseptically at 6, 8 and 12 h post collection. Frozen samples were thawed, and coagulation factors (F) II, V, VII, VIII and XIII, von Willebrand factor (vWF) and fibrinogen were measured using a coagulation analyser.ResultsFVIII concentrations declined in plasma frozen at 6, 8 and 12 h post collection (1.22 ± 0.27, 1.21 ± 0.25 and 1.16 ± 0.24 IU/mL, respectively) but not significantly (p = 0.3338). Importantly, all components met the FVIII specification (>0.7 IU/mL) for clinical plasma. Fibrinogen concentrations were stable from 6 to 12 h (p = 0.3100), as were vWF concentrations (p = 0.1281). Coagulation factors II, V, VII and XIII were not significantly different (p > 0.05 for all factors).ConclusionClinical apheresis plasma can be frozen within 12 h of collection, allowing collections from donor centres further from processing centres and increasing supply.
An Improved Static Model for Bidirectional Notched Continuum Robot Considering the Cable Tension Loss
Authors: Wang Zhengyu , Jia Zirui , Qian Sen , Wang Daoming , Yu Xiang , Liu Xuchang 
Published: September 2023

Abstract
The notched continuum mechanism is particularly suitable for natural orifice transluminal surgery benefiting from its small size and hollow structure. However, the widely used kinematic model based on constant curvature assumption does not reveal the actual deformation of the continuum mechanism, and its control accuracy is unstable, while the general mechanics model has the problem that the tension of the distal driving cable is difficult to measure. In this paper, a nonconstant curvature static model for a bidirectional V-shaped notched continuum mechanism is presented. The deformation of each part of the continuum mechanism from the distal end to the proximal end is analyzed in turn. The tension loss of the driving cable caused by the contact with the continuum mechanism is modeled using the capstan equation. The recursive equation between the deformation of each part of the continuum mechanism from the proximal end is derived, which can be solved numerically. The bending state of the continuum mechanism can then be estimated when only the tension of the proximal flexible cable is known. The model is experimentally verified by driving the continuum mechanism to move at a very low speed. The experiment results show that the estimation effect of the proposed model is significantly improved compared with that of the constant curvature model.
Design and Implementation of Upper-Body Exoskeleton for Assistance of Individuals With Manual Handling Tasks
Authors: Chen Bing , Ni Xiang , Zi Bin , Xu Qingsong , Qian Jun 
Published: September 2023

AbstractThis paper illustrates the design and testing of an upper-body exoskeleton for the assistance of individuals with load-lifting and load-carrying tasks, and the provided assistive force can well match with the force required by the human. First, the biomechanics of the human lumbar during the squat lifting of an object is described. Next, the modeling of the exoskeleton is introduced. Additionally, the hardware design of the exoskeleton is presented. The exoskeleton is mainly composed of a back-assist mechanism and an upper extremity labor-saving mechanism, which can assist the wearer’s lumbar during the squat lifting of an object and assist the wearer’s arms to carry an object during walking, respectively. Finally, experiments are conducted to evaluate the performance of the developed upper-body exoskeleton. The experimental results demonstrate that the exoskeleton has the potential to provide assistance for individuals with manual handling tasks. An average assistive force of 44.8 N can be provided for the wearer to lift a 10-kg object. During the squat lifting of the 10-kg object, reductions of 31.86% and 28.30% of the average muscle activities of the wearer’s lumbar erector spinae and thoracic erector spinae are observed, respectively. In addition, a reduction of 23.78% of the average muscle activity of the wearer’s biceps brachii is observed during walking while carrying the 10-kg object.
Hypothetical Interventions on Diet Quality and Lifestyle Factors to Improve Breast Cancer Survival: The Pathways Study
Authors: Ergas Isaac J. , Bradshaw Patrick T. , Cespedes Feliciano Elizabeth M. , Roh Janise M. , Kwan Marilyn L. , Laraia Barbara , Madsen Kristine A. , Yao Song , Thomsen Catherine , Kushi Lawrence H. 
Published: September 2023

Abstract

Background:
The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited.

Methods:
This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated.

Results:
Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82–0.94; RRextreme = 0.44, 95% CI: 0.26–0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85–0.96; RRextreme = 0.62, 95% CI: 0.43–0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84–0.95; RRextreme = 0.51, 95% CI: 0.33–0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced.

Conclusions:
Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors.

Impact:
We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.
Suppression of Tumor Cell Lactate-generating Signaling Pathways Eradicates Murine PTEN/p53-deficient Aggressive-variant Prostate Cancer via Macrophage Phagocytosis
Authors: Chaudagar Kiranj , Hieromnimon Hanna M. , Kelley Anne , Labadie Brian , Shafran Jordan , Rameshbabu Srikrishnan , Drovetsky Catherine , Bynoe Kaela , Solanki Ani , Markiewicz Erica , Fan Xiaobing , Loda Massimo , Patnaik Akash 
Published: September 2023

Abstract

Purpose:
Phosphatase and tensin homolog (PTEN) loss-of-function/PI3K pathway hyperactivation is associated with poor therapeutic outcomes and immune checkpoint inhibitor resistance across multiple malignancies. Our prior studies in Pb-Cre;PTENfl/flTrp53fl/fl genetically engineered mice (GEM) with aggressive-variant prostate cancer (AVPC) demonstrated tumor growth control in 60% mice following androgen deprivation therapy/PI3K inhibitor (PI3Ki)/programmed cell death protein 1 (PD-1) antibody combination, via abrogating lactate cross-talk between cancer cells and tumor-associated macrophages (TAM), and suppression of histone lactylation (H3K18lac)/phagocytic activation within TAM. Here, we targeted immunometabolic mechanism(s) of PI3Ki resistance, with the goal of durable tumor control in AVPC.

Experimental Design:
Pb-Cre;PTENfl/flTrp53fl/fl GEM were treated with PI3Ki (copanlisib), MEK inhibitor (trametinib) or Porcupine inhibitor (LGK'974) singly or their combinations. MRI was used to monitor tumor kinetics and immune/proteomic profiling/ex vivo coculture mechanistic studies were performed on GEM tumors or corresponding tumor-derived cell lines.

Results:
Given our proteomic profiling showing persistent MEK signaling within tumors of PI3Ki-resistant GEM, we tested whether addition of trametinib to copanlisib enhances tumor control in GEM, and we observed 80% overall response rate via additive suppression of lactate within TME and H3K18lac within TAM, relative to copanlisib (37.5%) monotherapy. The 20% resistant mice demonstrated feedback Wnt/β-catenin activation, resulting in restoration of lactate secretion by tumor cells and H3K18lac within TAM. Cotargeting Wnt/β-catenin signaling with LGK'974 in combination with PI3Ki/MEKi, demonstrated durable tumor control in 100% mice via H3K18lac suppression and complete TAM activation.

Conclusions:
Abrogation of lactate-mediated cross-talk between cancer cells and TAM results in durable ADT-independent tumor control in PTEN/p53-deficient AVPC, and warrants further investigation in clinical trials.
Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis
Authors: Pradhan Anjan K. , Modi Jinkal , Maji Santanu , Kumar Amit , Bhoopathi Praveen , Mannangatti Padmanabhan , Guo Chunqing , Afosah Daniel K. , Mochel Mark C. , Mukhopadhyay Nitai D. , Kirkwood John M. , Wang Xiang-Yang , Desai Umesh R. , Sarkar Devanand , Emdad Luni , Das Swadesh K. , Fisher Paul B. 
Published: September 2023

Abstract
Genome-wide gene expression analysis and animal modeling indicate that melanoma differentiation associated gene-9 (mda-9, Syntenin, Syndecan binding protein, referred to as MDA-9/Syntenin) positively regulates melanoma metastasis. The MDA-9/Syntenin protein contains two tandem PDZ domains serving as a nexus for interactions with multiple proteins that initiate transcription of metastasis-associated genes. Although targeting either PDZ domain abrogates signaling and prometastatic phenotypes, the integrity of both domains is critical for full biological function. Fragment-based drug discovery and NMR identified PDZ1i, an inhibitor of the PDZ1 domain that effectively blocks cancer invasion in vitro and in vivo in multiple experimental animal models. To maximize disruption of MDA-9/Syntenin signaling, an inhibitor has now been developed that simultaneously binds and blocks activity of both PDZ domains. PDZ1i was joined to the second PDZ binding peptide (TNYYFV) with a PEG linker, resulting in PDZ1i/2i (IVMT-Rx-3) that engages both PDZ domains of MDA-9/Syntenin. IVMT-Rx-3 blocks MDA-9/Syntenin interaction with Src, reduces NF-κB activation, and inhibits MMP-2/MMP-9 expression, culminating in repression of melanoma metastasis. The in vivo antimetastatic properties of IVMT-Rx-3 are enhanced when combined with an immune-checkpoint inhibitor. Collectively, our results support the feasibility of engineering MDA-9 dual-PDZ inhibitors with enhanced antimetastatic activities and applications of IVMT-Rx-3 for developing novel therapeutic strategies effectively targeting melanoma and in principle, a broad spectrum of human cancers that also overexpress MDA-9/Syntenin.
DNA Damage and Nuclear Morphological Changes in Cardiac Hypertrophy Are Mediated by SNRK Through Actin Depolymerization
Authors: Stanczyk Paulina J. , Tatekoshi Yuki , Shapiro Jason S. , Nayudu Krithika , Chen Yihan , Zilber Zachary , Schipma Matthew , De Jesus Adam , Mahmoodzadeh Amir , Akrami Ashley , Chang Hsiang-Chun , Ardehali Hossein 
Published: September 2023

BACKGROUND:
Proper nuclear organization is critical for cardiomyocyte function, because global structural remodeling of nuclear morphology and chromatin structure underpins the development and progression of cardiovascular disease. Previous reports have implicated a role for DNA damage in cardiac hypertrophy; however, the mechanism for this process is not well delineated. AMPK (AMP-activated protein kinase) family of proteins regulates metabolism and DNA damage response (DDR). Here, we examine whether a member of this family, SNRK (SNF1-related kinase), which plays a role in cardiac metabolism, is also involved in hypertrophic remodeling through changes in DDR and structural properties of the nucleus.

METHODS:

We subjected cardiac-specific
Snrk
–/–
mice to transaortic banding to assess the effect on cardiac function and DDR. In parallel, we modulated SNRK in vitro and assessed its effects on DDR and nuclear parameters. We also used phosphoproteomics to identify novel proteins that are phosphorylated by SNRK. Last, coimmunoprecipitation was used to verify Destrin (DSTN) as the binding partner of SNRK that modulates its effects on the nucleus and DDR.

RESULTS:

Cardiac-specific
Snrk
–/–
mice display worse cardiac function and cardiac hypertrophy in response to transaortic banding, and an increase in DDR marker pH2AX (phospho-histone 2AX) in their hearts. In addition, in vitro
Snrk
knockdown results in increased DNA damage and chromatin compaction, along with alterations in nuclear flatness and 3-dimensional volume. Phosphoproteomic studies identified a novel SNRK target, DSTN, a member of F-actin depolymerizing factor proteins that directly bind to and depolymerize F-actin. SNRK binds to DSTN, and DSTN downregulation reverses excess DNA damage and changes in nuclear parameters, in addition to cellular hypertrophy, with SNRK knockdown. We also demonstrate that SNRK knockdown promotes excessive actin depolymerization, measured by the increased ratio of G-actin to F-actin. Last, jasplakinolide, a pharmacological stabilizer of F-actin, rescues the increased DNA damage and aberrant nuclear morphology in SNRK-downregulated cells.

CONCLUSIONS:
These results indicate that SNRK is a key player in cardiac hypertrophy and DNA damage through its interaction with DSTN. This interaction fine-tunes actin polymerization to reduce DDR and maintain proper cardiomyocyte nuclear shape and morphology.
Sleeping Difficulties, Sleep Duration, and Risk of Hypertension in Women
Authors: Haghayegh Shahab , Strohmaier Susanne , Hamaya Rikuta , Eliassen A. Heather , Willett Walter C. , Rimm Eric B. , Schernhammer Eva S. 
Published: September 2023

BACKGROUND:
Rates of poor sleep and hypertension are alarming worldwide. In this study, we investigate the association between sleeping difficulties and sleep duration with hypertension risk in women.

METHODS:
Sixty-six thousand one hundred twenty-two participants of the Nurses’ Health Study 2, who were free of hypertension at baseline (2001), were followed prospectively for 16 years and incident hypertension assessed every 2 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hypertension incidence associated with sleeping difficulties and sleep duration.

RESULTS:

During follow-up, we documented 25 987 incident cases of hypertension. After controlling for demographic and lifestyle risk factors, compared with women who slept 7 to 8 hours, women with shorter sleep duration had a significantly higher risk of hypertension (≤5 hours: HR, 1.10 [95% CI, 1.05–1.16]; 6 hours: HR, 1.07 [95% CI, 1.03–1.10]), whereas the risk for women with longer sleep duration was not statistically significant (9 hours: HR, 1.03 [95% CI, 0.97–1.10]; >9 hours: HR, 1.08 [95% CI, 0.94–1.23]). Compared with women rarely having difficulty falling or staying asleep, women sometimes or usually having these sleep difficulties had significantly higher risk of developing hypertension (HR, 1.14 [95% CI, 1.11–1.17] and 1.28 [95% CI, 1.22–1.35];
P
trend
<0.001). Early morning awakening was not associated with hypertension risk (
P
trend
=0.722). There was no effect modification by night work or chronotype.

CONCLUSIONS:
Difficulty falling or staying asleep and short sleep duration were associated with higher risk of hypertension among women in our study. Screening for poor sleep could be useful in identifying people at higher risk for hypertension.
Repair of Aortic Regurgitation in Young Adults: Sooner Rather Than Later
Authors: Barradas‐Pires Ana , Merás Pablo , Constantine Andrew , Costola Giulia , de la Cal Teresa Segura , Rafiq Isma , Kempny Aleksander , Li Wei , Babu‐Narayan Sonya V. , Hoschtitzky J. Andreas , Gatzoulis Michael A. , Rubio Antonio Martinez , Dimopoulos Konstantinos 
Published: September 2023

Background
Establishing surgical criteria for aortic valve replacement (AVR) in severe aortic regurgitation in young adults is challenging due to the lack of evidence‐based recommendations. We studied indications for AVR in young adults with severe aortic regurgitation and their outcomes, as well as the relationship between presurgical echocardiographic parameters and postoperative left ventricular (LV) size, function, clinical events, and valve‐related complications.

Methods and Results

Data were collected retrospectively on 172 consecutive adult patients who underwent AVR or repair for severe aortic regurgitation between 2005 and 2019 in a tertiary cardiac center (age at surgery 29 [22–41] years, 81% male). One‐third underwent surgery before meeting guideline indications. Postsurgery, 65% achieved LV size and function normalization. LV ejection fraction showed no significant change from baseline. A higher presurgical LV end‐systolic diameter correlated with a lack of LV normalization (odds ratio per 1‐cm increase 2.81,
P
<0.01). The baseline LV end‐systolic diameter cut‐off for predicting lack of LV normalization was 43 mm. Pre‐ and postoperative LV dimensions and postoperative LV ejection fraction predicted clinical events during follow‐up. Prosthetic valve‐related complications occurred in 20.3% during an average 5.6‐year follow‐up. Freedom from aortic reintervention was 98%, 96.5%, and 85.4% at 1, 5, and 10 years, respectively.

Conclusions
Young adult patients with increased baseline LV end‐systolic diameter or prior cardiac surgery are less likely to achieve LV normalization after AVR. Clinicians should carefully balance the long‐term benefits of AVR against procedural risks and future interventions, especially in younger patients. Evidence‐based criteria for AVR in severe aortic regurgitation in young adults are crucial to improve outcomes.
The Effect of Mindfulness Practice on Adolescents: A Pilot Study
Authors: Goyal Pragati , Chandra Mina , Rushi  , Choudhary Mona 
Published: September 2023

Background: Adolescents experience various emotional, cognitive, and behavioral issues for which there is emerging evidence for mindfulness-based interventions, but these have not been investigated with Indian adolescents. Objectives: To study the impact of mindfulness practices on attention, perceived stress, emotional competence, and mental health among high school adolescents. Method: A single group theme-based 4-week (12 sessions) mindfulness intervention program was conducted on school-going adolescents with a pre-post scale-based assessment design. Results: Thirty-nine out of 45 recruited participants (mean age 15.9 ± 0.56 years; M:F = 2:1) completed the study with high session attendance rates (82.05%–100%). On a paired t-test, there was a significant improvement on the Digit Letter Substitution Test ( p < .001), the Perceived Stress Scale ( p < .001), and three subscales of the Emotional Competencies Scale-Revised ( p < .001–.004). Analysis of non-normal data on the Wilcoxon sign-ranked test revealed significant improvement in the Adequate Depth of Feeling subscale of Emotional Competence ( p < .001) and all subscales of the Strengths and Difficulties Questionnaire-Teacher Version ( p < .001–.048) Conclusion: The results indicate that formal mindfulness-based practices for adolescents have significant psychological benefits. Further randomized controlled effectiveness trials are required to establish effectiveness in the non-clinical adolescent population.
Barriers and Facilitators Related to Nasal Injury Among Preterm Neonates in Selected Neonatal Units of a Tertiary Care Centre, North India
Authors: Sandhu Monica , Kaur Rupinder , Kalyan Geetanjli , Kumar Praveen 
Published: September 2023

Introduction Preterm neonates require Non-invasive Respiratory Support (NiRS) because of underdeveloped lungs to administer pressurized oxygen for a long duration. The interface used to deliver NiRS can cause pressure injury at the nasal surface, septum, and bridge. Preterm neonates are more vulnerable to such injuries due to immature skin and septum. It is the responsibility of Health Care Professionals (HCPs) to prevent nasal injury through the implementation of evidence-based practices and innovative techniques to secure nasal interfaces. Objectives (1) To find out the barriers and facilitators related to nasal injury among preterm neonates in selected neonatal units of a Tertiary Care Centre, in North India. (2) To seek the remedial measures suggested by HCPs to prevent nasal injury. Methodology After obtaining permission from the head of the department of neonatology, covert participatory observations related to existing practices were made using an observation checklist. Focused Group Discussions (FGDs) were conducted with HCPs (Nursing Officers-43 and Physicians-10) and audio-recorded. Out of the total of eight FGDs, three were conducted with physicians in a group of 2–4 members and the remaining five with nursing officers in a group of 8–9 members, each of 15–20 min duration. FGD guide was used as a tool to guide the discussion. The qualitative data were analyzed by using Van Manen’s approach. Result The barriers identified were related to supplies, staff, and administration. Supplies include limited hospital supply of RAM cannula, reuse of hard ethylene oxide sterilized RAM cannula, lack of adequate size head caps; staff includes lack of awareness regarding the implications and effect of nasal injury among healthcare professionals, variable documentation of nasal injury; administration: no standard guidelines and lack of regular audits to prevent nasal injury. The facilitator suggested were motivated healthcare professionals. Suggested remedial measures were the availability of appropriate size RAM cannula, stockinette head caps, self-motivation, frequent inspection and early identification of nasal injury, staff education, and standard protocol of measures for nasal injury prevention. Conclusion There are concrete barriers and limited facilitators. There is a need to incorporate the suggested remedial measures to address barriers to preventing nasal injury among preterm neonates.