bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of video analysis and expert modelling for technique development in novice sport climbers: A randomized controlled study
Authors: Blagus Rok , Leskošek Bojan , Okršlar Luka , Vreček Nace , Debevec Tadej
Published: February 2023

Sport climbing is a multifaceted sport that also requires appropriate techniques to optimize movements. As augmented feedback is known to facilitate motor learning, we investigated the utility of adding video analysis and expert modelling to standardized verbal feedback for the acquisition of three climbing-specific techniques (drop knee, heel hook and high step). Twenty-six novice climbers (12 women) completed two testing sessions before and after a training intervention that consisted of three coached climbing sessions targeting the three techniques. Participants were randomly assigned to a control group, which solely received standardized verbal feedback or an experimental group that additionally received standardized video analysis and expert modelling using the Dartfish tablet application. Video recordings were subsequently evaluated by two climbing experts on a 7-point scale. The expert scores were higher in the experimental than in the control group for the high step (causal total effect (CTE) 0.38, 95% confidence interval (CI) [0.06, 0.68]). Improvements for the drop knee (CTE = 0.12, 95% CI [−0.24, 0.48]) and heel hook (CTE = −0.05, 95% CI [−0.42, 0.31]) were similar in both groups. For the drop knee, we, however, observed a positive causal direct effect (CDE = 0.38, 95% CI [0.07, 0.68]), which was comparable to that observed for the high step but also a negative causal mediator effect via the perceived difficulty (CME = −0.26, 95% CI [−0.51, −0.04]). Compared to verbal feedback solely, the addition of video analysis and expert modelling might facilitate the acquisition of certain climbing techniques, such as high step, in novice climbers.
Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer
Authors: Paluch-Shimon Shani , Neven Patrick , Huober Jens , Cicin Irfan , Goetz Matthew P. , Shimizu Chikako , Huang Chiun-Sheng , Lueck Hans Joachim , Beith Jane , Tokunaga Eriko , Contreras Jessica Reyes , de Sant’Ana Rosane Oliveira , Wei Ran , Shahir Ashwin , Nabinger Sarah C. , Forrester Tammy , Johnston Stephen R. D. , Harbeck Nadia
Published: February 2023

Background:

Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2− tumors may have different tumor biology and treatment response compared to postmenopausal patients.

Objectives:

We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2− EBC in monarchE.

Design:

Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated.

Methods:

Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician’s choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months).

Results:

Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population.

Conclusion:

Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.
Synthesis, Molecular Docking, and Cytotoxic Evaluation of Fluorinated Podophyllotoxin Derivatives
Authors: Thanh Nguyen Ha , Bao Le Quang , Pham-The Hai , Anh Dang Thi Tuyet , Van Kiem Phan
Published: February 2023

Objective: The study was conducted to evaluate the in vitro and in silico anticancer activity of fluorinated podophyllotoxin derivatives. Methods: Microwave-assisted multicomponent reactions were carried out in an Anton Paar Microwave Synthetic Reactor Monowave 400 in order to synthesize fluorinated podophyllotoxin derivatives. These products were identified by spectral analysis and evaluated for their cytotoxicity against 4 types of human cancer cell lines (KB, HepG2, A549, and MCF7), as well as human embryonic kidney (Hek) 293 cells using MTT protocol. Molecular docking was conducted using 2 crystal structures of tubulin—colchicine (PDB ID: 4O2B) and topoisomerase II—etoposide (PDB ID: 3QX3) complexes. Results: Two potent cytotoxic fluorinated podophyllotoxin–naphthoquinone compounds were synthesized in good yields. They displayed high cytotoxic activity against all the tested cell lines, with IC50 values ranging from 0.58 to 3.17 µM. Notably, product 8a showed low toxicity against the Hek-293 cell line. Molecular docking results showed that products 8a and 8b participated in the same key interactions provided by etoposide with both topoisomerase and DNA chain domains. The binding energy values calculated for 8a and 8b are acceptable. Conclusion: This study revealed that products 8a and 8b exhibited promising in vitro and in silico anticancer activity and could be recognized as promising anticancer agents.
Springing in Your “Cleanup” Journey
Authors: Caldwell Sheila
Published: February 2023

Now, more than ever, nurses need to focus on self-care. This is especially true of school nurses returning to all regular responsibilities while managing multiple outbreaks of respiratory illnesses this past winter. In this brief article, the author discusses the various meanings of the word “clean-up” and how they can be applied to improved self-care.
Treatment de-escalation in Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia: the emerging role of chemotherapy-free regimens
Authors: Haddad Fadi G. , Sawyers Jacki , Short Nicholas J.
Published: February 2023

The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many to re-evaluate the role of allogeneic SCT for patients who achieve CMR with potent TKI regimens. Recently, the chemotherapy-free combinations of blinatumomab plus TKIs were shown to be safe and effective in newly diagnosed Ph-positive ALL, sparing patients the toxicities associated with intensive chemotherapy. In particular, encouraging early results have been seen with the combination of blinatumomab plus ponatinib, suggesting that this regimen may represent a chemotherapy-free and SCT-sparing strategy for patients with Ph-positive ALL. Herein, we discuss the current evidence for frontline therapies of Ph-positive ALL, the treatment de-escalation strategies over time, and the role of allogeneic SCT in view of the emergence of newer chemotherapy-free regimens using potent TKIs.
A Bibliometric and Visual Analysis of the Most Cited Articles on Disc Arthroplasty
Authors: De Stefano Frank A. , Warner Tyler , Reardon Taylor , Jarrah Ryan , Mayo Timothy , Ezeudu Chibueze S. , Fiani Brian
Published: February 2023

Study Design

Bibliometric literature review.

Objective

Total disc arthroplasty (TDA) is an evolving technique used by surgeons to preserve neural elements and range of motion in patients with degenerative disc disease, spondylosis and more. In comparison to discectomy, disc arthroplasty has been shown to decrease morbidity, reduce adjacent-level disease, and preserve pre-operative range of motion. The objective of this manuscript is to provide a bibliometric analysis of the use of disc arthroplasty in scientific literature and highlight the main contributing authors and their publication characteristics.

Methods

The Scopus database was used to perform a title-specific, keyword-based search for all publications until June 2022. The keyword “total disc arthroplasty” was used. The most-cited 100 articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty first author, institution, country of origin, publishing journal, Source Normalized, Impact Per Paper (SNIP), and Hirsch index.

Results

Our search on disc arthroplasty yielded 580 articles that were published, with the first publication on the topic found in 1966. The most cited 100 articles received a total of 8694 citations, with an average of 86.94 citations per article. After assessing countries with the greatest contributions, United States, China, and Germany were top 3 with 54, 14, and 7 articles, respectively.

Conclusion

The bibliometric analysis provides an overview of how medical research is analyzed in academic medicine. In the present study, we evaluated the global trends in disc arthroplasty for the treatment of degenerative disc disease.
Initial Heart Rate Predicts Functional Independence in Patients With Spinal Cord Injury Requiring Surgery: A Registry-Based Study in a Mature Trauma System Over the Past 10 Years
Authors: Mouchtouris Nikolaos , Luck Trevor , Yudkoff Clifford , Hines Kevin , Franco Daniel , Al Saiegh Fadi , Thalheimer Sara , Khanna Omaditya , Prasad Srinivas , Heller Joshua , Harrop James , Jallo Jack
Published: February 2023

Study Design

Retrospective Cohort Study.

Objectives

To determine the ability of early vital sign abnormalities to predict functional independence in patients with SCI that required surgery.

Methods

A retrospective analysis of data extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients >18 years with a diagnosis of SCI who required urgent spine surgery in Pennsylvania from 1/1/2010-12/31/2020 and had complete records available.

Results

A total of 644 patients met the inclusion criteria. The mean age was 47.1 ± 14.9 years old and the mean injury severity score (ISS) was 22.3 ± 12.7 with the SCI occurring in the cervical, thoracic, and lumbar spine in 61.8%, 19.6% and 18.0%, respectively. Multivariable logistic regression analyses for predictors of functional independence at discharge showed that higher HR at the scene (OR 1.016, 95% CI 1.006-1.027, P = .002) and lower ISS score (OR .894, 95% CI .870-.920, P < .001) were significant predictors of functional independence. Similarly, higher admission HR (OR 1.015, 95% CI 1.004-1.027, P = .008) and lower ISS score (OR .880, 95% CI 0.864-.914, P < .001) were significant predictors of functional independence. Peak Youden indices showed that patients with HR at scene >70 and admission HR ≥83 were more likely to achieve functional independence.

Conclusions

Early heart rate is a strong predictor of functional independence in patients with SCI. HR at scene >70 and admission HR ≥83 is associated with improved outcomes, suggesting lack of neurogenic shock.
Simultaneous Arthroscopic Glenohumeral Stabilization and Glenoid Microfracture in Young, Active-Duty Military Patients: Outcomes at 5-Year Follow-up
Authors: Green Clare K. , Scanaliato John P. , Sandler Alexis B. , Dunn John C. , Covillon Emma , Parnes Nata
Published: February 2023

Background:

Glenohumeral instability represents a common cause of shoulder pain and disability among active-duty members of the military and is associated with the development of glenoid osteochondral defects.

Purpose:

To report clinical outcomes and survivorship after combined microfracture of isolated chondral lesions of the glenoid and labral repair among young, active-duty military patients and to compare outcomes with those of patients who underwent isolated shoulder stabilization.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Included were 31 active-duty military patients aged <40 years who underwent simultaneous microfracture of chondral lesions of the glenoid and labral repair for shoulder instability between January 2011 and January 2017 (microfracture group) and 209 patients without chondral defects who underwent shoulder stabilization during the same time period (instability group). Preoperative and 5-year postoperative outcomes (range of motion [ROM], visual analog scale [VAS] for pain, Single Assessment Numeric Evaluation [SANE] score, American Shoulder and Elbow Surgeons [ASES] shoulder score, and Rowe instability score) were compared within and between groups, and separate subgroup analyses were performed to determine whether variant of instability and dominant-shoulder involvement were associated with worse outcomes.

Results:

The mean follow-up was significantly longer for the microfracture group versus the instability group (95.58 ± 23.12 vs 83.38 ± 25.93 months; P = .014). Age and sex distributions were similar between groups. In both groups, there was significant pre- to postoperative improvement on all outcomes scores ( P = .0001 for all). When compared with the instability cohort, microfracture patients had significantly worse postoperative VAS pain (2.65 ± 1.78 vs 1.55 ± 1.92; P = .003), SANE (79.13 ± 14.43 vs 91.23 ± 13.20; P < .0001), and ASES (79.90 ± 13.87 vs 89.03 ± 14.28; P = .001) scores, as well as decreased ROM in forward flexion (151.29° ± 11.76° vs 155.48° ± 10.3°; P = .039) and external rotation (63.65° ± 8.34° vs 65.17° ± 0.64°; P = .010). At latest follow-up, 58% of microfracture patients had returned to active-duty military service compared with 93.78% of isolated instability patients ( P < .0001).

Conclusion:

Combined microfracture and arthroscopic labral repair produced modest, albeit statistically significant, improvements in patient-reported outcome measures and may be a reasonable treatment option for patients with chondral lesions who are not candidates for arthroplasty. However, microfracture patients had significantly worse outcomes than patients who underwent stabilization without concomitant chondral defects.
Evidence for Utilization of Injectable Biologic Augmentation in Primary Rotator Cuff Repair: A Systematic Review of Data From 2010 to 2022
Authors: Bono Olivia J. , Jenkin Bryan , Forlizzi Julianne , Mousad Albert , Le Breton Stephen , MacAskill Meghan , Mandalia Krishna , Mithoefer Kai , Ramappa Arun , Ross Glen , Shah Sarav S.
Published: February 2023

Background:

Biologic healing after rotator cuff repair remains a significant challenge. Injectable biologic augmentation may improve tissue quality at the suture-tendon interface.

Purpose:

To investigate the effect of injectable biologic supplementation in rotator cuff repair and to assess the quality and adherence to evolving reporting standards.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were 40 studies: 29 preclinical (in vivo animal models) and 11 clinical. Each clinical study was assessed for quality, risk of bias, and adherence to relevant MIBO (Minimum Information for Studies Evaluating Biologics in Orthopaedics) guidelines. The outcomes of interest were reported load to failure, load to gap, gap size, and stiffness in the preclinical studies, and healing rate and any patient-reported outcome measures in the clinical studies.

Results:

Injectables reported included growth factors (eg, transforming growth factor–beta 3, erythropoietin), bone marrow–derived mesenchymal stem cells and adipose-derived mesenchymal stem cells (ADSCs), and other agents such as platelet-rich plasma (PRP) and hyaluronic acid. The most common findings for preclinical injectables were increased load to failure (16/29 studies; 55.2%) and improved collagen histological quality (11/29 studies; 37.9%). All 11 clinical studies (10 PRP, 1 ADSC) indicated no adverse events, with similar or improved patient-reported outcomes compared with repairs in the control groups. In 1 study utilizing an innovative delivery technique, a concentrated PRP globule with fibrin matrix was shuttled over a suture to maintain concentrated PRP at the repair site and demonstrated a significant decrease in retears ( P = .03) at a 31-month follow-up. A matched-cohort study investigating augmentation with ADSCs demonstrated a significantly lower retear rate in the ADSC-augmented group than the control group at a 28-month follow-up ( P < .001). On average, the clinical studies adhered to 66% of relevant MIBO reporting guidelines and had a low risk of bias.

Conclusion:

Approximately 83% of preclinical studies found a positive biomechanical or histological effect, with no studies showing an overall negative effect. Clinically, utilization of innovative delivery techniques may reduce the risk of arthroscopic washout of PRP and improve retear rates. ADSCs were shown to reduce retear rates at a 28-month follow-up.
A Case of ALG6-CDG with Explosive Onset of Intractable Epilepsy During Infancy
Authors: Clark Daniel James , Murray Thomas , Drees Michael , Kulkarni Neil
Published: February 2023

ALG6-CDG is a rare, but second most common, type 1 congenital disorder of glycosylation (CDG) caused by a defect in the α-1-3-glucosyltransferase (ALG6) enzyme in the N-glycan assembly pathway. Many mutations have been identified and inherited in an autosomal recessive pattern. There are less than 100 ALG6-CDG cases reported, all sharing the phenotype of hypotonia and developmental delay. The majority (perhaps >70%) have seizures, but a minority have intractable epilepsy or epileptic encephalopathy. We report the clinical course, EEG findings, and neuroimaging of a child found to have compound heterozygous alleles c.257 + 5G > A and c.680G > A (p.G227E) who developed explosive onset of intractable epilepsy and epileptic encephalopathy. Initially, CDG was not suspected due to its rarity and lack of multi-organ system involvement, but rapid whole exam sequence (8-day turnaround) revealed the specific diagnosis quickly.
Determinants of Consumers’ Decision to Switch to Islamic Banking System: A Case Study of Oman
Authors: Faiza Kiran
Published: February 2023

Islamic banking is becoming a major alternative to conventional banking in many parts of the world, including the Gulf region. Although one of the prevalent reasons includes religious inclination, the variety of products added by Islamic banks contributes to customers switching from conventional to Islamic banking. This study analyses the factors responsible for customers’ decision to switch to Islamic banking in Oman through a questionnaire survey from Omani nationals in Muscat, Salalah, and Sohar. The data analysis tool included Structural Equation Modelling (SEM) analysis using SPSS and AMOS software. Some of the variables incorporated in the study include physical quality, outcome quality, interaction quality, customer satisfaction, trust, price, religion, and social prestige, which are the dependent variables. The independent variable includes the decision to switch. These variables have been incorporated to evaluate their impact on customers’ decision-making to switch from conventional to Islamic banking. The results indicate that interaction quality significantly influences the switching decision, whereas physical environment and outcome quality could not influence the decision. Moreover, customer satisfaction and trust positively affect the decision. Religion significantly influences switching decisions, while the price and social prestige have no association with it. The findings suggest that religion is a strong determinant and positively impacts switching decisions. Additionally, the people of Oman consider the quality of service, customer service, and trust before switching decisions.
Buoyancy-driven flow of magnetohydrodynamic hybrid nanofluids in an open cavity with permeable horizontal walls
Authors: Chandra Roy Nepal , Monira Sherajum , Subba Reddy Gorla Rama
Published: February 2023

The buoyancy-driven flow of hybrid nanofluids in an open cavity is examined in the presence of a magnetic field with an angle to the horizontal axis. The right end of the cavity is open, and the left wall is supposed to be heated. Moreover, the horizontal walls are deemed to be permeable and maintained at ambient temperature. The successive over-relaxation (SOR) technique is applied with the finite-difference method to solve the dimensionless equations. A comparison is executed with formerly published results which provide a good agreement. The grid refinement test has also been carried out to increase the accuracy. Flow and temperature profiles are investigated for the Rayleigh number ( Ra = 104, 105, 106), Reynolds number (Re = 5, 8, 10, 20, 100), Hartmann number ( Ha = 0, 5, 10), concentration of nanoparticles ( φ1 or φ2 = 0.0, 0.05, 0.1), angle of inclination of the magnetic field ( γ = 0°, 30°, 45°), aspect ratio ( A = 1, 2, 3, 4), and suction/blow parameter ( S = −1, 0, 1). Results have been elucidated based on streamlines, isotherms, local Nusselt number ( Nu), and average Nusselt number ( Nuavg). It is noted that the changes in the variables significantly affect streamlines and isotherms. The heat transfer for Cu-Fe3O4/water hybrid nanofluid is higher about 9.98% compared to Fe3O4/water nanofluid and 26.41% compared to water. Furthermore, all other parameters noticeably augment both Nu and Nuavg.
The Carbon Footprint of the Craniomaxillofacial Surgeon: A Single Center Analysis of 3D-Printed Constructs
Authors: Heron Matthew J. , Bhagwat Atharva M. , Zhu Katherine J. , Yusuf Cynthia T. , Febre-Alemañy David A. , Lopez Christopher D. , Yang Robin
Published: February 2023

Introduction:

Three-dimensional (3D) printing plays an expansive role in craniofacial surgical planning and implementation. To better understand when the benefits of this technology outweigh its environmental costs, a focused exploration of the environmental impact of 3D printing is warranted to quantify carbon emissions attributable to craniofacial surgical constructs.

Methods:

All invoice data from commercial vendors used at Johns Hopkins Hospital for the 2-year period from January 2020 to December 2021 were reviewed. Information on the material composition of each construct was recorded. Additionally, a total of 19 commercial printers were included. Conversion factors from the U.S. EIA were used to calculate the carbon emissions generated by the fuel consumption of each printer per hour.

Results:

Invoice data revealed 406 patient-specific constructs (158 contour models, 104 guides, 84 implants, and 60 splints). A total of 2644.4 printer hours and 36.1 MW of power were needed to manufacture all constructs. This is equivalent to releasing 15.71 metric tons of carbon emissions, corresponding to the emissions produced by burning 7882.1 kg of coal or 36.4 barrels of oil.

Conclusion:

3D printing is a resource-intensive practice in CMF surgery. Therefore, when weighing patient benefits against environmental detriment, CMF surgeons must determine indications where 3D printing is unessential. Restricting prints to the anatomy of interest, minimizing support structures, and reusing printed constructs may all help to lessen the environmental impact of this growing practice.
Oscar Wilde, Dener Pamplona de Abreu: Approaches of DIY by the use of clothes, appearances, and photographs
Authors: Bonadio Maria Claudia
Published: February 2023

In this article, I observe how the writer Oscar Wilde and the luxury couturier Dener Pamplona de Abreu used clothes, appearances, and photographs to create disruptive images in terms of fashion and masculinity in the different contexts in which they lived, using for this, both do-it-yourself (DIY) approaches and especially bricolage. I also note the importance of photography in the transmission of images and for the constitution of the image of Wilde as an esthete and Dener as a luxury couturier, also highlighting how such appearance and behaviors contributed to the understanding of both as deviant from the norm, generating punishments. In addition, I address the importance of the DIY culture in the history of gay fashion and culture.
Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A
Authors: Gonzalez-Menendez Pedro , Phadke Ira , Olive Meagan E , Joly Axel , Papoin Julien , Yan Hongxia , Galtier Jérémy , Platon Jessica , Kang Sun Woo Sophie , McGraw Kathy L. , Daumur Marie , Pouzolles Marie , Kondo Taisuke , Boireau Stéphanie , Paul Franciane , Young David J , Lamure Sylvain , Mirmira Raghavendra G , Narla Anu , Cartron Guillaume , Dunbar Cynthia E. , Boyer-Clavel Myriam , Porat-Shliom Natalie , Dardalhon Valerie , Zimmermann Valerie S , Sitbon Marc , Dever Thomas , Mohandas Narla , Da Costa Lydie M , Udeshi Namrata D. , Blanc Lionel , Kinet Sandrina , Taylor Naomi
Published: February 2023

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate, but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. Here, we show that SLC7A1/CAT1-dependent arginine uptake and its catabolism to the polyamine spermidine control human erythroid specification of HSPCs via activation of the eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on its hypusination, a post-translational modification resulting from the conjugation of the aminobutyl moiety of spermidine to lysine. Notably, attenuation of hypusine synthesis in erythroid progenitors--by inhibition of deoxyhypusine synthase--abrogates erythropoiesis but not myeloid cell differentiation. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A and accordingly, progenitors with decreased hypusine activity exhibit diminished oxidative phosphorylation. This impacted pathway is critical for eIF5A-regulated erythropoiesis as interventions augmenting mitochondrial function partially rescue human erythropoiesis under conditions of attenuated hypusination. Levels of mitochondrial ribosomal proteins were especially sensitive to the loss of hypusine and we find that the ineffective erythropoiesis linked to haploinsufficiency of RPS14 in del(5q) myelodysplastic syndrome is associated with a diminished pool of hypusinated eIF5A. Moreover, patients with RPL11-haploinsufficient Diamond-Blackfan anemia as well as CD34+ progenitors with downregulated RPL11 exhibit a markedly decreased hypusination in erythroid progenitors, concomitant with a loss of mitochondrial metabolism. Thus, eIF5A-dependent protein synthesis regulates human erythropoiesis and our data reveal a novel role for RPs in controlling eIF5A hypusination in HSPC, synchronizing mitochondrial metabolism with erythroid differentiation.
Selective modulation of activated protein C activities by a nonactive site–targeting nanobody library
Authors: Sim Derek S. , Shukla Meenal , Mallari Cornell R. , Fernández José A. , Xu Xiao , Schneider Doug , Bauzon Maxine , Hermiston Terry W. , Mosnier Laurent O.
Published: February 2023

Activated protein C (APC) is a pleiotropic coagulation protease with anticoagulant, anti-inflammatory, and cytoprotective activities. Selective modulation of these APC activities contributes to our understanding of the regulation of these physiological mechanisms and permits the development of therapeutics for the pathologies associated with these pathways. An antibody library targeting the nonactive site of APC was generated using llama antibodies (nanobodies). Twenty-one nanobodies were identified that selectively recognize APC compared with the protein C zymogen. Overall, 3 clusters of nanobodies were identified based on the competition for APC in biolayer interferometry studies. APC functional assays for anticoagulant activity, histone H3 cleavage, and protease-activated receptor 1 (PAR1) cleavage were used to understand their diversity. These functional assays revealed 13 novel nanobody-induced APC activity profiles via the selective modulation of APC pleiotropic activities, with the potential to regulate specific mechanisms for therapeutic purposes. Within these, 3 nanobodies (LP2, LP8, and LP17) inhibited all 3 APC functions. Four nanobodies (LP1, LP5, LP16, and LP20) inhibited only 2 of the 3 functions. Monofunction inhibition specific to APC anticoagulation activity was observed only by 2 nanobodies (LP9 and LP11). LP11 was also found to shift the ratio of APC cleavage of PAR1 at R46 relative to R41, which results in APC-mediated biased PAR1 signaling and APC cytoprotective effects. Thus, LP11 has an activity profile that could potentially promote hemostasis and cytoprotection in bleedings associated with hemophilia or coagulopathy by selectively modulating APC anticoagulation and PAR1 cleavage profile.
Conifers and non-native tree species shift trophic niches of generalist arthropod predators in Central European beech forests
Authors: Wildermuth Benjamin , Fardiansah Riko , Matevski Dragan , Lu Jing-Zhong , Kriegel Peter , Scheu Stefan , Schuldt Andreas
Published: February 2023

Background

Functional diversity is vital for forest ecosystem resilience in times of climate-induced forest diebacks. Admixing drought resistant non-native Douglas fir, as a partial replacement of climate-sensitive Norway spruce, to native beech forests in Europe appears promising for forest management, but possible consequences for associated biota and ecosystem functioning are poorly understood. To better link forest management and functional diversity of associated biota, we investigated the trophic niches (∆13C, ∆15N) of epigeic generalist predators (spiders and ground beetles) in mixed and pure stands of European beech, Norway spruce and non-native Douglas fir in north-west Germany. We assessed the multidimensional niche structure of arthropod predator communities using community-based isotopic metrics.

Results

Whilst arthropod ∆13C differed most between beech (high ∆13C) and coniferous stands (low ∆13C), ∆15N was lowest in non-native Douglas fir. Tree mixtures mitigated these effects. Further, conifers increased isotopic ranges and isotopic richness, which is linked to higher canopy openness and herb complexity. Isotopic divergence of ground beetles decreased with Douglas fir presence, and isotopic evenness of spiders in Douglas fir stands was lower in loamy sites with higher precipitation than in sandy, drier sites.

Conclusions

We conclude that tree species and particularly non-native trees alter the trophic niche structure of generalist arthropod predators. Resource use and feeding niche breadth in non-native Douglas fir and native spruce differed significantly from native beech, with more decomposer-fueled and narrower feeding niches in beech stands (∆13C, isotopic ranges and richness). Arthropod predators in non-native Douglas fir, however, had shorter (∆15N) and simplified (isotopic divergence) food chains compared to native forest stands; especially under beneficial abiotic conditions (isotopic evenness). These findings indicate potential adverse effects of Douglas fir on functional diversity of generalist arthropod predators. As tree mixtures mitigated differences between beech and conifers, mixed stands including (non-native) conifers constitute a promising compromise between economic and conservational interests.
Gut microbiome variations in Rhinopithecus roxellanae caused by changes in the environment
Authors: Zhao Gang , Qi Mingpu , Wang Qiankun , Hu Changmin , Li Xiang , Chen Yingyu , Yang Jingyuan , Yu Huiliang , Chen Huanchun , Guo Aizhen
Published: February 2023

Background

The snub-nosed monkey (Rhinopithecus roxellanae) is an endangered animal species mainly distributed in China and needs to be protected. Gut microbiome is an important determinant of animal health and population survival as it affects the adaptation of the animals to different foods and environments under kinetic changes of intrinsic and extrinsic factors. Therefore, this study aimed to elucidate gut fecal microbiome profiles of snub-nosed monkeys affected by several extrinsic and intrinsic factors, including raising patterns (captive vs. wild), age, sex, and diarrheal status to provide a reference for making protection strategies.

Results

The 16S rRNA gene sequencing was firstly used to pre-check clustering of 38 fecal samples from the monkeys including 30 wild and 8 captive (5 healthy and 3 diarrheal) from three Regions of Shennongjia Nature Reserve, Hubei Province, China. Then the 24 samples with high-quality DNA from 18 wild and 6 captive (4 healthy and 2 diarrheal) monkeys were subjected to shotgun metagenomic sequencing to characterize bacterial gut microbial communities. We discovered that the raising pattern (captive and wild) rather than age and sex was the predominant factor attributed to gut microbiome structure and proportionality. Wild monkeys had significantly higher bacterial diversity and lowerBacteroidetes/Firmicutesratios than captive animals. Moreover, the gut microbiomes in wild healthy monkeys were enriched for the genes involved in fatty acid production, while in captive animals, genes were enriched for vitamin biosynthesis and metabolism and amino acid biosynthesis from carbohydrate intermediates. Additionally, a total of 37 antibiotic resistant genes (ARG) types were detected. Unlike the microbiome diversity, the captive monkeys have a higher diversity of ARG than the wild animals.

Conclusion

Taken together, we highlight the importance of self-reprogramed metabolism in the snub-nosed monkey gut microbiome to help captive and wild monkeys adapt to different intrinsic and extrinsic environmental change.
Use of clinical scores in young Australian adults for prediction of atherosclerosis in middle age
Authors: Huynh Quan , Venn Alison J. , Magnussen Costan G. , Yang Hong , Venkataraman Prasanna , Dwyer Terence , Marwick Thomas H.
Published: February 2023

We sought to apply a simple cardiovascular health tool not requiring laboratory tests (the Fuster-BEWAT score, FBS) to predict subclinical atherosclerosis. This study included 2657 young adults (< 40 years of age). In the prognostic group (n = 894, followed for 13 years until aged 40–50 years at follow-up), the primary outcome was presence of carotid plaque measured by carotid ultrasound at follow-up. Of these 894 participants, 86 (9.6%) had unilateral, and 23 participants (2.6%) had bilateral, carotid plaques at follow-up. The baseline FBS was predictive of carotid plaque at follow-up [odds ratio OR = 0.86 (95% CI 0.77–0.96) per 1-SD increase in FBS], similar to prediction from Pooled Cohort Equation [PCE, OR = 0.72 (0.61–0.85) per 1-SD decrease in PCE]. Risk scores at baseline predicted outcomes more strongly than those at follow-up, and did so independently of any changes over 13 years of follow-up. Similar discrimination for predicting carotid plaque after 13 years was found for both baseline FBS [C-statistic = 0.68 (95% CI 0.62–0.74)] and PCE [C-statistic = 0.69 (95% CI 0.63–0.75)]. Application of this FBS prognostic information to a contemporary cohort of 1763 young adults anticipates the future development of plaque in 305 (17.3%), especially in the 1494 participants (85%) with ≤ 2 metrics of ideal health. In conclusions, FBS measured in young adulthood predicted atherosclerosis 13 years later in middle age, independent of score changes over the follow-up period, emphasizing the importance of early damage to vascular health. FBS may be a simple and feasible risk score for engaging low-risk young people with reduction of future cardiovascular risk.
Association between red blood cell distribution width-to-albumin ratio and prognosis of patients with acute myocardial infarction
Authors: Li Hongwu , Xu Yinjun
Published: February 2023

Background

Red blood cell distribution width (RDW) and albumin level were considered to be related to the prognosis of patients with acute myocardial infarction (AMI). This study aims to investigate the correlation between RAR and 90-day mortality in AMI patients.

Methods

Data of AMI patients were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III) database. According to the median, RAR < 4.32 was regarded as low RAR level group, and RAR ≥ 4.32 as high RAR level group; low RDW level group was defined as < 14.00%, and high RDW level group as ≥ 14.00%; albumin < 3.30 g/dL was low level group, and albumin ≥ 3.30 g/dL as high level group. The outcome was the mortality rate within 90 days after admission to ICU. Univariate and multivariate Cox models were performed to determine the relationship between RAR and 90-day mortality in AMI patients with hazard ratio (HR) and 95% confidence interval (CI). Stratification analyses were conducted to explore the effect of RAR on 90-day mortality in different subgroups of age, gender, simplified acute physiology score II (SAPS II), elixhauser comorbidity index (ECI) score, treatment modalities and white blood cell.

Results

Of the total 2081 AMI patients, 543 (26.09%) died within 90-day follow-up duration. The results showed that high RAR (HR = 1.65, 95% CI 1.34–2.03) and high RDW levels (HR = 1.31, 95% CI 1.08–1.61) were associated with an increased risk of death in AMI patients, and that high albumin level was related to a decreased risk of death (HR = 0.77, 95%CI 0.64–0.93). The relationship of RAR level and the mortality of AMI patients was also observed in the subgroup analysis. Additionally, the finding indicated that RAR might be a more effective biomarker for predicting 90-day mortality of AMI patients than albumin, RDW.

Conclusion

RAR may be a potential marker for the prognostic assessment of AMI, and a high RAR level was correlated with increased risk of 90-day mortality of AMI patients.
Accumulation of blood chromium and cobalt in the participants with metal objects: findings from the 2015 to 2018 National Health and Nutrition Examination Survey (NHANES)
Authors: He Jinshen , Li Jinfei , Wu Song , Wang Jiaoju , Tang Qi
Published: February 2023

Background

Chromium (Cr) and cobalt (Co) are the essential elements for producing metal implants, but might have potential health issues. The research on the correlation between metal implants and blood Cr and Co on a large population is still limited.

Methods

National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health status of Americans began in the early 1960s. The study was based on the NHANES database from two data collection years (2015–2016 and 2017–2018). The exposure variable of this study was whether the participants had metal objects in the body or not. The outcome variables were blood concentrations of Cr and Co. Age, body mass index, sex, race/ethnicity, income to poverty ratio, tap water behavior, shellfish/fish/tuna/salmon eating habits, level of education, smoking behavior, marital status, blood hemoglobin, and data collection years were included as confounding variables.

Results

A total of 4412 participants, aged 40 years or older, were included in this analysis, consisting of the without metal objects group (n = 3150) and the metal objects group (n = 1262). Metal objects was positively correlated to the accumulation of blood Cr (β = 0.072, 95% CI: 0.043–0.102, p < 0.001) and blood Co (β = 0.079, 95% CI: 0.049–0.109, p < 0.001). However, the positive correlation of metal objects with blood Cr was only presented in women (β = 0.112, 95% CI: 0.074–0.151, p < 0.001), but not in men. Meanwhile, the positive relationship between metal objects and blood Cr/Co was not observed in the Asian subgroup.

Conclusions

Blood Cr and Co concentrations were statistically higher in people with metal objects, but with race and sex differences.

Level of Evidence

Level IV, cross-sectional study
Psychosocial changes during COVID-19 lockdown on nursing home residents, their relatives and clinical staff: a prospective observational study
Authors: Oliveira Adriana Catarina De Souza , Gallego María Gómez , Martínez Carmelo Gómez , Martínez Elena Carrasco , Molina Jorge Moreno , Morante Juan José Hernández , Pérez Paloma Echevarría
Published: February 2023

Background

Previous works have observed an increase of depression and other psychological disorders on nursing home residents as a consequence of coronavirus disease 2019 (COVID-19) lockdown; however, there are few studies that have performed a comprehensive evaluation of all people involved in nursing homes environment. The objective of the work was to analyse the impact of lockdown on psychosocial factors of nursing home residents, relatives and clinical staff and how these variables have influenced residents’ survival.

Methods

A prospective study was designed. Evaluations were performed at three different times: a) at the beginning of Spanish confinement, in March 2020; b) just before the second wave of the pandemic, with relaxation of security measures but in lockdown, and c) in January–February 2021, at the end of the second wave, when visits were already allowed. The study was conducted on three different nursing homes. Three hundred and one residents, 119 clinical staff and 51 relatives took part in the study. Anxiety and depression were evaluated in all participants. A scale on the meaning of suffering was also performed. In addition, burnout status was also determined in the clinical staff.

Results

All participants showed lower depression during lockdown, while at the beginning and at the end of the confinement, these values were significantly increased. In residents, these changes were dependent of cognitive status (p = 0.012). Anxiety was significantly higher in residents. The evolution of anxiety was similar than with depression, with lower values during confinement, although clinical staff showed higher anxiety levels at the beginning. The feeling of suffering was significantly lower in the clinical staff than in resident and relative groups. Residents’ survival was dependent of cognitive status (p = 0.018) and voluntary confinement (p < 0.001).

Conclusions

During the first COVID-19 lockdown, psychological wellbeing of residents cared in nursing homes, their relatives and staff did not seem to be seriously affected. Previous mental health in relatives and staff together with a resilient approach to the adversity might partly be protecting factors. The lack of consequences on residents’ anxiety, depression and perception of social support may reflect the special attention and care they received. Finally, as in the current study only data of the first two COVID-19 waves were analysed, its findings might be partly generalized to all the pandemic.
Exploring the osteoporosis treatment gap after fragility hip fracture at a Tertiary University Medical Center in Thailand
Authors: Mahaisavariya Chantas , Vanitcharoenkul Ekasame , Kitcharanant Nitchanant , Chotiyarnwong Pojchong , Unnanuntana Aasis
Published: February 2023

Background

(1) To evaluate the prescription rate of anti-osteoporosis medication, and (2) to identify factors associated with patients not receiving anti-osteoporosis medication or, when prescribed, not persisting with medication 1 year after hip fracture treatment.

Methods

We retrospectively reviewed the medical records of all fragility hip fracture patients admitted to the orthopedic unit of the Faculty of Medicine Siriraj Hospital, Mahidol University, between July 1, 2016, and December 31, 2019. We identified patients who did not receive anti-osteoporosis medication both 6 months and 1 year after fracture treatment. Patients who did not receive the medication 1 year after their treatment were enrolled and interviewed using a no-treatment questionnaire.

Results

In total, 530 patients with fragility hip fractures were eligible (mean age, 79.0 years), and most (74.5%) were women. Only 148 patients (31.6%) received anti-osteoporosis medication 1 year after hip fracture. Logistic regression analysis identified predictors for not receiving the medication: male sex (OR 1.8; 95% CI 1.1–3.0), Charlson comorbidity index score ≥ 5 (OR 1.5; 95% CI 1.0–2.3), and secondary school education or below (OR 2.0; 95% CI 1.2–3.3). The main reason for not receiving the medication was that healthcare providers neither discussed nor initiated pharmacological treatment for osteoporosis (48.2%). When the medication was prescribed, non-persistence primarily stemmed from transportation difficulties that resulted in patients missing follow-ups (50.0%).

Conclusions

Improved physician attitudes toward anti-osteoporosis medications might enhance the treatment rate. Developing a follow-up team and facilitating access to medications (eg, courier delivery to patients) would promote therapy compliance.

Trial registrations

The protocol for the first phase and second phase was approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021) and for the second phase, patients-informed consent forms used in the cross-sectional component were approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021). The research was registered with the Thai Clinical Trials Registry (TCTR number: 20210824002). The study was conducted in accordance with the Declaration of Helsinki. Each patient (or a relative/caregiver) provided informed consent in writing or by telephone to participate in this second study phase.