bluuebunny/crossref_metadata_2025 huggingface dataset:
New directions in cancer and aging: State of the science and recommendations to improve the quality of evidence on the intersection of aging with cancer control
Authors: Kobayashi Lindsay C. , Westrick Ashly C. , Doshi Aalap , Ellis Katrina R. , Jones Carly R. , LaPensee Elizabeth , Mondul Alison M. , Mullins Megan A. , Wallner Lauren P.
Published: February 2022

Background

The global population of older cancer survivors is growing. However, the intersections of aging‐related health risks across the cancer control continuum are poorly understood, limiting the integration of aging into cancer control research and practice. The objective of this study was to review the state of science and provide future directions to improve the quality of evidence in 6 priority research areas in cancer and aging.

Methods

The authors identified priority research areas in cancer and aging through an evidence‐based Research Jam process involving 32 investigators and trainees from multiple disciplines and research centers in aging and cancer; then, they conducted a narrative review of the state of the science and future directions to improve the quality of evidence in these research areas. Priority research areas were defined as those in which gaps in scientific evidence or clinical practice limit the health and well‐being of older adults with cancer.

Results

Six priority research areas were identified: cognitive and physical functional outcomes of older cancer survivors, sampling issues in studies of older cancer survivors, risk and resilience across the lifespan, caregiver support and well‐being, quality of care for older patients with cancer, and health disparities. Evidence in these areas could be improved through the incorporation of bias reduction techniques into longitudinal studies of older cancer survivors, novel data linkage, and improved representation of older adults in cancer research.

Conclusions

The priority research areas and methodologies identified here may be used to guide interdisciplinary research and improve the quality of evidence on cancer and aging.
A multicenter, open‐label, single‐arm study of anamorelin (ONO‐7643) in patients with cancer cachexia and low body mass index
Authors: Naito Tateaki , Uchino Junji , Kojima Toru , Matano Yutaka , Minato Koichi , Tanaka Kentaro , Mizukami Takuro , Atagi Shinji , Higashiguchi Takashi , Muro Kei , Takayama Koichi , Furuse Junji , Morishima Eiichiro , Takiguchi Toru , Tamura Kazuo
Published: February 2022

Background

Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).

Methods

This multicenter, open‐label, single‐arm study enrolled Japanese patients with non–small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m2, involuntary weight loss > 2% in the last 6 months, and anorexia). Patients were administered 100 mg of anamorelin once daily for up to 24 weeks. The primary end point was a composite clinical response (CCR) at 9 weeks, which was defined as an increase in body weight of ≥5% from the baseline, an increase of ≥2 points in the score of the 5‐item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Therapy, and being alive.

Results

One hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/m2, respectively. The CCR rate at 9 weeks was 25.9% (95% confidence interval [CI], 18.3%‐35.3%), which met the primary end point with a lower 95% CI exceeding the prespecified minimum of 8%. Improvements in body weight and anorexia were durable and were accompanied by improvements in patients' global impression of change for appetite/eating‐related symptoms and overall condition. Adverse drug reactions occurred in 37 of 101 treated patients (36.6%), with the most common being glycosylated hemoglobin increases, constipation, and peripheral edema.

Conclusions

Anamorelin improved body weight and anorexia‐related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.

Lay Summary

Anamorelin is a drug that stimulates appetite and promotes weight gain.

This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss.

Anamorelin was found to improve body weight and anorexia‐related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated.

These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.
The prognostic significance of further genotyping H3G34 diffuse hemispheric gliomas
Authors: Vuong Huy Gia , Le Hieu Trong , Dunn Ian F.
Published: February 2022

Background

H3G34‐mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends.

Methods

Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34‐mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan‐Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed.

Results

In total, 20 studies with 257 H3G34‐mutant DHGs were included for integrated analyses. The H3 glycine‐to‐valine (H3G34V) mutation showed a significantly worse prognosis than the glycine‐to‐arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208‐7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes.

Conclusions

The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.
Triptycene‐Based Molecular Rods for Langmuir‐Blodgett Monolayers
Authors: Kaletová Eva , Santos Hurtado Carina , Císařová Ivana , Teat Simon J. , Kaleta Jiří
Published: February 2022

Herein we introduce fully modular synthesis leading to three representative examples of rigid molecular rods that are intended to form sturdy monolayers on various surfaces. These molecules contain two triptycene units that are designed to interlock into a compact “double‐decker” structure. Two of the three final products provided suitable crystals for X‐ray diffraction (analyzed on synchrotron), allowing deeper insight into packing in the 3‐D crystal lattice. The acidity of all three compounds were determined by capillary electrophoresis, and the pKa values ranged between 2.06‐2.53. All three rigid rods easily formed Langmuir‐Blodgett monolayers (LBMs) on the water‐air interfaces, with the area per molecule equal to 55–59 Å2/molecule, suggesting tight intermolecular packing. The thickness of all three films reached ∼19 Å after transfer to a gold (111) surface, meaning that individual molecules are tilted maximally 38° from the axis perpendicular to the surface. The structure of one of these films on a gold (111) surface was visualized by AFM. These geometrically unique molecules represent promising platforms with a wide scope of applicability in the supramolecular architecture.
Identification of potential biomarkers in urine and plasma after consumption of tobacco product in horses
Authors: Ishii Hideaki , Leung Gary Ngai‐Wa , Yamashita Shozo , Nagata Shun‐ichi , Kushiro Asuka , Sakai Satoshi , Toju Kota , Okada Jun , Kawasaki Kazumi , Kusano Kanichi , Kijima‐Suda Isao
Published: February 2022

The use of nicotine stimulants in horses is generally banned in horse racing and equestrian sports—accidental consumption of tobacco products is one of the possible causes of nicotine exposure in horses. The authors recently reported a comprehensive metabolic study of nicotine in equines, differentiating between nicotine exposure and sample contamination by means of a nicotine biomarker trans‐3′‐hydroxycotinine. To identify potential biomarkers for the differentiation of genuine nicotine administration and consumption of tobacco products, tobacco leaves (equivalent to 250 mg of nicotine) were nasoesophageally administered to three thoroughbred mares. Quantification methods of anatabine in plasma and urine were newly developed and validated and successfully applied to postadministration samples. Previously reported simultaneous quantification methods of eight target analytes including nicotine and its metabolites in plasma and urine were also applied to the samples. The results demonstrate that both trans‐3′‐hydroxycotinine and anatabine could be used as potential biomarkers in equine urine and plasma to indicate recent exposure to tobacco products in horses. As well, trans‐3′‐hydroxycotinine had the longest half‐life as a detectable metabolite in urine and plasma. To our knowledge, this is the first report of a comprehensive study of tobacco product detection in horses.
Short‐term temporal variation of coastal marine eDNA
Authors: Jensen Mads Reinholdt , Sigsgaard Eva Egelyng , Ávila Marcelo de Paula , Agersnap Sune , Brenner‐Larsen William , Sengupta Mita Eva , Xing Yingchun , Krag Marcus Anders , Knudsen Steen Wilhelm , Carl Henrik , Møller Peter Rask , Thomsen Philip Francis
Published: February 2022

Temporal variation in eDNA signals is increasingly explored for understanding community ecology in aquatic habitats. Seasonal changes have been addressed using eDNA sampling, but very little is known regarding short‐term temporal variation that spans hours to days. To address this, we filtered marine water samples from a single coastal site in Denmark every hour for 32 h. We used metabarcoding to target both fish and broader eukaryote diversity and evaluated temporal changes in this marine community. Results revealed variation in fish species richness (15–27) and eukaryote class richness (35–64) across the 32 h of sampling, and we further evaluated sampling efforts needed to reach different levels of diversity saturation. Relative read frequency data for both fish and eukaryotes indicated a clear diel change in community composition, with different communities detected during daylight versus dark hours. The abundance signals in our data reflected biological variation rather than stochastic variation, since replicates taken at the same hour were more similar to each other than those taken at different hours. Our compositional results indicated a dynamic community, rather than a static pool of eDNA—even across a few hours. The fish data showed a daily pattern of relative species abundances, and the uncoupling of fish and broader eukaryote data suggest that variation in eDNA profiles across a single day can provide valuable information reflecting diel changes, at least for highly mobile organism groups. However, our results also point to several pitfalls in current eDNA experimental design, in which samples are taken over large areas without relative time‐consistency or short‐term replication. Our findings shed new light on short‐term variation in coastal eDNA and have wide implications for experimental study design and for incorporating temporality into project conceptualization for future aquatic biodiversity monitoring.
Myocarditis following mRNA COVID‐19 vaccination: call for endomyocardial biopsy
Authors: Kiblboeck Daniel , Klingel Karin , Genger Martin , Traxler Selina , Braunsteiner Nathalie , Steinwender Clemens , Kellermair Joerg
Published: February 2022

Acute myocarditis following mRNA COVID‐19 vaccination was reported by the European Medicine Agency safety committee as a rare adverse event. We present a case series of three young male patients with suspected acute myocarditis following BNT162b2 mRNA COVID‐19 vaccination including results of endomyocardial biopsies (EMB). Additionally, we analysed EMB of another 21 patients with clinically suspected acute myocarditis following vaccination to determine the pathohistological pattern. Overall, EMB revealed acute lymphocytic myocarditis in 5 (20.8%), chronic lymphocytic myocarditis in 6 (25%), cardiac sarcoidosis in 1 (4.2%), healed myocarditis in 6 (25%), and other diagnoses with cardiac damage of unclear aetiology in 6 (25%) cases. Our findings support the necessity of EMB in patients with suspected acute myocarditis following mRNA COVID‐19 vaccination presenting with reduced EF to establish a correct and definite diagnosis. Concerns of these rare severe adverse events after COVID‐19 immunization should not undermine its value for the global community.
Facile Synthesis of a Conjugated Macrocyclic Nanoring with Graphenic Hexabenzocoronene Sidewall as the Segment of [12,12] Carbon Nanotubes
Authors: Wang Shengda , Li Xingcheng , Wei Kang , Zhang Xinyu , Yang Shangfeng , Zhuang Guilin , Du Pingwu
Published: February 2022

Herein, we report a facile synthesis of a conjugated macrocyclic nanoring, cyclo[9]paraphenylene‐2,11‐hexabenzocoronenylene ([9]CPPH2,11) with graphenic hexabenzocoronene sidewall by Suzuki–Miyaura cross‐coupling reaction. The structure of [9]CPPH2,11 was confirmed by HR‐MS and NMR. The photophysical properties were studied using UV/Vis and photoluminescence spectroscopy. Possessing unique structural and physical properties, this conjugated macrocyclic nanoring with a graphenic hexabenzocoronene sidewall can expand the scope of bottom‐up synthesis of uniform carbon nanotube segments and potential applications in hole‐ and electron‐ transport devices.
The effect of mental countermeasures on a novel brain‐based feedback concealed information test
Authors: Zheng Jinbin , Cheng Jiayu , Wang Chongxiang , Lin Xiaohong , Fu Genyue , Sai Liyang
Published: February 2022

The feedback concealed information test (fCIT) is a novel form of the CIT, providing participants with feedback regarding their memory concealment performance. The fCIT utilizes event‐related potentials (recognition‐P300 and feedback‐related event‐related potentials) and has been shown to provide high efficiency in detecting information concealment. However, it is unclear how well the fCIT performs in the presence of mental countermeasures. To address this question, participants were trained to use countermeasures during fCIT. Results showed that the recognition‐P300 efficiency decreased when participants used countermeasures. However, the efficiencies of feedback‐related negativity and feedback‐P300 were unchanged, with feedback‐P300 still showing a high detection efficiency (AUC = 0.86) during countermeasures. These findings demonstrate the potential of fCIT for subverting countermeasures.
Experimental investigation of transient thermal characteristics of a dry friction clutch using alternative friction materials under different operating conditions
Authors: Sherzaa Jenan S. , Hussain Ihsan Y. , Abdullah Oday I.
Published: February 2022

The thermal characteristics of four types of dry friction clutch materials (LUK, G95, HCC, and Tiger) are investigated experimentally and numerically in the present work under different working conditions; such as initial sliding angular velocity (ωro), torque (T), and sliding time (ts). The temperature distributions over a cross‐section of friction clutch elements (pressure plate and flywheel) are investigated and optimized during the sliding period (heating phase), and full engagement period (cooling phase). The effect of alternative frictional materials lining of a clutch disc on the thermal behavior of the sliding system under different operating conditions (different angular velocities, torques, and sliding periods) is investigated experimentally. The results showed that the maximum effect on the temperature values occurred when applying maximum torque (4.5 kg·m), maximum initial rotational speed (1200 rpm), slipping period (30 s). However, the temperature values at interface contact decrease when decreasing all the above input conditions values to (2.5 kg·m, 690 rpm, and slipping period to 8 s). The results showed that the temperature reduced (53%) from (180.4°C) for applied torque 4.5 kg·m with initial rotational speed (1200 rpm) and slip period (30 s) to (83.3°C) when applied torque 2.5 kg·m, initial rotational speed (680 rpm) and slip period (8 s) for clutch disc (LUK). It was obtained the same behavior for the other three discs (G95, HCC, and Tiger), but with different values of temperatures. The results show that the temperatures of the pressure plate interface (Tmax = 159.1°C) are higher than those at the flywheel interface (Tmax = 152.7°C), due to the low thermal capacity of pressure plate compared to the flywheel when using G95 frictional material. The experimental optimization results showed that the highest temperatures were obtained when using friction clutch disc (LUK), and minimum temperature when using (HCC) disc, around (20%) reduction when replaced (LUK) material with (HCC) under the same working conditions (T = 4.5 kg·m, ωro = 1200 rpm, and ts = 30 s).
Entropy analysis in MHD Couette flow of chemically reacting viscoelastic fluid past a deformable porous channel
Authors: Das Utpal J. , Patgiri Indushri
Published: February 2022

Here, an investigation of MHD Couette flow of a chemically reacting viscoelastic fluid past a deformable porous layer with entropy generation using Walters liquid model has been considered. A binary, homogeneous, and isotropic mixture of fluid and solid phases in the porous medium is considered. The impact of heat source parameter and Soret effect are taken into account. The governing equations are solved analytically to obtain the expressions for solid displacement, fluid velocity, temperature, and concentration. The impact of relevant parameters on the flow system, temperature, concentration, mass transfer flux, entropy generation number, and Bejan number are discussed graphically. It is observed that solid displacement enhances due to the growth of drag and viscoelastic parameter, while it reduces due to rising volume fraction parameter. Fluid velocity rises when the volume fraction parameter increases. Rising Brinkmann number enhances the temperature, while Brinkmann number and Soret number reduces the species concentration. The irreversibility of heat transfer dominates the flow near the channel plates, while the effect of fluid friction irreversibility can be observed within the channel centerline region.
Investigating hydrologic controls on 26 Precambrian shield catchments using landscape, isotope tracer and flow metrics
Authors: Tafvizi Arghavan , James April L. , Yao Huaxia , Stadnyk Tricia A. , Ramcharan Charles
Published: February 2022

Although many studies focus on catchment classification, hydrologists are challenged to find the most important variables for a meaningful catchment classification, especially in the heterogeneous environment of the Precambrian Shield. This study investigates landscape controls on hydrologic response by conducting a catchment classification of 26 catchments located within two Precambrian Shield watersheds (Sturgeon–French–Nipissing [SNF] and Muskoka) in central and Northeastern Ontario, Canada, using combinations of landscape characteristics (e.g. topography, geology, landcover), hydrometric variables, and stable isotopes of δ18O and δ2H in river flow. Weekly to monthly surveys of δ18O and δ2H in river flow were collected between 2013 and 2019. Flow metrics (e.g. Pardé coefficient and coefficient of variation of streamflow) were generated for 14 of the 26 rivers between 2008 and 2018. Principal component analyses (PCA) and Hierarchical Clustering on Principal Components (HCPC) analyses were used to identify variables controlling catchment clustering according to their similarities for four different scenarios. Despite their similar location along the southern edge of the Precambrian Shield, the 26 catchments generally clustered by watershed (SNF and Muskoka) with some exceptions. Differences in wetland and lake area (%), mean slope, and % area covered by glacialacustrine and glaciofluvial outwash deposits were the most influential variables in catchment classification. A positive correlation between % wetland area and streamflow stable isotope damping ratios suggests greater % wetland area (with shallow and potentially seasonally variable surface areas and/or hydrologic connection) observed in the SNF catchments increases variability in the influence of evaporative enrichment in SNF catchments. The catchment classification analyses in combination with stable isotopes of δ18O and δ2H were functional tools to investigate the combined influences of diverse types of catchment characteristics that lead to differences in hydrometric response. These results could support future studies focusing on generating hydrologic models and representing wetlands connectivity in the region.
Structures, properties, and challenges of emerging 2D materials in bioelectronics and biosensors
Authors: Chen Fan , Tang Qing , Ma Tian , Zhu Bihui , Wang Liyun , He Chao , Luo Xianglin , Cao Sujiao , Ma Lang , Cheng Chong
Published: February 2022

Bioelectronics are powerful tools for monitoring and stimulating biological and biochemical processes, with applications ranging from neural interface simulation to biosensing. The increasing demand for bioelectronics has greatly promoted the development of new nanomaterials as detection platforms. Recently, owing to their ultrathin structures and excellent physicochemical properties, emerging two‐dimensional (2D) materials have become one of the most researched areas in the fields of bioelectronics and biosensors. In this timely review, the physicochemical structures of the most representative emerging 2D materials and the design of their nanostructures for engineering high‐performance bioelectronic and biosensing devices are presented. We focus on the structural optimization of emerging 2D material‐based composites to achieve better regulation for enhancing the performance of bioelectronics. Subsequently, the recent developments of emerging 2D materials in bioelectronics, such as neural interface simulation, biomolecular/biomarker detection, and skin sensors are discussed thoroughly. Finally, we provide conclusive views on the current challenges and future perspectives on utilizing emerging 2D materials and their composites for bioelectronics and biosensors. This review will offer important guidance in designing and applying emerging 2D materials in bioelectronics, thus further promoting their prospects in a wide biomedical field.

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Diversity, composition, and freedom to choose drive the effects of St. Augustinegrass cultivar blends on an herbivorous insect
Authors: Doherty Ethan M. , Meagher Robert L. , Dale Adam G.
Published: February 2022

Warm‐season turfgrasses are conventionally produced and maintained as cultivar monocultures, which leaves them less resilient to pest attack than more diverse plantings. Recent evidence has indicated that mixing St. Augustinegrass [Stenotaphrum secundatum (Walter) Kuntze] cultivars can provide pest management benefits compared with cultivar monocultures. Research in other systems has shown that the effects of plant diversity on herbivores often depends on the number and identity of plant species present. Host plant diversity can affect herbivore fitness via postconsumptive physiological effects or before consumption by influencing herbivore behavior or plant defenses. To investigate the mechanisms by which St. Augustinegrass cultivar diversity and composition affect an insect herbivore, six cultivars were mixed to create two levels of cultivar diversity, and fall armyworm life history traits were tracked under no‐choice diet mixing conditions and conditions where the larvae could forage among mixed cultivars. These experiments demonstrated that specific cultivar blends can reduce herbivore fitness and herbivory, and that the effects on fall armyworm fitness are likely driven by insect–plant interactions rather than postconsumptive physiological effects. The results will inform pest management strategies in warm‐season turfgrass production and management, adding to the literature focused on the effects of intraspecific plant diversity.
Training supervisors to provide performance feedback using video modeling with voiceover instructions: A replication
Authors: Carroll Regina A. , Preas Elizabeth J. , Paden Amber R.
Published: February 2022

Performance feedback is an effective strategy to improve and maintain therapist performance with implementing interventions. Shuler and Carroll (2019) successfully used video modeling with voiceover instructions (VMVO) to train supervisors to provide accurate performance feedback to a confederate therapist implementing guided compliance. In Study 1, we replicated Shuler and Carroll by using VMVO to train 5 supervisors to provide performance feedback to a confederate therapist on their guided‐compliance integrity. Feedback accuracy increased following VMVO and maintained for 1 month. In Study 2, we extended Shuler and Carroll by demonstrating improvements in therapist guided‐compliance integrity after they received performance feedback from supervisors from Study 1. The results of the current study support the use of VMVO to teach supervisory skills to behavior analysts.
Internalizing symptoms among Taiwanese adolescents in poverty: Longitudinal influences of neighborhood, family, and school
Authors: Chiang Shou‐Chun , Bai Sunhye
Published: February 2022

Introduction

Identifying specific contextual factors that contribute to the development of internalizing symptoms in adolescents in poverty is critical for prevention. This study examined the longitudinal effects of neighborhood disadvantage, family cohesion, and teacher–student relationship on adolescent internalizing symptoms from economically disadvantaged families.

Methods

Participants were 1404 Taiwanese adolescents (49% female) in the nationally representative Taiwan database of children and youth in poverty. Youth were enrolled in the seventh, eighth, or ninth grades (Time 1; Mage = 14.85, SD = 0.95) and completed biennial follow‐up assessments 2 (Time 2; Mage = 16.47, SD = 0.74) and 4 years after baseline (Time 3; Mage = 18.21, SD = 0.70). Latent growth models examined longitudinal associations between contextual factors and internalizing symptoms over time.

Results

Adolescents reported declines in neighborhood disadvantage and teacher–student relationship but increases in family cohesion over the 4 years. At baseline, greater neighborhood disadvantage was associated with higher levels of internalizing symptoms, whereas higher family cohesion was associated with lower levels of internalizing symptoms. Over time, an increase in family cohesion was associated with a decrease in internalizing symptoms.

Conclusion

This study provides empirical support that family cohesion plays a critical role in shaping the development of adolescent internalizing symptoms despite poverty. There was an increase in family cohesion from early to late adolescence among Taiwanese adolescents in poverty and such change was correlated with decreases in youth internalizing symptoms. Family cohesion may be a key target of prevention programs aiming to reduce internalizing symptoms for youth in poverty.
Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta
Authors: Omosule Catherine L. , Joseph Dominique , Weiler Brooke , Gremminger Victoria L. , Silvey Spencer , Jeong Youngjae , Rafique Ashique , Krueger Pamela , Kleiner Sandra , Phillips Charlotte L.
Published: February 2022

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).
Hemostatic effects of therapeutic plasma exchange: A concise review
Authors: Soares Ferreira Júnior Alexandre , Hodulik Kimberly , Barton Karen D. , Onwuemene Oluwatoyosi A.
Published: February 2022

Therapeutic plasma exchange (TPE) alters the hemostatic balance. Contributing to TPE's hemostatic effects is the mechanical processing of blood in the extracorporeal circuit, circuit anticoagulant, type of replacement fluid, TPE schedule and number of procedures, TPE timing relative to invasive procedures, and removal of nontargeted components such as platelets, coagulation proteins, and cytokines. Although TPE's hemostatic effects are well established, how it impacts the bleeding risk is not clearly understood. In this concise review, we describe the effects of the above TPE‐related factors on hemostatic balance, present data on the effects of TPE on blood hemostasis, including its effects on platelet counts and clotting assays, and review the literature on the impact of TPE‐induced hemostatic changes on TPE‐associated bleeding events. Finally, we discuss risk factors associated with bleeding during TPE and review the literature on TPE‐associated hemostatic effects in the pediatric population.
Combined diagnosis of QF‐PCR and CNV‐Seq in fetal chromosomal abnormalities: A new perspective on prenatal diagnosis
Authors: Qiao Jinping , Yuan Jing , Hu Wenjun , Li Qin , Fang Huiqin , Xu Yuanhong , Dai Yaqian
Published: February 2022

Objective

This study aimed to evaluate the effect of QF‐PCR and CNV‐seq in diagnosing prenatal fetal chromosomal aberrations, explore the advantages and necessity of multimethod joint diagnosis.

Methods

We chose pregnant women with the indication of fetal chromosome examination in our hospital last year, collected 657 cases of amniotic fluid for QF‐PCR and CNV‐seq analyzes.

Results

While detecting aneuploidy, the coincidence rate of QF‐PCR and CNV‐seq was 100% (56/56). For all 46 chromosomes, 523 cases (79.60%, 523/657) coincided precisely, 128 cases (19.48%, 128/657) showed abnormality with CNV‐seq, 8 cases (1.22%, 8/657) revealed abnormality by QF‐PCR. In serological Down's syndrome screening, 328 cases showed a high risk of trisomy 21, of which CNV‐seq and QF‐PCR were consistent in 4 cases (1.22%, 4/328), CNV‐seq found 87 cases of CNVs in 78 samples except for chromosomal aneuploidy abnormalities, among these, 18 cases (20.69%, 18/87) were polymorphic, 7 cases (8.05%, 7/87) might cause disease, 13 cases (14.94%, 13/87) caused disease explicitly, 21 cases (24.14%, 21/87) were possibly benign, 17 cases (19.54%, 17/87) were explicitly benign, and the classification of 11 cases (12.64%, 11/87) was unclear.

Conclusion

QF‐PCR and CNV‐seq were highly consistent in diagnosing chromosomal aneuploidy. The high risk of serological Down's screening might not only due to the aneuploidy of chromosomes 21, 18, and NTD, but also the microdeletion or microduplication of all 46 chromosomes. So using CNV‐seq combined with QF‐PCR could effectively reduce the risk of missed diagnosis.
The relationship between anger and suicidal ideation: Investigations in two samples
Authors: Schafer Katherine Musacchio , Daurio Allison , French Juliana E. , Rogers Megan L. , Meltzer Andrea L. , Cougle Jesse R. , Joiner Thomas E.
Published: February 2022

Objectives

Suicidal ideation (SI) nearly always precedes lethal suicide attempts. Anger may play a role in SI, but this appears to vary by gender and nuances in this relationship are unclear.

Method

We investigated whether levels of (a) anger and (b) SI vary by gender, (c) the cross‐sectional relationship between anger and SI, and (d) if gender moderates that relationship in two samples: adults seeking care for excessive anger (Study 1) and undergraduates endorsing previous suicide attempt (Study 2).

Results

In Study 1, anger was more commonly endorsed in women; however, in Study 2, anger did not vary by gender. In both studies, SI did not vary by gender. Further, in both studies, anger and SI were positively related. The relationship between anger and SI did not vary by gender in either study.

Conclusions

The strength of the relationship between anger and SI did not vary by gender.
Effect of water sampling strategies on the uncertainty of phosphorus load estimation in subsurface drainage discharge
Authors: Dialameh Babak , Ghane Ehsan
Published: February 2022

Accurate phosphorus (P) load estimation in subsurface drainage water is critical to assess the field‐scale efficacy of conservation practices. The HydroCycle‐PO4 instrument measures real‐time total reactive P (TRP) concentration without the need for sample filtration, thereby enabling comparative evaluation of different sampling strategies. The main objective of this study was to evaluate the effects of water sampling strategies on the uncertainty of P load estimation. Hourly TRP concentration and hourly drainage discharge measurements formed the reference P load dataset. Four hypothetical water sampling strategies were evaluated: (a) time‐proportional discrete sampling, (b) time‐proportional composite sampling, (c) flow‐proportional discrete sampling, and (d) flow‐proportional composite sampling. All sampling strategies underestimated TRP load compared with the reference dataset. Total reactive P load underestimation changed from 0.2 to 51% as time‐proportional discrete sampling intervals increased from 3 h to 14 d. Total reactive P load underestimation changed from 12 to 43% as the time‐proportional compositing scenario increased from 1 to 7 d, each with one aliquot per day. In the case of flow‐proportional discrete sampling scenario, the lowest (0.6%) and the highest (–5.1%) uncertainties were observed when 1‐ and 5‐mm flow intervals were used. The relative error based on the results provided by the flow‐proportional composite sampling ranged from 0.2% when using 1‐mm flow interval to –6.7% when using 5‐mm flow interval. In conclusion, the flow‐proportional sampling strategies provided a more accurate estimate of cumulative P load with fewer number of samples because a greater portion of samples were taken at higher flow rates compared with time‐proportional sampling strategies.
Exploring the role of Islam on the lived experience of patients with Long QT Syndrome in Saudi Arabia
Authors: Bakur Khadijah H. , Al‐Aama Jumana Y. , Alhassnan Zuhair N. , Brooks Helen , Clancy Tara , Manea Waleed , Takroni Saud A. , Ulph Fiona
Published: February 2022

Genetic services are rapidly growing in the Arab world leading to increasing number of patients being diagnosed with genetic disorders. Islam is the only/major religion of the local population in these countries. Muslim patients integrate religion in virtually every aspect of their lives, and it is vital to understand the role of Islam on their coping and decision‐making in the context of genetic counseling. This will help provide patients with the most appropriate services aligned to their religious beliefs and will improve outcomes. Increasing numbers of patients are being diagnosed with Long QT syndrome in Saudi Arabia. Using semi‐structured interviews, this study explored the role of Islam on the lived experience of 13 Saudi participants diagnosed with autosomal dominant Long QT syndrome (3/13) or who are carriers of Jervell and Lange‐Nielsen syndrome (10/13). The interviews investigated how they made sense of living with the condition in light of their religion/spirituality. The data were analyzed using interpretative phenomenological analysis and produced four superordinate themes: 1) Common belief and idiosyncratic interpretation; 2) Using religion to justify positive reframing of current illnesses; 3) Interplay between belief in medicine and in religion; and 4) Complex impact of diagnosis on religiosity. The results show that the participants’ idiosyncratic interpretations of the religious principles, not the principles themselves, had an important influence on their coping, medical decision‐making, perceptions regarding the cause of their disease, and compliance with medical advice. A novel insight of the current study is that the personal understanding and interpretation of medical information played the greatest role in the decision‐making process, and not the religious beliefs. Thus, it is important for health professionals to give patients’ information in a manner that is clear and detailed in order for them to facilitate an informed decision, and to ensure that they fully understand the implications.
Recovery of enzyme activity in biotinidase deficient individuals during early childhood
Authors: Forny Patrick , Wicht Andrea , Rüfenacht Véronique , Cremonesi Alessio , Häberle Johannes
Published: February 2022

Deficiency of the biotinidase (BTD) enzyme is an inborn error of biotin metabolism caused by biallelic pathogenic variants in the BTD gene. There are two forms, partial and profound BTD deficiency, which both can be successfully treated with pharmacological doses of biotin, justifying the inclusion of this disorder in the newborn screening in numerous countries. We investigated the BTD deficiency cohort (N = 87) in our metabolic center, as it was detected upon newborn screening since 2005, and aimed to better understand the long‐term course of BTD enzyme activity and how it may relate to the patients' genetic background. We observed that individuals with partial BTD deficiency display an elevation of BTD enzyme activity with increasing age in 48% of cases—a recovery which allowed adjustment or stop of biotin supplementation in 20% of all individuals. In addition, we were able to recruit 56 patients (64%) for genetic testing, revealing 19 different variants (2 novel), and constituting 22 different genotypes. Genotype–phenotype correlations revealed that the most abundant allele in our cohort p.(Asp444His) was also the most common variant in patients displaying recovery of BTD enzyme activity. Based on our results, we recommend to retest all patients with partial BTD deficiency at the age of 5 years, as this may result in an impact on therapy. Moreover, genetic testing of BTD deficient individuals can allow prediction of the severity of BTD deficiency and of the likelihood of BTD enzyme activity recovery with age.

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Leadership Style in Relation to Gender Role and Masculine Values: Being Daoist Water‐Like or Agentic?
Authors: Zhou Wen‐Qian , Lee Yueh‐Ting , Jacobs Eric
Published: February 2022

Based on the Daoist water‐like theory in relation to leadership and gender, the current study aims to compare two leadership styles (Daoist water‐like and Agentic) and their relation to the gender role of leaders and the masculine values of perceivers. A 2 × 2 × 2 between‐subjects factorial experiment (leader gender, leadership style, and perceiver masculinity value) was conducted to examine the favorability, empowerment, and democracy (FED) of the leader by using vignettes as stimulus materials. Participants (N = 383) were recruited from MTurk and were randomly assigned to evaluate the leader candidate in the vignette. Overall, the results indicated that Daoist water‐like leadership was perceived as more FED than agentic leadership. Moreover, Daoist water‐like male leadership was seen as the most FED, while the agentic male leadership style was seen as the least FED. Finally, perceivers with low masculine values tended to view the Daoist water‐like leadership as more FED than agentic leadership, while perceivers with high masculine values did not endorse agentic over Daoist water‐like leadership. Implications of the Daoist water‐like leadership in relation to the gender role of the leader and masculine values of the perceiver are discussed.
Forecasting neuromuscular recovery after anterior cruciate ligament injury: Athlete recovery profiles with generalized additive modeling
Authors: Jordan Matthew J. , Morris Nathaniel , Barnert Jeremiah , Lawson Drew , Aldrich Witt Isabel , Herzog Walter
Published: February 2022

A retrospective analysis of longitudinally collected athlete monitoring data was conducted to generate a model of neuromuscular recovery after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Neuromuscular testing data including countermovement jump (CMJ) force‐time asymmetries and knee extensor strength (maximum voluntary contractionext) asymmetries (between‐limb asymmetry index—AI) were obtained from athletes with ACLR using semitendinosus (ST) autograft (n = 29; AI measurements: n = 494), bone patellar tendon bone autograft (n = 5; AI measurements: n = 88) and noninjured controls (n = 178; AI measurements: n = 3188). Explosive strength measured as the rate of torque development was also calculated. CMJ force‐time asymmetries were measured over discrete movement phases (eccentric deceleration phase, concentric phase). Separate additive mixed effects models (additive mixed effects model [AMM]) were fit for each AI with a main effect for the surgical technique and a smooth term for the time since surgery (days). The models explained between 43% and 91% of the deviance in neuromuscular recovery after ACLR. The mean time course was generated from the AMM. Comparative neuromuscular recovery profiles of an athlete with an accelerated progression and an athlete with a delayed progression after a serious multiligament injury were generated. Clinical Significance: This paper provides a new perspective on the utility of longitudinal athlete monitoring including routine testing to develop models of neuromuscular recovery after ACLR that can be used to characterize individual progression throughout rehabilitation.
Fabrication and characterization of chitosan nanoparticles using the coffee‐ring effect for photodynamic therapy
Authors: Bekmukhametova Alina , Uddin Mir Muhammad Nasir , Houang Jessica , Malladi Chandra , George Laurel , Wuhrer Richard , Barman Shital K. , Wu Ming J. , Mawad Damia , Lauto Antonio
Published: February 2022

Background and Objectives

Biocompatible nanoparticles have been increasingly used in a variety of medical applications, including photodynamic therapy. Although the impact of synthesis parameters and purification methods is reported in previous studies, it is still challenging to produce a reliable protocol for the fabrication, purification, and characterization of nanoparticles in the 200–300 nm range that are highly monodisperse for biomedical applications.

Study Design/Materials and Methods

We investigated the synthesis of chitosan nanoparticles in the 200–300 nm range by evaluating the chitosan to sodium tripolyphosphate (TPP) mass ratio and acetic acid concentration of the chitosan solution. Chitosan nanoparticles were also crosslinked to rose bengal and incubated with human breast cancer cells (MCF‐7) to test photodynamic activity using a green laser (λ = 532 nm, power = 90 mW).

Results

We established a simple protocol to fabricate and purify biocompatible nanoparticles with the most frequent size occurring between 200 and 300 nm. This was achieved using a chitosan to TPP mass ratio of 5:1 in 1% v/v acetic acid at a pH of 5.5. The protocol involved the formation of nanoparticle coffee rings that showed the particle shape to be spherical in the first approximation. Photodynamic treatment with rose bengal‐nanoparticles killed ~98% of cancer cells.

Conclusion

A simple protocol was established to prepare and purify spherical and biocompatible chitosan nanoparticles with a peak size of ~200 nm. These have remarkable antitumor activity when coupled with photodynamic treatment.
New examples of canonical covers of degree 3
Authors: Bin Nguyen
Published: February 2022

This paper presents new examples of projective surfaces of general type over with canonical map of degree 3 onto a surface of general type. Very few examples are known of such surfaces and some of the examples in this paper present the new feature of having the canonical map not a morphism (i.e. the canonical linear system with base points).
Existence and uniqueness of solution for a nonlinear fractional problem involving the distributional Riesz derivative
Authors: Abada Esma , Lakhal Hakim , Maouni Messaoud
Published: February 2022

In this article, we prove the existence of weak solutions for the following nonlinear problem that contains a nonlocal operator −Ds · (ADs(.)) which is defined by the distributional Riesz fractional derivatives and a measurable, bounded, positive definite matrix A(x).

where
is a bounded open set with a Lipschitz boundary, s ∈ (0, 1) and n > 2s. Under some suitable conditions on the nonlinear term f and the matrix A(x), it has shown that this problem has at least one weak solution u. We use in our proof the Leray–Schauder degree method to prove the existence of weak solutions and the Banach fixed point theorem to prove the uniqueness of weak solution in a particular case.