bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing a Baculovirus/Insect Cell Expression System and Expressed Protein Ligation (EPL) for Protein Semisynthesis
Authors: Butts Marie , Chu Nam
Published: January 2022

Protein semisynthesis has been used for the chemoselective linking of synthetic peptides and recombinant protein fragments to generate complete native proteins in good yield. The ability to site‐selectively incorporate multiple post‐translational chemical modifications (PTMs) into proteins via this approach shows great potential for enhancing understanding of the molecular basis of protein function and regulation. Protein semisynthesis, however, often requires high expression efficiency of the recombinant protein fragments (i.e., high expression yield and ability to preserve protein biological functions), which can be hard to achieve for some human enzymes when using bacterial expression systems. Here, we describe how to use a baculovirus/insect cell expression system and a protein semisynthesis strategy known as expressed protein ligation (EPL) to produce workable levels of proteins of interest containing site‐specific chemical modifications. The protocol provides detailed guidance for generating protein C‐terminal thioesters for use with the EPL reaction, performing the EPL reaction, and purifying the protein ligation product. We exemplify the protocols by generating protein kinase Akt1 with site‐specific phosphorylations installed into its C‐terminal tail, for kinetic kinase assays. We hope these methods will help increase the use of protein semisynthesis for elucidating the post‐translational regulation of human enzymes involved in cell signaling. © 2022 Wiley Periodicals LLC

Basic Protocol 1: Generation of the N‐terminal protein of interest (POI) fragment containing a C‐terminal thioester moiety

Basic Protocol 2: Expressed protein ligation (EPL) of the protein thioester with a synthetic peptide and purification of the protein ligation product

Basic Protocol 3: Semisynthesis and biochemical analysis of site‐specifically phosphorylated Akt1
Adverse childhood experiences predict neurite density differences in young children with and without attention deficit hyperactivity disorder
Authors: Hare Megan M. , Dick Anthony Steven , Graziano Paulo A.
Published: January 2022

Adverse childhood experiences (ACEs) put millions of children at risk for later health problems. As childhood represents a critical developmental period, it is important to understand how ACEs impact brain development in young children. In addition, children with attention‐deficit/hyperactivity disorder (ADHD) are more likely than typically developing (TD) peers to experience ACEs. Therefore, the current study examined the impact of ACEs on early brain development, using a cumulative risk approach, in a large sample of children with and without ADHD. We examined 198 young children (Mage = 5.45, 82.3% Hispanic/Latino; 52.5% ADHD) across measures of brain volume, cortical thickness, neurite density index (NDI), and orientation dispersion index (ODI). For the NDI measure, there was a significant interaction between group and cumulative risk (ß = .18, p = .048), such that for children with ADHD, but not TD children, greater cumulate risk was associated with increased NDI in corpus callosum. No other interactions were detected. Additionally, when examining across groups, greater cumulative risk was associated with reduced ODI and volume in the cerebellum, although these findings did not survive a correction for multiple comparisons. Our results highlight the role early cumulative ACEs play in brain development across TD and children with ADHD.
Prenatal exposure to maternal psychological distress and telomere length in childhood
Authors: Stout‐Oswald Stephanie A. , Glynn Laura M. , Bisoffi Marco , Demers Catherine H. , Davis Elysia Poggi
Published: January 2022

Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy‐related anxiety) and TL in childhood. Participants included 102 children (54 girls) and their mothers. Mothers’ distress was assessed five times during pregnancy, at 12 weeks postpartum, and at the time of child telomere measurement between 6 and 16 years of age. Maternal distress during pregnancy predicted shorter offspring TL in childhood, even after accounting for postnatal exposure to maternal distress and other covariates. These findings indicate that maternal mental health predicts offspring TL biology later in childhood than previously observed. This study bolsters claims that telomere biology is subject to fetal programming and highlights the importance of supporting maternal mental health during pregnancy.
Detection of bazedoxifene, a selective estrogen receptor modulator, in human urine by liquid chromatography‐tandem mass spectrometry
Authors: Okano Masato , Sato Mitsuhiko , Kageyama Shinji
Published: January 2022

Bazedoxifene, a selective estrogen receptor modulator, has been explicitly included in the prohibited list issued by the World Anti‐Doping Agency (WADA) since January 2020. A high‐resolution liquid chromatography–tandem mass spectrometric detection method was developed to identify bazedoxifene and its metabolites in human urine and to quantify bazedoxifene (free plus glucuronide) for doping control purposes. Bazedoxifene acetate (20 mg) was orally administered to seven male volunteers, and the urine samples collected were analyzed using the developed method. The linearity ranged from 0.5 to 200 ng/ml, and the limit of detection was <0.2 ng/ml. The interday precision (2.2% to 3.6%) and the interday accuracy (−10.0% to 1.9%) were adequate. Bazedoxifene, bazedoxifene–N‐oxide, and bazedoxifene glucoconjugates were identified in the urine samples. The profiles of the urinary excretion indicated the presence of small amounts of free bazedoxifene and bazedoxifene–N‐oxide, whereas bazedoxifene glucuronide was the predominant metabolite. The cumulative excretion amount of bazedoxifene (free form plus glucuronide conjugate) within 78 h after the administration was 0.7% to 1.3% of the total dose. In all subjects, bazedoxifene (free plus glucuronide) could be detected in urine up to 78 h after administration.
Five‐year follow‐up of intracoronary autologous cell therapy in acute myocardial infarction: the REGENERATE‐AMI trial
Authors: Mathur Anthony , Sim Doo Sun , Choudry Fizzah , Veerapen Jessry , Colicchia Martina , Turlejski Tymoteusz , Hussain Mohsin , Hamshere Stephen , Locca Didier , Rakhit Roby , Crake Tom , Kastrup Jens , Agrawal Samir , Jones Daniel A. , Martin John
Published: January 2022

Aims

The long‐term outcomes of the intracoronary delivery of autologous bone marrow‐derived cells (BMCs) after acute myocardial infarction are not well established. Following the promising 1 year results of the REGENERATE‐AMI trial (despite it not achieving its primary endpoint), this paper presents the analysis of the 5 year clinical outcomes of these acute myocardial infarction patients who were treated with an early intracoronary autologous BMC infusion or placebo.

Methods and results

A 5 year follow‐up of major adverse cardiac events (defined as the composite of all‐cause death, recurrent myocardial infarction, and all coronary revascularization) and of rehospitalization for heart failure was completed in 85 patients (BMC n = 46 and placebo n = 39). The incidence of major adverse cardiac events was similar between the BMC‐treated patients and the placebo group (26.1% vs. 18.0%, P = 0.41). There were no cases of cardiac death in either group, but an increase in non‐cardiac death was seen in the BMC group (6.5% vs. 0%, P = 0.11). The rates of recurrent myocardial infarction and repeat revascularization were similar between the two groups. There were no cases of rehospitalization for heart failure in either group.

Conclusion

This 5 year follow‐up analysis of the REGENERATE‐AMI trial did not show an improvement in clinical outcomes for patients treated with cell therapy. This contrasts with the 1 year results which showed improvements in the surrogate outcome measures of ejection fraction and myocardial salvage index.
π‐Extended Helical Nanographenes: Synthesis and Photophysical Properties of Naphtho[1,2‐a]pyrenes**
Authors: Chalifoux Wesley A. , Sitaula Paban , Malone Ryan J. , Longhi Giovanna , Abbate Sergio , Gualtieri Eva , Lucotti Andrea , Tommasini Matteo , Franzini Roberta , Villani Claudio , Catalano Vincent J.
Published: January 2022

A mild and efficient synthesis of a broad scope of substituted naphtho[1,2‐a]pyrene derivatives was accomplished in good yields using an InCl3/AgNTf2‐mediated two‐fold alkyne benzannulation reaction. HPLC enantiomeric separation was achieved and the interconversion barriers have been determined. The ECD spectra of two derivatives were recorded and interpreted through TD‐DFT calculations. Raman spectra were also recorded and predicted through DFT calculations.
Genome‐wide association studies of 27 accelerometry‐derived physical activity measurements identified novel loci and genetic mechanisms
Authors: Qi Guanghao , Dutta Diptavo , Leroux Andrew , Ray Debashree , Muschelli John , Crainiceanu Ciprian , Chatterjee Nilanjan
Published: January 2022

Physical inactivity (PA) is an important risk factor for a wide range of diseases. Previous genome‐wide association studies (GWAS), based on self‐reported data or a small number of phenotypes derived from accelerometry, have identified a limited number of genetic loci associated with habitual PA and provided evidence for involvement of central nervous system in mediating genetic effects. In this study, we derived 27 PA phenotypes from wrist accelerometry data obtained from 88,411 UK Biobank study participants. Single‐variant association analysis based on mixed‐effects models and transcriptome‐wide association studies (TWAS) together identified 5 novel loci that were not detected by previous studies of PA, sleep duration and self‐reported chronotype. For both novel and previously known loci, we discovered associations with novel phenotypes including active‐to‐sedentary transition probability, light‐intensity PA, activity during different times of the day and proxy phenotypes to sleep and circadian patterns. Follow‐up studies including TWAS, colocalization, tissue‐specific heritability enrichment, gene‐set enrichment and genetic correlation analyses indicated the role of the blood and immune system in modulating the genetic effects and a secondary role of the digestive and endocrine systems. Our findings provided important insights into the genetic architecture of PA and its underlying mechanisms.
Numerical study on combined convection heat transfer flow problem in a porous corrugated enclosure
Authors: Choudhary Pankaj , Ray Rajendra K.
Published: January 2022

In this study, we numerically analyzed the unsteady two‐dimensional combined convection flow problem in a porous‐corrugated enclosure whose upper wall is moving with uniform velocity associated with sinusoidal temperature distribution. The vertical sidewalls of the porous‐corrugated enclosure are kept at constant cold temperature while square‐shaped undulations at the bottom wall are discretely heated. Five different cases are considered depending on the discrete isothermal heating. In this paper, we have used the vorticity‐stream‐function formulation of the Brinkmann‐extended Darcy model to numerically simulate the momentum transfer in a porous‐corrugated enclosure. A transformation‐free higher‐order compact (HOC) scheme is used to discretize the nonlinear coupled transport equations, and an advanced iterative solver, like the hybrid‐bi‐conjugate‐gradient stabilized technique, is used to solve the system of algebraic equations generated from the numerical discretization. The present higher‐order compact scheme is fourth‐order accurate in space coordinates and second‐order accurate in the time variable. The numerically simulated results are analyzed over a range of key parameters, like Darcy number , Reynolds Number , Prandtl number , and with fixed high Grashof number , to study the effects of these leading parameters on the characteristics of heat transfer, fluid flow and isothermal distributions in the porous‐corrugated enclosure. These numerically computed results are presented in the form of streamlines, isotherms, Nusselt number plots, and so forth. Our computed results show numerous flow features which have not been studied previously.
The impact of partially absorbable midurethral slings in stress urinary incontinence surgery: A cohort study
Authors: Ng‐Stollmann Nathalie , Fünfgeld Christian , Hüsch Tanja
Published: January 2022

Objective

To evaluate the performance of retropubic midurethral slings (MUS) for the treatment of female stress urinary incontinence (SUI) at a certified continence center and to identify risk factors for sling failure.

Methods

This was a single‐center cohort study including women who underwent a retropubic MUS procedure for SUI between 2012 and 2019 with a follow up of 12 months. Primary end point was cure of SUI assessed using the validated questionnaire International Consultation of Incontinence Questionnaire—Urinary Incontinence—Short Form. Univariate and multivariate analyses were applied to identify risk factors for sling failure. Wilcoxon signed‐rank tests were used as paired samples tests. The significance level was set at 5%.

Results

A total of 662 women with a median age of 65 years (interquartile range 19 years) were included in the investigation; 523 (79.0%) presented with complicated SUI. Cure was reported by 213 (32.2%) women. Independent predictors for failure were obesity, pharmacotherapy for overactive bladder, postoperative sling adjustment, and use of partially absorbable mesh, which was correlated with a 56% decrease in the odds for achieving cure.

Conclusion

This investigation questions the role of partially absorbable mesh for stress urinary incontinence procedures and scrutinizes the use of implants with inadequate clinical evidence.
Native‐tissue prolapse repair: Efficacy and adverse effects of uterosacral ligaments suspension at 10‐year follow up
Authors: Cola Alice , Marino Giuseppe , Milani Rodolfo , Barba Marta , Volontè Silvia , Spelzini Federico , Manodoro Stefano , Frigerio Matteo
Published: January 2022

Objective

To evaluate the 10‐year outcomes of high uterosacral ligaments suspension as a primary repair for apical prolapse and to evaluate the long‐term impact of prognostic factors.

Methods

A retrospective study analyzed 10‐year follow up after repair of primary apical prolapse through high uterosacral ligament suspension. Bulging symptoms and postoperative prolapse stage II or above were considered subjective and objective recurrences, respectively. Patient Global Impression of Improvement score was used to evaluate subjective satisfaction after surgery.

Results

A total of 287 women were analyzed. Ten‐year recurrence rates were 19.1% for objective recurrence and 6.3% for subjective recurrence; surgical retreatment rate was 2.1%. Premenopausal status was related to 15‐fold increased risk of developing either objective or subjective recurrence. Conversely, anterior and posterior repair were protective factors against reoperation.

Conclusion

High uterosacral ligaments suspension is a safe and long‐lasting effective procedure for the treatment of uterovaginal prolapse even 10 years after index surgery. Premenopausal status and lack of anterior and posterior repair represented long‐term risk factors for surgical failure.
Can sonographic fetal head circumference measurement help predict obstetric anal sphincter injury?
Authors: Ortega Marcus V. , Kim Youngwu , Leung Katherine , Weinstein Milena , Leftwich Heidi K.
Published: January 2022

Objective

To investigate whether sonographic fetal head circumference (sfHC) size assessed by ultrasound prenatally could help predict OASIS.

Methods

This study is a retrospective cohort study between 2005 and 2016. Antenatal sfHC assessment, maternal demographics, and labor and delivery data were abstracted and compared in women with and without OASIS.

Results

Of 2057 pregnant women that had sfHC assessment, 121 (5.8%) had OASIS. In the unadjusted analysis, sfHC above the 90th centile was associated with OASIS (odds ratio [OR] 1.12; 95% confidence interval [CI] 1.02–1.23; P = 0.015). When adjusted for gestational age at delivery, maternal age, race, prolonged second stage, body mass index, infant gender, and intrapartum oxytocin use, sfHC above the 90th centile remained significantly associated with OASIS (OR 1.13, 95% CI 1.00–1.27, P = 0.050).

Conclusion

In our cohort, sfHC above the 90th centile was associated with a greater risk of OASIS. As OASIS significantly impacts both short‐term and long‐term health outcomes, such as perineal pain, dyspareunia, and urinary and fecal incontinence, sfHC could be an additional prenatal marker to help clinicians counsel pregnant women about the risk of OASIS.
Maternal and perinatal complications according to maternal age: A systematic review and meta‐analysis
Authors: Saccone Gabriele , Gragnano Elisabetta , Ilardi Bernadette , Marrone Vincenzo , Strina Ida , Venturella Roberta , Berghella Vincenzo , Zullo Fulvio
Published: January 2022

Objective

To evaluate the risk levels for maternal and perinatal complications at > 40, > 45 and > 50 years old compared with younger controls.

Methods

Electronic databases were searched from their inception until March 2021. We included studies reporting pregnancy outcome in pregnant women aged 40, 45, and 50 years or older compared with controls at the time of delivery. Case reports and case series were excluded. The primary outcome was the incidence of stillbirth. Meta‐analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Heterogeneity was measured using I2 (Higgins I2). Subgroup analyses in women older than 45 years and in those older than 50 years were performed.

Results

Twenty‐seven studies, including 31 090 631 women, were included in the meta‐analysis. The overall quality of the included studies was moderate to high. Most of the included studies were retrospective cohort studies (21/27), four were population‐based studies, and two were cross‐sectional studies. Women aged ≥40 years had significantly higher risk of stillbirth (RR 2.16, 95% CI 1.86–2.51), perinatal mortality, intrauterine growth restriction, neonatal death, admission to neonatal intensive care unit, pre‐eclampsia, preterm delivery, cesarean delivery, and maternal mortality compared with women younger than 40 years old (RR 3.18, 95% CI 1.68–5.98). The increased risks for maternal mortality were 42.76 and 11.60 for women older than 50 years and for those older than 45 years, respectively, whereas those for stillbirth were 3.72 and 2.32. The risk of stillbirth and cesarean delivery was significantly higher in women >45 years compared with those aged 40–45 years, and in those aged >50 years compared with those aged 45–50 years. The risk of maternal mortality was significantly higher in women aged >50 years compared with those aged 40–45 (RR 60.40, 95% CI 13.28–274.74).

Conclusion

The risk of stillbirth, cesarean delivery, and maternal mortality increases with advancing maternal age. The risk ratios for maternal mortality were 3.18, 11.60, and 42.76 in women older than 40, older than 45, and older than 50 years, respectively. These data should be used when women with advanced maternal age are counseled regarding their risk in pregnancy.

Systematic Review Registration

The review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration No.: CRD42020208788).
An ultrasonography‐based approach for tissue modelling to inform photo‐therapy treatment strategies
Authors: Kallepalli Akhil , Halls James , James David B. , Richardson Mark A.
Published: January 2022

Currently, diagnostic medicine uses a multitude of tools ranging from ionising radiation to histology analysis. With advances in piezoelectric crystal technology, high‐frequency ultrasound imaging has developed to achieve comparatively high resolution without the drawbacks of ionising radiation. This research proposes a low‐cost, non‐invasive and real‐time protocol for informing photo‐therapy procedures using ultrasound imaging. We combine currently available ultrasound procedures with Monte Carlo methods for assessing light transport and photo‐energy deposition in the tissue. The measurements from high‐resolution ultrasound scans are used as input for optical simulations. Consequently, this provides a pipeline that will inform medical practitioners for better therapy strategy planning. While validating known inferences of light transport through biological tissue, our results highlight the range of information such as temporal monitoring and energy deposition at varying depths. This process also retains the flexibility of testing various wavelengths for individual‐specific geometries and anatomy.
Immunomodulatory properties of nanostructured systems for cancer therapy
Authors: Comparetti Edson J. , Ferreira Natalia N. , Ferreira Leonardo M. B. , Kaneno Ramon , Zucolotto Valtencir
Published: January 2022

Based on statistical data reported in 2020, cancer was responsible for approximately 10 million deaths. Furthermore, 17 million new cases were diagnosed worldwide. Nanomedicine and immunotherapy have shown satisfactory clinical results among all scientific and technological alternatives for the treatment of cancer patients. Immunotherapy‐based treatments comprise the consideration of new alternatives to hinder neoplastic proliferation and to reduce adverse events in the body, thereby promoting immune destruction of diseased cells. Additionally, nanostructured systems have been proven to elicit specific immune responses that may enhance anti‐tumor activity. A new generation of nanomedicines, based on biomimetic and bioinspired systems, has been proposed to target tumors by providing immunomodulatory features and by enabling recovery of human immune destruction capacity against cancer cells. This review provides an overview of the aspects and the mechanisms by which nanomedicines can be used to enhance clinical procedures using the immune modulatory responses of nanoparticles (NPs) in the host defense system. We initially outline the cancer statistics for conventional and new treatment approaches providing a brief description of the human host defense system and basic principles of NP interactions with monocytes, leukocytes, and dendritic cells for the modulation of antitumor immune responses. A report on different biomimetic and bioinspired systems is also presented here and their particularities in cancer treatments are addressed, highlighting their immunomodulatory properties. Finally, we propose future perspectives regarding this new therapeutic strategy, highlighting the main challenges for future use in clinical practice.
Methylglyoxal induces ambience for cancer promotion in HepG2 cells via Warburg effect and promotes glycation
Authors: Sruthi C R , Raghu K. G.
Published: January 2022

Methylglyoxal (MGO) is a toxic, highly reactive metabolite derived mainly from glucose and amino acids degradation. MGO is also one of the prime precursors for advanced glycation end products formation. The present research was performed to check whether MGO has any role in the promotion of cancer in HepG2 cells. For this, cells were incubated with MGO (50 µM) for 24 h and subjected to various analyses. Aminoguanidine (200 µM) was positive control. The various biochemical and protein expression studies, relevant to the MGO detoxification system, oxidative stress, and glycolysis were performed. MGO caused the reduction of expression of GLO 1 (27%) and GLO 2 (11%) causing weakening of the innate detoxification system. This is followed by an increase of RAGE (95%), AGEs or methylglyoxal adducts. We also observed hypoxia via estimation of oxygen consumption rate and surplus reactive oxygen species (ROS) (24%). To investigate the off‐target effect of MGO we checked its effect on glucose transport, and its associated proteins. Glucose uptake was found to increase (15%) significantly with overexpression of GLUT 1 (35%). We also found a significant increase of glycolytic enzymes such as hexokinase II, phosphofructokinase 1, and lactate dehydrogenase along with lactate production. Observation of surplus ROS and enhanced glycolysis led us to check the expression of HIF 1α which is their downstream signaling pathway. Interestingly HIF 1α was found to increase significantly (35%). It is known that enhanced glycolysis and oxidative stress are catalysts for the overexpression of HIF 1α which in turn creates an ambience for the promotion of cancer. Aminoguanidine was able to prevent the adverse effect of MGO partially. This is the first study to show the potential of MGO for the promotion of cancer in the non‐tumorigenic HepG2 cells via the Warburg effect and glycation.
Helping patients master core conflictual relationship themes in psychotherapy
Authors: Grenyer Brin F. S. , Marceau Ely M.
Published: January 2022

An important component of case formulation is to understand the patient's difficulties in the context of their relationships. The Core Conflictual Relationship Theme (CCRT) method provides a clinical guide for understanding the narratives of relationship conflicts told during therapy. We follow the case of Barbara, a 60 year old with a long history of chronic shyness. Her narratives follow a common CCRT: she wishes to feel safe, but fears that others are out to get her, which makes her withdraw. These patterns have pervasively repeated themselves in the past, present, and across different relationships (self, family, partners, colleagues). The therapist responds carefully by creating safety, tolerating her fears, and working to overcome these CCRT patterns, thus reducing her impulse to withdraw from treatment. Psychotherapists from many theoretical orientations can learn how patients mastering these repetitive negative CCRTs can lead to more adaptive relationship patterns that improve their mental health.
Motivational dynamics in basic needs profiles: Toward a person‐centered motivation approach in engineering education
Authors: Bombaerts Gunter , Vaessen Bram
Published: January 2022

Background

While educators strive for optimal student motivation to enhance the quality of learning for all, different students attending the same course can have different needs. Person‐centered approaches on basic needs profiles, categorizing individuals into groups with similar motivational profiles, have the potential to inform the relationship between different variables per cluster and to support instructional design sensitive to student differences. However, they are still absent in engineering education research (EER).

Purpose/Hypothesis

This gap is addressed by analyzing the basic psychological needs of engineering students as potential mediators during a mandatory, first‐year course on the ethics and history of technology. The aims are thus to (1) determine whether distinct basic needs profiles can be identified and (2) investigate how students' motivation differed and evolved during the course for the different basic needs profiles.

Design/Methods

Two‐step cluster analyses, MANOVA, andt‐test analyses were conducted using the data collected from 1864 students with digital questionnaires completed at three points within a semester of a course.

Results

We construed four student profiles from the survey data based on the distinct roles of competence and autonomy, with post hoc tests showing relationships between meaningful differences in evaluation of course elements, motivation, course appreciations, and motivation dynamics.

Conclusions

The person‐centered approach is promising in engineering education design to answer differences in students' basic needs to improve the quality of learning for all. We showed that the person‐centered approach could also add important insights complementary to the variable‐centered approach in EER on dynamics of motivation for learning.
Quantification of the NA dependent change of shape in the image formation of a z‐polarized fluorescent molecule using vectorial diffraction simulations
Authors: Ströhl Florian , Bruggeman Ezra , Rowlands Christopher J. , Wolfson Deanna L. , Ahluwalia Balpreet S.
Published: January 2022

The point spread function of a fixed fluorophore with its dipole axis colinear to the optical axis appears donut‐shaped when seen through a microscope, and its light distribution in the pupil plane is radially polarized. Yet other techniques, such as photolithography, report that this same light distribution in the pupil plane appears as a solid spot. How can this same distribution lead to a spot in one case but a donut in the other? Here, we show how the tube lens of the system plays a critical role in determining this shape. Using a vectorial treatment of image formation, we simulate the relative contributions of both longitudinal and radial components to the image of a dipole emitter and thus show how the donut (typically reported for z‐polarized single molecule fluorescence microscopy) transforms into a solid spot (as commonly reported for photolithography) as the numerical aperture of the tube lens increases. We find that the transition point occurs around 0.7 NA, which is significantly higher than used for most microscopy systems and lower than for common photolithography systems, thus resolving the seeming paradox of dipole shape.
Moral distress in genetic counseling: A study of North American genetic counselors
Authors: Wadman Erin , Conway Laura , Garbarini Jennifer , Baker Maria
Published: January 2022

Moral distress is the phenomenon whereby healthcare providers experience the inability to take action or act in morally appropriate ways when encountering a morally compromising situation. The correlation of moral distress to burnout and resignation in nursing and other healthcare fields has led to increasing attention and concern among healthcare professionals to identify the sources of moral distress, as well as find ways to alleviate it. An online mix‐method survey was sent to NSGC members to gain information on (1) sources of moral distress, (2) emotions involved, (3) coping strategies, and (4) suggestions to alleviate it. The ProQOL 5 scale was included to measure genetic counselor compassion satisfaction, burnout, and secondary traumatic stress. Two hundred and thirteen genetic counselors from North America completed the survey. Forty‐eight percent of respondents experienced moral distress and five sources were identified. The sources were situations involving other providers, family members, professional responsibility, personal beliefs, and access. Those more likely to experience moral distress worked in a prenatal setting, were over the age of 50, and worked for more than 21 years. Genetic counselors were more likely to talk to a co‐worker for support, and seek social support, address the source of the problem, and sustain self through working with patients as coping strategies. Most genetic counselors recommended talking to another genetic counselor to alleviate moral distress. Moral distress did not correlate with genetic counselor burnout, but did correlate with higher levels of secondary traumatic stress (p < 0.01). Thirty‐two percent of genetic counselors considered leaving their specialty, and 23% considered leaving their profession based on their experience(s) with moral distress. Our study establishes the existence of moral distress in the genetic counseling field and supports the need for coping strategies and recommendations in order to alleviate future genetic counselor moral distress.
Raman spectroscopy detects adulterated counter‐ions in pharmaceuticals
Authors: Fuini Evan , Reimers Alexandra , Hudspeth Amber , Kucera Kaury , Light David
Published: January 2022

Raman spectroscopy provides accurate and cost‐effective quality control of pharmaceuticals, which is essential for maintaining the confidence of dispensing physicians and patient's adherence to therapeutic regimens. For drug salts that contain a counter‐ion, the active pharmaceutical ingredient and counter‐ion combination is optimized for the intended therapeutic effect. Drug salts with multiple alternative counter‐ions are developed, dosed, and regulated independently and case study one demonstrates how an adulterated medication can contain a different counter‐ion than the label claim. Three additional case studies are performed that showcase how Raman spectroscopy can be applied as a cost‐effective alternative detection technique of both label claim drug and counter‐ion when compared to more commonly used HPLC‐UV methods.
Eco‐environmental footprint and value chains of technology multinational enterprises operating in emerging economies
Authors: Attah‐Boakye Rexford , Adams Kweku , Yu Honglan , Koukpaki Adebayo Serge Francois
Published: January 2022

Drawing from signaling theory and the multinational global value chain (GVC) literature, this study examines a critical question “does the adoption of eco‐friendly technology improve firm value?”. In addressing this question, we test a panel dataset for 633 technology multinational enterprises (TMNEs) operating in 15 emerging economies and covering 10 years from 2009 to 2019. This paper provides new insight into the increasing CO2 emission concerns, especially from the emerging economies and household consumption perspectives. Our study reveals that the adoption of eco‐friendly technology by TMNE's GVC operations will increase firm value and increase total environmental spending. Consequently, CO2 footprints in emerging countries will be reduced. Our findings are robust, controlling for several firm‐level and country‐level variables in our analysis. The practical, managerial, and policy implications of our study are discussed.
A review of micro‐practices in commodity value chains in the global south
Authors: Siaw Daniel , Botchie David , Sarpong David
Published: January 2022

Micro‐practices in the commodity value chains (CVCs) have experienced dramatic evolution through digital technology (DT). This article reviews the literature to identify four critical periods in this evolutionary cycle, from 1980 to 2020, to explicate the dimensions through which DT has foregrounded the burgeoning patterns of change in practice. Focusing on three key levels of micro‐practices: farm level, production level, and institutional level, a nuanced analysis of the role of relevant stakeholders in mobilizing resources and provides support to leverage DT. Our study shows how stakeholders' receptiveness has facilitated the radical (re)construction of micro‐practices in CVC. Implications for theory and practice are outlined.
A transaction cost perspective on blockchain governance in global value chains
Authors: Chen Weifeng , Botchie David , Braganza Ashley , Han Hongdan
Published: January 2022

This study advances theoretical insights into blockchain adoption in the context of global value chains from a transaction cost theory perspective. The research has adopted an exploratory qualitative approach using the Netnography method to scrutinize the case of TradeLens—a thriving blockchain‐enabled ecosystem that Maersk and IBM jointly developed. This study applies textual and audiovisual data from company websites and social media. Our findings indicate blockchain technology's salient and strategic relevance in streamlining business processes, improving efficiency, enhancing visibility, transparency, and traceability for value creation in the global value chains. This investigation supports the notion that blockchain, as a disruptor, will transform global trade with the digital tools to share real‐time information and collaborate security to reduce search and information cost, policing and enforcement cost in global economic transactions and administrative friction in trade. In contrast, the bargaining cost will increase if the information for the transaction is hard to verify where human actor intervention will be required, implying relatively higher designing costs in codifying the agreements in smart contracts.
Reuse‐oriented data publishing: How to make the shared research data friendlier for researchers
Authors: Duan Qingyu , Wang Xiaoguang , Song Ningyuan
Published: January 2022

Data repositories are an essential component of data infrastructure. This article explores their functionalities with accompanying examples with a focus on open, quantitative data sets. Based on researcher needs, the principle of data friendliness is presented, which involves data context (data characteristics), research context (individual circumstances and research settings) and the context of reuse paths (conditions allowing access to, understanding of and use of data). An examination of data context suggests that metadata and data enrichment are required to provide successful data context. Enrichment is also required for orientation of the research context to provide greater insights across data sets. Finally the article considers the reuse paths, and the say that data paths intersect human interaction and how these are being addressed by different repositories. The review concludes that data repositories need to focus on how to present data that is fully interoperable and allows for reuse as well as access.
Impact of human immunodeficiency virus status on laryngeal cancer survival and locoregional control
Authors: Weinreb Samuel Franklin , Piersiala Krzysztof , Dhar Shumon Ian , Hillel Alexander T. , Akst Lee , Best Simon R. A.
Published: January 2022

Objectives

To compare long‐term outcomes of laryngeal cancer (LC) in people living with HIV (PLWH) versus uninfected individuals and determine how clinical and viral factors—such as demographics, cancer stage, HIV viral load, and CD4 nadir—contribute to these outcomes.

Methods

This was a retrospective case–control study of 749 patients seen for LC at a single tertiary care center between 2003 and 2017. Of these, 22 had HIV at the time of LC diagnosis, and they were matched in a 1:4 ratio to uninfected controls based on sex, presence of smoking history, and age at cancer diagnosis. Kaplan–Meier survival curves and Cox proportional hazards models were constructed to identify overall and disease‐free survival differences based on HIV status, as well as other clinical and viral factors.

Results

Compared to all uninfected individuals, PLWH were diagnosed with LC approximately 6 years younger (p = .013). 1‐, 2‐, and 5‐year overall survival for PLWH were 86.4% (63.4%–95.4%), 77.3% (53.7%–89.9%), and 65.8% (40.8%–82.2%), respectively following LC diagnosis, and HIV was not significantly associated with overall (HR = 3.34 [0.59–18.79]) or disease‐free survival (HR = 2.12 [0.71–6.36]). The incidence rate of locoregional recurrence among PLWH was 541 compared to 371 per 10,000 person‐years in controls, which were not significantly different (p = .420). Furthermore, among PLWH, peak viral load and CD4 nadir were not associated with overall or disease‐free survival.

Conclusion

While previous work has shown that HIV is associated with elevated risk of LC, survival did not differ significantly between PLWH and uninfected individuals in this study.

Level of evidence

3.
Prospective study of intense pulsed light versus pulsed dye laser with or without blue light in the activation of PDT for the treatment of actinic keratosis and photodamage
Authors: Abrouk Michael , Gianatasio Chloe , Li Yumeng , Waibel Jill S.
Published: January 2022

Background

Exposure to ultraviolet (UV) light from the sun is known to have a deleterious effect on the skin. Repeated insults to the dermal matrix from UV radiation result in the clinical signs of photodamage, including changes in skin elasticity, color, and texture. UV radiation also leads to the accumulation of DNA mutations and promotes tumor development, resulting in the formation of cutaneous precancerous and cancerous lesions. Continuous‐wave incoherent blue light, intense pulsed light (IPL), and pulsed dye laser (PDL) are safe and efficacious light sources commonly used for aminolevulinic acid photodynamic therapy (PDT). The aim of this study was to prospectively evaluate the efficacy of PDT for the treatment of photodamage and actinic keratoses using four different combinations of light sources: PDL, PDL + blue light, IPL, and IPL + blue light.

Study

A total of 220 patients with either photodamage or actinic keratosis (AK) were recruited from the Miami Dermatology Laser Institute (Miami, FL) and were assigned prospectively to undergo one PDT treatment with one of the four light options: PDL, PDL + blue light, IPL or IPL + blue light. Of the 220 patients enrolled in treatment groups, 214 patients completed the study. Of the 214 patients, 88 received treatment for AK, and 126 received treatment for photodamage. All patients gave their consent to participate in the study and to allow their photographs to be utilized for the purpose of scientific presentations.

Results

Treatment with IPL resulted in a 70.8% reduction of actinic keratoses at a 1‐month follow‐up. Treatment with IPL and blue light 84.4% reduction of actinic keratoses at 1 month follow up. Treatment with PDL 70.5% reduction of actinic keratoses at 1 month follow up. Treatment with PDL and blue light 69.3% reduction of actinic keratoses at 1 month follow up. Treatment with IPL resulted in an improvement score of 2.9. Treatment with IPL and blue light resulted in an improvement score of 3.0. Treatment PDL resulted in an improvement score of 1.5. Treatment with PDL and blue light resulted in an improvement score of 1.8.

Conclusion

Although all four treatment groups led to some improvement in signs of photoaging, IPL + blue light again demonstrated increased efficacy when compared to IPL, PDL, and PDL + blue light treatment groups. Results from our study were limited by an unequal distribution between treatment groups and a lack of follow‐up beyond a 1‐month period and warrant further research.
THE SHARECROPPER AND THE PRESIDENT: TWO LEADERS AT THE CROSSROADS OF DEMOCRACY
Authors: Larson Kate Clifford
Published: January 2022

The author discusses the civil rights leadership of Fannie Lou Hamer, who rose from humble beginnings as a “poor, Black, Mississippi sharecropper,” to deliver “searing testimony at the Democratic National Convention during a hearing in front of the national party’s Credentials Committee” on August 22, 1964. The author calls leaders like Hamer “natural born,” and contends these leaders “do not follow the traditional path to positions of power and influence—they don’t have access to the best schools, employment opportunities, financial resources, or powerful interpersonal relationships and connections that position them for leadership.” Hamer was “poorly educated and raised in extreme poverty in an era when African Americans were denied equality and basic citizenship rights.” She “developed literacies distinctly separate from the spotty education she received in underfunded and segregated Black schools in Mississippi…her leadership sparked a dramatic movement forward in the fight for civil rights. In 1968, at the DNC convention in Chicago, Hamer’s state delegation was seated on the floor and Mississippi’s all‐white party was turned away. When she stood at the podium as a delegate from Mississippi, she received a standing ovation. That year a record 340 Black delegates and alternates from across the country sat and voted for the party’s nominees.”
A pro‐pgroup with full normal Hausdorff spectra
Authors: Heras Iker de las , Klopsch Benjamin
Published: January 2022

For each odd prime p, we produce a 2‐generated pro‐pgroupGwhose normal Hausdorff spectrawith respect to five standard filtration series , namely the lowerp‐series, the dimension subgroup series, thep‐power series, the iteratedp‐power series and the Frattini series, are all equal to the full unit interval [0,1]. Here denotes the Hausdorff dimension function associated to the natural translation‐invariant metric induced by the filtration series .
Delay differential equations for the spatially resolved simulation of epidemics with specific application to COVID‐19
Authors: Guglielmi Nicola , Iacomini Elisa , Viguerie Alex
Published: January 2022

In the wake of the 2020 COVID‐19 epidemic, much work has been performed on the development of mathematical models for the simulation of the epidemic and of disease models generally. Most works follow the susceptible‐infected‐removed (SIR) compartmental framework, modeling the epidemic with a system of ordinary differential equations. Alternative formulations using a partial differential equation (PDE) to incorporate both spatial and temporal resolution have also been introduced, with their numerical results showing potentially powerful descriptive and predictive capacity. In the present work, we introduce a new variation to such models by using delay differential equations (DDEs). The dynamics of many infectious diseases, including COVID‐19, exhibit delays due to incubation periods and related phenomena. Accordingly, DDE models allow for a natural representation of the problem dynamics, in addition to offering advantages in terms of computational time and modeling, as they eliminate the need for additional, difficult‐to‐estimate, compartments (such as exposed individuals) to incorporate time delays. In the present work, we introduce a DDE epidemic model in both an ordinary and partial differential equation framework. We present a series of mathematical results assessing the stability of the formulation. We then perform several numerical experiments, validating both the mathematical results and establishing model's ability to reproduce measured data on realistic problems.
Implementation science in pediatric oncology: A narrative review and future directions
Authors: Phillips Charles A. , Barakat Lamia P. , Pollock Brad H. , Bailey L. Charles , Beidas Rinad S.
Published: January 2022

Implementation science (IS) has garnered attention within oncology, and most prior IS work has focused on adult, not pediatric, oncology. This narrative review broadly characterizes IS for pediatric oncology. It includes studies through 2020 using the following search terms in PubMed, Ovid Medline, and Cochrane: “implementation science,” “pediatric,” “childhood,” “cancer,” and “oncology.” Systematic review was not performed due to the limited number of heterogeneous studies. Of 216 articles initially reviewed, nine were selected as specific to IS and pediatric oncology. All nine examined oncologic supportive care, cancer prevention, or cancer control. The supportive care focus is potentially due to the presence of cooperative study groups such as the Children's Oncology Group, which efficiently drive cancer‐directed therapy changes through clinical trials. Future IS within pediatric oncology should embrace this ecosystem and focus on cancer control interventions that benefit patients across multiple cancer types and patients treated outside cooperative group studies.