bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Racial Disparities in Deep Brain Stimulation for Parkinson's Disease
Authors: Cramer Samuel W. , Do Truong H. , Palzer Elise F. , Naik Anant , Rice Abigail L. , Novy Savannah G. , Hanson Jacob T. , Piazza Amber N. , Howard Madeleine A. , Huling Jared D. , Chen Clark C. , McGovern Robert A.
Published: April 2022

We sought to determine whether racial and socioeconomic disparities in the utilization of deep brain stimulation (DBS) for Parkinson's disease (PD) have improved over time. We examined DBS utilization and analyzed factors associated with placement of DBS. The odds of DBS placement increased across the study period, whereas White patients with PD were 5 times more likely than Black patients to undergo DBS. Individuals, regardless of racial background, with 2 or more comorbidities were 14 times less likely to undergo DBS. Privately insured patients were 1.6 times more likely to undergo DBS. Despite increasing DBS utilization, significant disparities persist in access to DBS. ANN NEUROL 2022;92:246–254
Membrane‐Bound Inward‐Growth of Artificial Cytoskeletons and Their Selective Disassembly
Authors: Xu Qingsong , Li Shanlong , Qi Meiwei , Gao Jing , Chen Chuanshuang , Huang Pei , Wang Yuling , Yu Chunyang , Huang Wei , Zhou Yongfeng
Published: April 2022

The cytoskeleton is one of the most important cellular components. Up to now, most of the reported artificial cytoskeletons are based on a gel‐in‐vesicle strategy. Herein, we report a membrane‐bound inward‐growth pathway to prepare cytoskeleton‐like and radially aligned nanofibers grown from capsule membranes to get membrane‐bound artificial cytoskeletons (MACs). The mechanism therein is disclosed through the direct observation of the intermediates in both dried and liquid states. Furthermore, the as‐prepared MACs show a selective disassembly behavior in the presence of reductants: both capsule membranes and MACs can be disassembled or only MACs can be disassembled through the selective introduction of dynamic disulfide bonds (DS) into them and by the switch of ultraviolet (UV) irradiation. The present work provides a new hierarchical self‐assembly way to construct artificial cytoskeletons with controlled compositions and orientations.
Synthesis and research of basalt microfiber‐reinforced polyurethane elastomer composites
Authors: Wang Danhui , Li Xiaodong , Ge Mengchen , Lei Lisha , Yang Yi , Liu Shuang , Zou Meishuai
Published: April 2022

Basalt microfiber‐reinforced polyurethane elastomer composites (BMF/PUE) were prepared by semi‐prepolymer method in this study. The degree of microphase separation and quantitative analysis of H‐bonding formation in polyurethane were determined by infrared spectroscopy. The fiber surface and the morphology at the tensile fracture interface of the composite materials were observed by scanning electron microscopy. The mechanical properties of composite materials were further measured on an electronic universal testing machine. Dynamic thermomechanical analysis and acoustic impedance tube were used to study the damping and acoustic properties of composite materials, respectively. The results indicated that the composite material prepared by adding 6 g of basalt microfibers treated with 3 min' crushing had the best overall performance. Compared with the matrix, BMF/PUE showed good sound insulation performance with a much wider effective damping temperature range. On the basis of ensuring its excellent overall performance, the mechanical properties were increased by 50.4% in tensile strength, 28.1% in elongation at break, and 14.2% in tear strength.
Interleukin‐13 Receptor α1–Mediated Signaling Regulates Age‐Associated/Autoimmune B Cell Expansion and Lupus Pathogenesis
Authors: Chen Zhu , Flores Castro Danny , Gupta Sanjay , Phalke Swati , Manni Michela , Rivera‐Correa Juan , Jessberger Rolf , Zaghouani Habib , Giannopoulou Eugenia , Pannellini Tania , Pernis Alessandra B.
Published: April 2022

Objective

Age‐associated/autoimmune B cells (ABCs) are an emerging B cell subset with aberrant expansion in systemic lupus erythematosus. ABC generation and differentiation exhibit marked sexual dimorphism, and Toll‐like receptor 7 (TLR‐7) engagement is a key contributor to these sex differences. ABC generation is also controlled by interleukin‐21 (IL‐21) and its interplay with interferon‐γ and IL‐4. This study was undertaken to investigate whether IL‐13 receptor α1 (IL‐13Rα1), an X‐linked receptor that transmits IL‐4/IL‐13 signals, regulates ABCs and lupus pathogenesis.

Methods

Mice lacking DEF‐6 and switch‐associated protein 70 (double‐knockout [DKO]), which preferentially develop lupus in females, were crossed with IL‐13Rα1–knockout mice. IL‐13Rα1–knockout male mice were also crossed with Y chromosome autoimmune accelerator (Yaa) DKO mice, which overexpress TLR‐7 and develop severe disease. ABCs were assessed using flow cytometry and RNA‐Seq. Lupus pathogenesis was evaluated using serologic and histologic analyses.

Results

ABCs expressed higher levels of IL‐13Rα1 than follicular B cells. The absence of IL‐13Rα1 in either DKO female mice or Yaa DKO male mice decreased the accumulation of ABCs, the differentiation of ABCs into plasmablasts, and autoantibody production. Lack of IL‐13Rα1 also prolonged survival and delayed the development of tissue inflammation. IL‐13Rα1 deficiency diminished in vitro generation of ABCs, an effect that, surprisingly, could be observed in response to IL‐21 alone. RNA‐Seq revealed that ABCs lacking IL‐13Rα1 down‐regulated some histologic characteristics of B cells but up‐regulated myeloid markers and proinflammatory mediators.

Conclusion

Our findings indicate a novel role for IL‐13Rα1 in controlling ABC generation and differentiation, suggesting that IL‐13Rα1 contributes to these effects by regulating a subset of IL‐21–mediated signaling events. These results also suggest that X‐linked genes besides TLR7 participate in the regulation of ABCs in lupus.
Super responders: Predicting language gains from JASPER among limited language children with autism spectrum disorder
Authors: Panganiban Jonathan , Kasari Connie
Published: April 2022

Early intervention can provide a great benefit for children with autism spectrum disorder (ASD). However, no single intervention is effective for all children. Even when an intervention is effective overall, individual child response varies. Some children make incredible progress, and others make slow or no progress. Therefore, it is important that the field move towards developing methods to personalize intervention. Operationalizing meaningful change and predicting intervention response are critical steps in designing systematic and personalized early intervention. The present research used improvement in expressive language to group children that received a targeted social communication early intervention, Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER), into super responders and slow responders. Using baseline data from traditional standardized assessments of cognition and behavioral data from validated experimental measures of play and social communication, we used conditional inference tree models to predict responder status. From a sample of 99 preschool age, limited language children with ASD, play diversity was the most significant predictor of responder status. Children that played functionally with a wider variety of toys had increased odds of being a super responder to JASPER. A combination of lower play diversity and impairments in fine motor abilities increased the odds of children being slow responders to JASPER. Results from the present study can inform future efforts to individualize intervention and systematic approaches to augmenting treatment in real time.

Lay Summary

To help us answer the question of for whom an intervention works best, we examined 99 children, age three to five, who qualified as being limited spoken language communicators, and received a targeted intervention for social communication and language. We used child characteristics before intervention to predict which children would improve their language the most and found that the ability to play appropriately with a wider variety of toys predicted the best improvements in expressive language. These findings will help better inform future work to individualize intervention based on the unique needs of each child.
Activists' and social entrepreneurs' approaches towards consumer culture: Providing a protective space for sustainability transitions
Authors: Enthoven Margo P. M. , Thelken Hendrik N.
Published: April 2022

Social entrepreneurs and activists can contribute to sustainability transitions by influencing consumer culture. This can provide a protective space to shelter new sustainability solutions from market pressures until they are ready to scale to the mass market. We study how social entrepreneurs and activists within a sustainable market niche attempt to influence consumer culture. Using grounded theory, we analyse interviews with 26 activists and social entrepreneurs in the market for alternatives to animal products in the Netherlands. We find a synergy where social entrepreneurs' strategies pull consumers into sustainable consumption while activists' strategies focus push consumers out of unsustainable consumption. These strategies contain four tactics: connecting to, showing contrast with and broadening consumers' connection to values associated with sustainable consumerism and a radical innovation tactic. We show how strategies for consumer culture change interact on the niche level of sustainability transitions to create a protective space for sustainability solutions.
Pediatric paranasal sinuses—Development, growth, pathology, & functional endoscopic sinus surgery
Authors: Lee Sophie , Fernandez Justin , Mirjalili S. Ali , Kirkpatrick Joshua
Published: April 2022

The paranasal sinuses (maxillary, frontal, ethmoid, and sphenoid sinuses) are complex anatomical structures. The development and growth of these have been investigated utilizing a number of different methods ranging from cadaveric analysis to modern cross sectional imaging with 3D modeling. An understanding of normal pediatric paranasal sinus embryology and development enables us to better determine when pathology may be affecting the normal developmental process. Cystic fibrosis, chronic sinusitis, deviated nasal septum and cleft lip and palate are some of the conditions which have been shown to effect paranasal sinus development to varying degrees. Functional endoscopic sinus surgery (FESS) is becoming increasingly common and an understanding of sinus anatomy together with when periods of rapid growth occur during childhood is important clinically. Although concerns have been raised regarding the impact of FESS on facial growth, there is limited evidence of this in regards to either changes in anthropomorphic measurements or clinical assessments of symmetry post operatively.
Longitudinal monitoring by next‐generation sequencing of plasma cell‐free DNA in ALK rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors
Authors: Kwon Minsuk , Ku Bo mi , Olsen Steve , Park Sehhoon , Lefterova Martina , Odegaard Justin , Jung Hyun‐Ae , Sun Jong‐Mu , Lee Se‐Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung‐Ju
Published: April 2022

Background

Patients with ALK‐rearranged non‐small cell lung cancer (ALK+ NSCLC) inevitably acquire resistance to ALK inhibitors. Longitudinal monitoring of cell‐free plasma DNA (cfDNA) next‐generation sequencing (NGS) could predict the response and resistance to tyrosine kinase inhibitor (TKI) therapy in ALK+ NSCLC.

Methods

Patients with ALK+ NSCLC determined by standard tissue testing and planned to undergo TKI therapy were prospectively recruited. Plasma was collected at pretreatment, 2 months‐post therapy, and at progression for cfDNA‐NGS analysis, Guardant 360.

Results

Among 92 patients enrolled, circulating tumor DNA (ctDNA) was detected in 69 baseline samples (75%): 43 ALK fusions (62.3%) and two ALK mutations without fusion (2.8%). Two patients showed ALK‐resistance mutations after ceritinib; G1202R, and co‐occurring G1202R and T1151R. Eight patients developed ALK resistance mutations after crizotinib therapy; L1196M (n = 5), G1269A (n = 1), G1202R (n = 1), and co‐occurring F1174L, G1202R, and G1269A (n = 1). Absence of ctDNA at baseline was significantly associated with longer progression‐free survival (PFS; median 36.1 vs. 11.4 months, p = 0.0049) and overall survival (OS; not reached vs. 29.3 months, p = 0.0200). ctDNA clearance at 2 months (n = 29) was associated with significantly longer PFS (25.4 vs. 11.6 months, p = 0.0012) and OS (not reached vs. 26.1 months, p = 0.0307) than those without clearance (n = 22). Patients with co‐occurring TP53 alterations and ALK fusions at baseline (n = 16) showed significantly shorter PFS (7.28 vs. 13.0 months, p = 0.0307) than those without TP53 alterations (n = 25).

Conclusions

cfDNA‐NGS facilitates detection of ALK fusions and resistance mutations, assessment of prognosis, and monitoring dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK‐TKI.
Characterization of 2‐Fluoro‐2’‐deoxyadenosine in Duplex, G‐Quadruplex and i‐Motif
Authors: Hirashima Shingo , Sugiyama Hiroshi , Park Soyoung
Published: April 2022

Among various kinds of fluorine‐substituted biomolecules, 2‐fluoroadenine (2FA) and its derivatives have been actively investigated as therapeutic reagents, radio‐sensitizers, and 19F NMR probes. In spite of their excellent properties, DNA containing 2FA has not been studied well. For fundamental understanding and future applications to the development of functional nucleic acids, we characterized 2FA‐containing oligonucleotides for canonical right‐handed DNA duplex, G‐quadruplex, and i‐motif structures. Properties of 2FA were similar to native adenine due to the small size of the fluorine atom, but it showed unique features caused by high electronegativity. This work provides useful information for future application of 2FA‐modified DNA.
Transition‐Metal‐Free Heterocyclic Carbon‐Boron Bond Formation
Authors: Hazra Subrata , Mahato Somenath , Kanti Das Kanak , Panda Santanu
Published: April 2022

Heteroaryl boronic acids and esters are extremely important and valuable intermediates because of their wide application in the synthesis of marketed drugs and bioactive compounds. Over the last couple of decades, the construction of highly important heteroaryl carbon‐boron bonds has created huge attention. The transition‐metal‐free protocols are more green, less sensitive to air and moisture, and also economically advantageous over the transition‐metal‐based protocols. The transition‐metal‐free C−H borylation of heteroarenes and C−X (X=halogen) borylation of heteroaryl halides represents an excellent approach for their synthesis. Also, various cyclization and alkyne activation protocols have been recently established for their synthesis. The goal of this review article is to summarize the existing literature and the current state of the art for transition‐metal‐free synthesis of heteroaryl boronic acid and esters.
Solid‐Phase Peptide Modification via Deaminative Photochemical Csp3‐Csp3Bond Formation Using Katritzky Salts
Authors: Openy Joseph , Amrahova Gulshan , Chang Jen‐Yao , Noisier Anaïs , Hart Peter ‘t
Published: April 2022

Introduction of unnatural amino acids can significantly improve the binding affinity and stability of peptides. Commercial availability of such amino acids is limited, and their synthesis is a long and tedious process. We here describe a method that allows the functionalization of peptides directly on solid‐support by converting lysine residues to Katritzky salts, and subjecting them to a photochemical Giese reaction under mild reaction conditions. The method avoids the need for amino acid synthesis and instead offers a late‐stage modification route for rapid peptide diversification. While numerous modification approaches at the lysine amine have been described, this work provides the first example of deaminative functionalization of peptides at lysine. The two‐step protocol is compatible with various substrates, lysine analogues, resins, and all proteinogenic amino acids. Finally, by leveraging solid‐phase modification, this protocol facilitates the functionalization of longer peptides as was demonstrated using biologically relevant peptides of up to 15 amino acids.
Copper‐Catalyzed[3 + 2 + 1] Cycloaddition of Alkenes with Benzoquinones and Dicarbonyl Compounds via Tandem Oxidative Dicarbofunctionalization/Cyclization Sequence
Authors: Du Tianxing , Li Song , He Yunfei , Long Huan , Liu Xigong , Li Hai‐Bei , Liu Lei
Published: April 2022

Comprehensive Summary

Developed is an efficient three‐component [3 + 2 + 1] cycloaddition of simple alkenes with two C—H substrates via oxidative dicarbofunctionalization/cyclization sequence. The copper‐catalyzed reaction involves the formation of two C—C bonds and one C—O bond through the cleavage of three C—H bonds in a single operation. The method has an excellent functional group tolerance, and features a broad substrate scope, affording a variety of functionalized chromenes in good yields.
Manganese‐Catalyzed Anti‐Markovnikov Hydroarylation of Enamides: Modular Synthesis of Arylethylamines
Authors: He Yijie , Du Chaoyu , Han Jian , Han Jie , Zhu Chengjian , Xie Jin
Published: April 2022

Comprehensive Summary

The arylethylamine framework is a prevalent motif in a great range of biologically important organic compounds. One intractable task for frontline drug discovery is to find structurally new medicine candidates instead of opioid, based on the construction of a rich chemical space of arylethylamine motif. In this report, a practical protocol for the synthesis of arylethylamine functionality common in pharmaceutical chemicals has been developed. It proceeds by Mn‐catalyzed anti‐Markovnikov hydroarylation of electron‐rich enamides under mild conditions without the use of ligands. In spite of mismatched electronic effects during the manganese‐mediated migratory insertion process, both terminal and internal enamides can be regioselectively hydroarylated with various aryl boronic acids in 15 min. Also, the successful hydroalkenylation of enamides with alkenyl boronic acids in air atmosphere affords an elegant route to synthetically useful β‐alkenylated amines in satisfactory yields. The synthetic robustness and practicality of the reaction reveal its simple operation, short reaction time, viability on a gram‐scale and its value in late‐stage modification of complex molecules.
Get to know your new president
Authors: Hodges Dawn Z.
Published: April 2022

Two of the colleges where I used to work will get new presidents this year. During my career, I welcomed four new presidents. It's always an anxious time because you just don't know what to expect. You hope you'll get a president who will observe, listen, and study life on your campus before making big changes. That's not always the case. One new president I worked for came in like a tornado. She upended life as we knew it and changed the landscape radically.
Non‐invasive evaluation of new‐onset atrial fibrillation after cardiac surgery: a protocol for the BigMap study
Authors: Mork Constantin , Amacher Simon Adrian , Gahl Brigitta , Koechlin Luca , Miazza Jules , Schaeffer Thibault , Schmuelling Lena , Bremerich Jens , Berdajs Denis , Cueni Nadine , Kühne Michael , Mueller Christian , Osswald Stefan , Reuthebuch Oliver , Schurr Ulrich , Sticherling Christian , Kopp Lugli Andrea , Marsch Stephan , Pargger Hans , Siegemund Martin , Eckstein Friedrich , Hollinger Alexa , Santer David
Published: April 2022

Aims

New‐onset atrial fibrillation (NOAF) is the most common complication after cardiac surgery, occurring in 25–50% of patients. It is associated with post‐operative stroke, increased mortality, prolonged hospital length of stay, and higher treatment costs. Previous small observational studies have identified the left atrium as a source of the electrical rotors and foci maintaining NOAF, but confirmation by a large prospective clinical study is still missing. The aim of the proposed study is to investigate whether the source of NOAF lies in the left atrium. The correct identification of NOAF‐maintaining structures in cardiac surgical patients might offer potential therapeutic targets for prophylactic perioperative ablation strategies.

Methods and results

This is a prospective single‐centre observational study of patients developing NOAF after cardiac surgery. The primary outcome is the description of NOAF‐maintaining structures within the atria. Key secondary outcomes include overall mortality, intensive care unit length of stay, hospital–ventilator‐free days, and proportion of persistent NOAF. In NOAF patients, the non‐invasive electrophysiological mapping will be conducted using a 252‐electrode electrocardiogram vest. After mapping, a low‐dose computed tomography scan of the chest will be performed to integrate the electrophysiological mapping results into a 3D picture of the heart. The study will include approximately 570 patients, of whom 30% (n = 170) are expected to develop NOAF. Sample size calculation revealed that 157 NOAF patients are necessary to assess the primary outcome. Patients will be tracked for a total of 5 years.

Conclusions

This is the largest prospective study to date describing the electrophysiological mechanisms of NOAF using non‐invasive mapping.
The predictive value of self‐compassion for psychological adjustment in left ventricular assist device patients: an observational study
Authors: Morgenroth Olaf , Petersen Lars‐Eric , Frey Norbert , Reinecke Alexander
Published: April 2022

Aims

Implantation of a left ventricular assist device (LVAD) is an established treatment option for patients with advanced heart failure. However, apart from its challenging medical management, it comes with serious psychological implications. Empirical evidence suggests that self‐compassion, a self‐regulation strategy for countering negative self‐directed emotions, might be a promising approach in facilitating psychological adjustment also in LVAD patients. The aims of the present study were to investigate self‐compassion as a protective factor for anxiety and depressive symptoms, to test whether taking a decentred perspective mediates these effects, and to explore whether self‐compassion predicts the clinically rated functional health status.

Method and results

A sample of N = 45 patients (36 male) with a mean age of 60.5 years (SD = 10.8) from the outpatient department for terminal heart failure at the University Medical Center in Kiel, Germany, participated in the study. Patients completed self‐report measures for psychological adjustment (HADS), self‐compassion (SCS), and decentring (EQ). Functional health status was determined by the NYHA classification. The more patients were self‐compassionate, the less they reported anxiety (r = −0.28) and depressive symptoms (r = −0.34). Decentring mediated both effects. Moreover, self‐compassion predicted the functional health status, even when controlling for anxiety (odds ratio [OR] = 0.09) and depressive symptoms (OR = 0.11).

Conclusions

This study provides the first evidence for a significant interrelation between self‐compassion and common adverse psychological conditions in LVAD patients. Longitudinal data and the evaluation of interventions to strengthen self‐compassion are needed to further validate the beneficial effects of self‐compassion in LVAD patients in the future.
A Green New Balance: Interactions among riparian vegetation plant traits and morphodynamics in alluvial rivers
Authors: Bywater‐Reyes Sharon , Diehl Rebecca M. , Wilcox Andrew C. , Stella John C. , Kui Li
Published: April 2022

The strength of interactions between plants and river processes is mediated by plant traits and fluvial conditions, including above‐ground biomass, stem density and flexibility, channel and bed‐material properties, and flow and sediment regimes. In many rivers, concurrent changes in (1) the composition of riparian vegetation communities as a result of exotic species invasion and (2) shifts in hydrology have altered physical and ecological conditions in a manner that has been mediated by feedbacks between vegetation and morphodynamic processes. We review how Tamarix, which has invaded many southwestern US waterways, and Populus species, woody pioneer trees that are native to the region, differentially affect hydraulics, sediment transport, and river morphology. We draw on flume, field, and modelling approaches spanning the individual seedling to river‐corridor scales. In a flume study, we found that differences in the crown morphology, stem density, and flexibility of Tamarix compared to Populus influenced near‐bed flow velocities in a manner that favoured aggradation associated with Tamarix. Similarly, at the patch and corridor scales, observations confirmed increased aggradation with increased vegetation density. Furthermore, long‐term channel adjustments were different for Tamarix‐ versus Populus‐dominated reaches, with faster and greater geomorphic adjustments for Tamarix. Collectively, our studies show how plant‐trait differences between Tamarix and Populus, from individual seedlings to larger spatial and temporal scales, influence the co‐adjustment of rivers and riparian plant communities. These findings provide a basis for predicting changes in alluvial riverine systems which we conceptualize as a Green New Balance model that considers how channels may adjust to changes in plant traits and community structure, in addition to alterations in flow and sediment supply. We offer suggestions regarding how the Green New Balance can be used in management and invasive species management.
Health monitoring jeopardy prophylaxis model based on machine learning in fog computing
Authors: Suggala Ravi Kumar , Krishna M. Vamsi , Swain Sangram Keshari
Published: April 2022

Cloud‐based fog computing was developed in recent years to make it easier for patients to monitor distant health and discover mosquito‐borne syndromes at an initial period, allowing to track the mosquito‐borne illnesses. Many obstacles have been confronted by the technology, including high latency, mobility, overhead connectivity, and location consciousness. Due to the security issue and wrong prediction of the diseases, users are affected by getting wrong alert messages from fog which increase the disease spreading. Hence a novel Prevention Technique based on Fog Computing has been introduced to prevent the epidemic syndrome at an initial period and safeguard the people around the world. Initially, each user register their personal information in Pristine Database through IoT device. These information are encrypted with 16 round of key‐dependent operation via new Blowfish Encryption Algorithm. Subsequently, the mosquito spawned disease is diagnosed by measuring the resemblance factor between the user and disease through the Hybrid Endemic Halsen Classifier and the Resemblance Coefficient are used to diagnose and categorize users as infected or unaffected. The mosquito‐borne disease is detected using this method by assessing the similarity factor between the user and the disease with less computing time. As a result, if a new symptom is found rather than one from the given medical dataset, the information will be saved in the Pristine Database, and the classification process will be faster with less computing time in the future if the same symptom is identified. Finally, the novel Temporal Social Network Analysis was developed to assess the likelihood of a disease breakout also analyze the infected users and send the awareness message to take the precautionary measures in the cloud processing layer. Thus, the proposed work effectively predicts and prevents the spreading of epidemic outbreaks with accuracy of 97% which is 7.2% higher than the existing approaches, and reduced latency of 0.18 second.
Vitamin D ameliorates asthma‐induced lung injury by regulating HIF‐1α/Notch1 signaling during autophagy
Authors: Huang Chaowen , Peng Ming , Tong Jinzhai , Zhong Xueying , Xian Jun , Zhong Liandi , Deng Jiongrui , Huang Yanming
Published: April 2022

Herein, we aimed to determine the effect of vitamin D (Vit D) and underlying mechanisms on asthma‐induced lung injury via regulation of HIF‐1α/Notch1 (hypoxia‐inducible factor 1 alpha/neurogenic locus notch homolog protein 1) signaling during autophagy. We established an asthma mouse model using respiratory syncytial virus (RSV) nasal drop combined with ovalbumin (OVA) atomization. Mice were treated with different Vit D concentrations. Pathological changes and cell apoptosis were examined using hematoxylin–eosin (HE) staining and TUNEL (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate (dUTP) nick end‐labeling) assay, respectively. Additionally, periodic acid–Schiff (PAS) and Masson's trichrome staining solutions were used to examine changes in lung tissue. Immunofluorescence determined LC 3B (microtubule‐associated protein 1 light chain 3B) expression in lung tissues, whereas western blotting and immunohistochemistry were used to evaluate other proteins, including HIF‐1α and Notch1. Compared with the normal group, the asthma model group exhibited pathological lung tissue deterioration, elevated fibrosis, increased apoptosis cell numbers, and upregulated autophagy. Vitamin D supplementation ameliorated pathological changes and fibrosis in the lung tissue. Furthermore, Vit D treatment significantly suppressed apoptotic cell numbers and autophagy while enhancing the HIF‐1α/Notch1 pathway. Given the HIF‐1α/Notch1 agonistic activity, Vit D treatment inhibited apoptosis cell numbers, which were increased following asthma‐induced upregulation of autophagy. Vitamin D improved asthma‐induced lung tissue injury by suppressing autophagy via regulation of HIF‐1α/Notch1 signaling in vivo.
Exploring polygenic‐environment and residual‐environment interactions for depressive symptoms within the UK Biobank
Authors: Gillett Alexandra C. , Jermy Bradley S. , Lee Sang Hong , Pain Oliver , Howard David M. , Hagenaars Saskia P. , Hanscombe Ken B. , Coleman Jonathan R. I. , Lewis Cathryn M.
Published: April 2022

Substantial advances have been made in identifying genetic contributions to depression, but little is known about how the effect of genes can be modulated by the environment, creating a gene–environment interaction. Using multivariate reaction norm models (MRNMs) within the UK Biobank (N = 61294–91644), we investigate whether the polygenic and residual variance components of depressive symptoms are modulated by 17 a priori selected covariate traits—12 environmental variables and 5 biomarkers. MRNMs, a mixed‐effects modelling approach, provide unbiased polygenic–covariate interaction estimates for a quantitative trait by controlling for outcome‐covariate correlations and residual–covariate interactions. A continuous depressive symptom variable was the outcome in 17 MRNMs—one for each covariate trait. Each MRNM had a fixed‐effects model (fixed effects included the covariate trait, demographic variables, and principal components) and a random effects model (where polygenic–covariate and residual–covariate interactions are modelled). Of the 17 selected covariates, 11 significantly modulate deviations in depressive symptoms through the modelled interactions, but no single interaction explains a large proportion of phenotypic variation. Results are dominated by residual–covariate interactions, suggesting that covariate traits (including neuroticism, childhood trauma, and BMI) typically interact with unmodelled variables, rather than a genome‐wide polygenic component, to influence depressive symptoms. Only average sleep duration has a polygenic–covariate interaction explaining a demonstrably nonzero proportion of the variability in depressive symptoms. This effect is small, accounting for only 1.22% (95% confidence interval: [0.54, 1.89]) of variation. The presence of an interaction highlights a specific focus for intervention, but the negative results here indicate a limited contribution from polygenic–environment interactions.
Microfacies and depositional environment of Tarbur Formation (Upper Cretaceous‐Lower Palaeocene) Zagros area, southwestern Iran
Authors: Afghah Massih
Published: April 2022

Over 3,000 m of Upper Cretaceous‐Lower Palaeocene sediments belonging to the Tarbur Formation were studied in seven stratigraphic sections around Shiraz city (south Zagros Basin, SW of Iran). The Tarbur Formation is divided into two informal lithostratigraphic units: a lower well‐bedded rudist limestone and an upper massive rudist limestone. Both units comprise rudist particles as a major organo‐detrital component. Microscopic studies have identified the presence of the following carbonate microfacies types in the Tarbur Formation: rudist orbitoid wackestone, miliolid algal‐bioclast wackestone, rudist packstone, rudist orbitoid packstone, rudist intraclast miliolid packstone, rudist‐agglutinated foraminifer grainstone, orbitoid rudist grainstone, rudist‐hyaline foraminifer‐intraclast grainstone, rudist boundstone and coral boundstone, which are attributed to shallow water lagoon, bar and fore‐reef palaeoenvironments. The rudist fragments co‐existed with a Campanian/Maastrichtian foraminiferal assemblage. The stratigraphic distribution of the investigated microfacies was affected by vertical displacement of studied area basement faults.
The effects of dietary fiber on common complications in critically ill patients; with a special focus on viral infections; a systematic reveiw
Authors: Hajipour Azadeh , Afsharfar Maryam , Jonoush Mona , Ahmadzadeh Mina , Gholamalizadeh Maryam , Hassanpour Ardekanizadeh Naeemeh , Doaei Saeid , Mohammadi‐Nasrabadi Fatemeh
Published: April 2022

Background

Viral infections are mostly highly contagious and may cause widespread health problems. Some studies reported that the dietary fiber (DF) may be effective in reducing the complications of viral infections in intensive care unit (ICU) patients. The present review study aimed to investigate the effect of DF on common complications in critically ill patients with viral infections.

Methods

A literature review was conducted for the published papers in English from January 2001 to July 2021 using related keywords. Studies with clinical trial or case‐control design described the effects of fiber intake on the complications of viral infections in patients admitted to the ICU were collected.

Results

DF may reduce the mortality rate of viral infections through modulating inflammatory processes. A higher intake of DF intake may improve hyperglycemia and impaired glucose tolerance in patients with viral infections. A high‐fiber formula in enteral nutrition was reported to reduce the risk of diarrhea in patients with viral infections.

Conclusion

DF may reduce the complications of viral infections such as inflammation, diarrhea, hyperglycemia, and mortality in critically ill patients. Future longitudinal studies on the amount and type of DF are warranted.
Does subjective well‐being matter when assessing the impacts of irrigation infrastructure? Empirical evidence from Madhya Pradesh, India
Authors: Sinha Ranu , Dadson Simon , Hope Robert
Published: April 2022

Investments to rehabilitate irrigation infrastructure aim to enhance climate resilience and improve farmers' livelihoods in the face of hydrological risks. Studies seeking to assess the impacts from investments in irrigation primarily focus on yield and income‐related poverty measures. This approach provides an incomplete picture of the distributional implications of investments, such as the impact of rehabilitated irrigation infrastructure on the subjective well‐being of farmers. Drawing on data from 707 farmers in Madhya Pradesh, India, we explore whether investments to rehabilitate irrigation infrastructure are associated with changes in subjective well‐being among smallholders. Our findings show a positive relationship between farmers with access to rehabilitated surface irrigation and well‐being improvements. Results reveal that farmers in areas with rehabilitated irrigation canals experience improvements in subjective well‐being which are 20%–30% higher in comparison to farmers in areas without rehabilitated canals. When results are disaggregated, we find a larger positive effect on well‐being for farmers in deficient‐rainfall areas compared to average‐ or high‐rainfall areas. The integration of contextual factors related to subjective well‐being into future assessments of infrastructure investments in India can enhance knowledge of the multidimensional benefits of canal irrigation among diverse farming groups facing differing degrees of hydrological risk.
Preparing pharmacy trainees for a future in research and contributing to the medical literature
Authors: Lichvar Alicia B. , Smith Condeni Melanie , Pierce Dana R.
Published: April 2022

Clinical research is a skill that can be honed and cultivated in the right educational environment. Creating experiences to maximize growth and interest in clinical research can occur both during pharmacy school and throughout postgraduate training. The purpose of this “how‐to” guide is to assist pharmacists, as well as their students and residents, with effectively structuring experiences and programs that instill and cultivate a lifelong desire to contribute to the medical literature. The overarching areas of focus are threefold: (1) identifying trainees and mentors, (2) crafting research training experiences, and (3) supporting continued interest and growth in research after completion of the initial experience. Early introduction of a positive research culture in the trainee experience through structured and thoughtful curricula and experiences can maximize learner potential. Several thoughtful steps and recommendations can maximize these experiences and opportunities for learners and new practitioners. Instilling and cultivating a lifelong desire to contribute to the medical literature in pharmacy trainees remains a challenge that is both worthy and necessary to pursue for the sakes of our profession, patients, and trainees.
Evaluation of burnout among emergency medicine pharmacists
Authors: Rozycki Elizabeth , Bilhimer Matthew , Bridgeman Patrick , Slocum Giles W. , Cocchio Craig , Weant Kyle , Groth Meghan , Sturgill Marc , Shirk Mary Beth , Li Junan , Acquisto Nicole M.
Published: April 2022

Introduction

Burnout syndrome is a prolonged response to chronic emotional and interpersonal stressors and is becoming an increasing concern in the medical community. Burnout in emergency medicine (EM) pharmacists has not been previously assessed.

Objectives

To identify the prevalence of burnout among EM pharmacists, in addition to demographic, professional, seasonal, and job‐related associations.

Methods

Pharmacists practicing greater than 50% of their time in the emergency department (ED) setting were invited through the American College of Clinical Pharmacy Emergency Medicine Practice and Research Network listserv to complete a survey at three separate, 4‐week, time periods (July 2018, October 2018, and April 2019). The survey contained the Maslach Burnout Inventory for Medical Personnel to detect burnout. Questions regarding personal and job‐specific demographics were asked. Descriptive statistics were used to report demographics and burnout dimensions in each period. Spearman's rank correlation and univariate and multivariate analyses were performed to identify predictors of burnout and potential associations.

Results

A total of 485 surveys were completed across all periods (116 [July], 207 [October], 162 [April]) and response rates were 18.4%, 31.6%, and 22.7%, respectively. Burnout was identified in 69.8%, 67.1%, and 68.5% of respondents with no difference between periods. A majority of participants had high depersonalization scores (50.6‐76.3%) during the three survey periods.

Younger age, more ED visits per year, level I trauma center designation, and lower percentage of direct patient care time were associated with increased odds of burnout in the July 2018 period. Intent to leave one's current position or the specialty of EM and consideration of a job with different hours had positive correlations with burnout.

Conclusions

Burnout is prevalent in a majority of EM pharmacists throughout the year. It is difficult to identify exact predictors of burnout; however, potential contributors include age, trauma center designation, patient volumes, and direct patient care time.
Surveying the selection landscape: A systematic review of processes for selecting postgraduate year 1 pharmacy residents and key implications
Authors: Reed Brent N. , Noel Zachary R. , Heil Emily L. , Shipper Andrea G. , Gardner Aimee K.
Published: April 2022

Introduction

The growth in applicants to postgraduate year one (PGY1) pharmacy residency programs outpaces the number of available positions, requiring that residency program directors (RPDs) evaluate an increasing number of qualified candidates. Discrepancies exist in the characteristics thought to distinguish exemplary candidates and the methods for selecting them.

Objectives

To characterize the burdens of the selection process, summarize methods for selecting PGY1 residents based on a systematic review, and list best practices for improving the process.

Methods

Burdens were characterized by collecting applicant costs via survey and program costs and workload estimates via interviews of RPDs at small, medium, and large programs. For the systematic review, a medical librarian searched for articles pertaining to resident selection. Articles underwent a title/abstract screen and full text screen by two authors and a third served as tiebreaker. Data were summarized in descriptive form, and consisted of study methodology, selection method(s) of interest, and principal findings.

Results

The median cost to applicants was $1756 (interquartile range [IQR] $1271‐$2423). The median cost to residency programs was $5068 (IQR $3943‐$12 310). Program directors spent a median of 56.5 hours on selection; a median of 22.0 and 21.3 hours were spent by each preceptor and current resident, respectively. A total of 51 articles (22 surveys and 29 other designs) were included in the systematic review. Biographical data, interviews, and references were among the most commonly explored evaluation methods. Articles consisted primarily of descriptions of selection methods, summaries of RPD attitudes regarding these methods or characteristics desired in a resident, or factors that predicted a successful match. Few articles investigated the validity and reliability of selection methods.

Conclusion

Selection is a cumbersome process for both applicants and programs alike. Fortunately, numerous opportunities exist to improve the process, and these should serve as the basis of future research.
Expanding pharmacy resident research capacity through integration of introductory pharmacy practice experience students into a prospective research study: A novel application of the layered learning practice model
Authors: Rashidi Sanam , Shieh Jennifer , Agustin Janelle , Gross A. Kendall , Thompson Ashley E. , Li Fanny , Staub Elizabeth S.
Published: April 2022

Introduction

Research and quality improvement projects are routine in contemporary pharmacy practice and are valuable components of experiential training for pharmacy students. There are descriptions of the layered learning practice model (LLPM) for expanding direct patient care activities, but its application in clinical research has not been described in the literature.

Objectives

This case study provides a description of the novel integration of introductory pharmacy practice experience (IPPE) students into a prospective research study led by a pharmacy resident to expand screening, enrollment, and data collection capacity.

Methods

IPPE students were integrated into a prospective, observational study evaluating the effect of time to restart of prior to admission psychotropic medications on the development of intensive care unit (ICU) delirium. Using the LLPM, attending pharmacist preceptors mentored the pharmacy resident, who then assumed the primary preceptor role for three IPPE students. Students were integrated into project activities including institutional review board submission, data collection, and data analysis. Study data were collected and managed using Research Electronic Data Capture (REDcap). Student contributions to longitudinal research activities were quantified using descriptive statistics.

Results

There were 487 patients screened for study enrollment, and 112 patients were included in the study. Research team members completed 890 ICU delirium screenings using the Confusion Assessment Method for the ICU (CAM‐ICU) tool and inputted 243 prospective medication reconciliations. Collectively, the students, resident, and pharmacist preceptors completed 48.6%, 38.7%, and 12.7% of CAM‐ICU assessments, respectively. This study was associated with increased opportunities for pharmacy resident‐led and student‐led scholarly activities.

Conclusion

The integration of IPPE students into a prospective research study was successful in using the LLPM in expanding resident research capacity while being mutually beneficial to the pharmacy students and residents.
Pharmacist intervention and anti‐platelet medication monitoring in patients following stroke and transient ischemic attack
Authors: Greger Jessica , Wojcik Rachael , Westphal Erica , Aladeen Traci , Landolf Kaitlin , Boyce Samantha , Rainka Michelle , Gengo Fran , Bates Vernice
Published: April 2022

Introduction

Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do not demonstrate optimal antiplatelet effects from these therapies.

Objectives

The primary objective of this study was to determine if pharmacist medication intervention paired with anti‐platelet medication monitoring with whole blood aggregometry improved responsiveness to antiplatelet treatment when compared with standard‐of‐care, alone in patients at risk of recurrent stroke or transient ischemic attack (TIA).

Methods

This retrospective chart review at an outpatient neurology practice examined patients treated post‐stroke or post‐TIA between 2005 and 2017. Patients were categorized as either having undergone platelet function testing (PFT) with pharmacist intervention and standard‐of‐care or standard‐of‐care alone. Patient populations for each group were matched based on age, sex, and ABCD2 risk scores. Pharmacotherapeutic management and interventions were assessed in each group.

Results

A total of 342 patients were included as two matched groups (n = 171 for each group) with parallel baseline characteristics. Drug‐drug interactions were identified (P < .0001), and counseling on adherence (P = .0008) occurred statistically significantly more often with a pharmacist involved in patient care. After pharmacist intervention and PFT, 83% of patients were considered responsive to their antiplatelet therapy compared with 27% at baseline in the pharmacist intervention group (P < .0001).

Conclusion

Pharmacist interventions optimized secondary stroke/TIA prophylaxis therapy, decreased drug‐drug interactions, and increased adherence counseling. Patients who underwent PFT and pharmacist intervention transitioned from nonresponsive to responsive to their antiplatelet therapy regimen.