bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case–control study in Tianjin, China
Authors: Li Peiying , Yang Qiaoyun , Li Yao , Han Yu , Qu Zhiyi , Gao Lei , Cui Tingkai , Xiong Wenjuan , Xi Wei , Zhang Xin
Published: August 2022

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case–control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy‐PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy‐PAHs were statistically significantly higher in the ASD group, with the exception of 2‐hydroxynaphthalene (2‐OHNap) and 4‐hydroxyphenanthrene (4‐OHPhe). Moreover, urinary hydroxy‐PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1‐hydroxynaphthalene (1‐OHNap, β = 3.32), hydroxyphenanthrenes (1/2/3 + 9‐OHPhes, β = 3.41–5.12), 1‐hydroxypyrene (1‐OH‐Pyr; β = 3.91), 2‐hydroxybenzofuran (2‐OHDBF; β = 3.93), and ∑OH‐PAHs (β = 4.67) were positively associated with CARS scores after adjusting for covariates (all p < 0.05). When applying the ABC scale, 1‐OHPyr levels were positively associated with ABC total scores (β = 18.54), with the strongest associations evidenced in regard to the social relatedness (β = 6.51) and language domains (β = 6.51) (all p < 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1‐OHNap, 1‐OHPhe, and 3 + 9‐OHPhe levels in regard to CARS scores, and for 1‐OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy‐PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism.

Lay summary

We conducted an epidemiologic study evaluating the associations of urinary hydroxy‐PAH levels with autism spectrum disorder (ASD), autism symptomology, and autistic behaviors. We found that urinary hydroxy‐PAHs were statistically significantly associated with ASD. We note strong statistically significant associations between 1‐OHNap, 1‐OHPhe, and 3 + 9‐OHPhe levels and increased severity of autism symptomology, as well as a strong statistically significant association between 1‐OHPyr levels and behavioral characteristics within the social and linguistic domains. This work, if confirmed, will contribute to the future development of diagnostics for children with mild autism, as well as to environmental measures to promote the health and wellbeing of children with autism spectrum disorders.
Development and validation of a liquid chromatography coupled with tandem mass spectrometry method for determining total and unbound pamiparib in human plasma and brain tumors
Authors: Jiang Jun , Bao Xun , Yue Yang , Schiff David , Bindra Ranjit , Li Jing
Published: August 2022

Pamiparib (BGB‐290) is an orally bioavailable, small molecule inhibitor of poly (ADP‐ribose) polymerase 1 (PARP1) and PARP2. A reversed‐phase LC with tandem mass spectrometry method was developed and fully validated for determining total and unbound pamiparib concentrations in human plasma and brain tumor tissue. Plasma and tissue homogenate samples were prepared by methanol protein precipitation. Pamiparib and the internal standard [13C2,15N2]pamiparib were separated on a Waters BEH C18 (50 × 2.1 mm, 1.7 μm) column, with a gradient elution consisting of mobile phases A (0.1% formic acid in water) and B (0.1% formic acid in acetonitrile) at a flow rate of 0.25 mL/min. The analytes were monitored with multiple reaction monitoring mode under positive electrospray ionization. The method was fully validated for specificity, linearity, accuracy and precision, matrix effect and recovery, and short‐ and long‐term stability. The lower limit of quantitation was 0.5 nM of pamiparib in plasma or tissue homogenate. The calibration curve was linear over the pamiparib concentration range of 0.5–1000 nM in plasma. The intra‐ and inter‐day precision and accuracy were within the generally accepted criteria for bioanalytical method. Pamiparib was stable in plasma at −80°C for at least 6 months. The method was successfully applied to assess the plasma and tumor pharmacokinetics of total and unbound pamiparib in patients with glioma.
Neuropsychiatric Inventory domains cluster into neuropsychiatric syndromes in Alzheimer's disease: A systematic review and meta‐analysis
Authors: Hiu Shaun Kuan Wei , Bigirumurame Theophile , Kunonga Patience , Bryant Andrew , Pillai Manjunadh
Published: August 2022

Background: Studies of patients with Alzheimer's disease (AD) have observed that neuropsychiatric symptoms (NPS) tend to co‐occur as neuropsychiatric syndromes and have generally shown mixed results regarding the number and composition of syndromes. We systematically reviewed how neuropsychiatric syndromes in AD have been defined and compared the different published definitions in a pooled sample of AD patients using meta‐analytic structural equation modeling (MASEM).

Methods: Studies examining the factor structure of the Neuropsychiatric Inventory (NPI) and published from 1994 to 2021 were included. We contacted the corresponding authors of eligible studies for correlation coefficients between NPI items. We pooled correlations under a random effects MASEM model and fitted and compared measurement models from published studies to identify a best‐fitting model.

Results: Twenty‐five studies were included in the systematic review, and correlations were obtained from seven studies for MASEM. For the NPI‐10 (seven studies, n = 5185), a five‐factor structure was found to have a good fit to the data. For the NPI‐12 (four studies, n = 2397), we were unable to identify a factor structure that displayed a good model fit.

Conclusion: This systematic review and meta‐analysis contribute to the development of a theoretical model of neuropsychiatric syndromes in AD and reveals the barriers that accompany MASEM methodology.
Genotype–phenotype characteristics of Vietnamese patients diagnosed with Charcot–Marie–Tooth disease
Authors: Nguyen‐Le Trung‐Hieu , Do Minh Duc , Le Linh Hoang Gia , Nhat Quynh Nhu Nguyen , Hoang Nghia Trong Tien , Van Le Tuan , Mai Thao Phuong
Published: August 2022

Background

Charcot–Marie‐Tooth (CMT) disease is one of the most common hereditary neuropathies. Identifying causative mutations in CMT is essential as it provides important information for genetic diagnosis and counseling. However, genetic information of Vietnamese patients diagnosed with CMT is currently not available.

Methods

In this study, we described the clinical profile and determined the mutation spectrum of CMT in a cohort of Vietnamese patients with CMT by using a combination of multiplex ligation‐dependent probe amplification and next‐generation sequencing targeting 11 genes PMP22, MPZ, EGR2, NEFL, MFN2, GDAP1, GARS, MTMR2, GJB1, RAB7A, LITAF.

Results

In 31 CMT cases, the mutation detection rate was 42% and the most common genetic aberration was PMP22 duplication. The pedigree analysis showed two de novo mutations c.64C > A (p.P22T) and c.281delG (p.G94Afs*17) in the NEFL and PMP22 genes, respectively.

Conclusion

The results of this study once again emphasize the important role of molecular diagnosis and provide preliminary genetic data on Vietnamese patients with CMT.
Nanostructured anatase TiO2 as anode of high‐performance lithium‐ion batteries
Authors: Paul Sourav , Rahman Md. Arafat , Islam Md. Saiful , Islam Md. Rasidul , Siddiqui Safina‐E‐Tahura
Published: August 2022

Nanostructured anatase TiO2 (NSA‐TiO2) was synthesized via electrochemical anodization of pure Ti foils in a fluorine‐containing electrolyte. The synergistic effects of the anodization period (1 and 2 h) and the surface condition of Ti foils (scratched and unscratched) before anodization was investigated. Four nanostructure variants—unscratched 1 h, unscratched 2 h, scratched 1 h, and scratched 2 h with average pore diameters 15 ± 7.4, 10.1 ± 8.5, 7 ± 7.12, and 8.1 ± 3.79 nm, respectively, were fabricated to assess as negative electrodes of high‐performance lithium‐ion batteries (LIBs). The corresponding first cycle discharge capacities of as‐synthesized NSA‐TiO2 exhibited 433, 93.33, 453.33, and 460.0 mAhg−1. LIB with scratched 1 h NSA‐TiO2 as anode exhibited very propitious outcomes. The reversible capacity at a high 1 C current rate was displayed as 100 mAhg−1 even after 400 cycles along with 103.27% coulombic efficiency. The superior electrochemical performances are attributed to its high specific surface area due to its nanoporous structure. These nanoporous structures provide higher contact between electrodes and electrolytes, shortening the diffusion pathways for conductive ions and electrons that ensured faster kinetics. However, scratching operations increased surface area in the final nanostructure while the short anodization period substantially increased the number of pores.
Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer
Authors: Zhao Jing , Zhuo Xiaoli , Liu Lei , Yang Zhe , Fu Guobin
Published: August 2022

Small‐cell lung cancer (SCLC) accounts for 15%–20% of primary lung cancers, and it is characterized by low differentiation, rapid proliferation, and early metastasis. At least two‐thirds of SCLC patients present with the extensive stage (ES) at the time of initial clinical diagnosis. Over the last 2 decades, platinum‐based combination chemotherapy has remained the standard first‐line treatment for SCLC. With the introduction of the immunotherapy era, immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first‐line treatment option for ES‐SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines. Therefore, in this review, we present the latest research advances in SCLC treatment, predictive biomarkers, and other topics of high interest to provide options for patients with SCLC.
Treating pediatric hoarding behaviors with an exposure response prevention model: A case study
Authors: Gardiner Kristen , Herren Jennifer , Freeman Jennifer , O'Connor Erin
Published: August 2022

With TV shows such as Hoarding buried alive, mainstream media depictions of hoarding disorder are presented mostly in the context of adults. Interestingly, however, studies have found that the onset of hoarding disorder often occurs in childhood between the ages of 8 and 10 (Morris et al., 2016). Since hoarding can onset at a young age, early intervention could help decrease the long‐term impairment of the disorder. According to the Diagnostic and statistical manual of mental disorders hoarding disorder is characterized as tending to collect items, difficulty in throwing items away despite the items' value or significance, and possessing an excessive number of items, leading to clutter (5th ed.; DSM–5; American Psychiatric Association, 2013). Despite a typical onset in childhood, most hoarding treatment and research has focused on adults because hoarding behaviors in youth can be challenging to identify due to family accommodation (Morris et al., 2016). In this article, we will review the prevalence of pediatric hoarding and provide a case example to describe clinical considerations for treating pediatric hoarding with exposure with response prevention (ERP).
School shootings: Advocacy and education as prevention
Authors: Walters Anne S.
Published: August 2022

Perhaps the school shooting in Uvalde, Texas in May of 2022 will lead to lasting change with the signing of the bipartisan gun bill on June 26 by President Biden. Though not as far reaching as some hoped it would be — it does extend requirements for background checks for prospective buyers under the age of 21, funds increases in mental health and drug courts to carry out red flag laws and confiscate guns, funds increases in school safety, toughens laws against trafficking of guns, and includes recent partners in the ban on domestic abusers purchasing firearms. These are positive steps.
Social, health and ethnicity correlates of complaints of excessive police force
Authors: Smith Sven , Ferguson Christopher J. , San Miguel Claudia E. , Ynalvez Marcus Antonius , Henderson Howard
Published: August 2022

Background

Following several high‐profile police shootings of Black Americans, renewed debate has focused on race as a predictor of police violence. Past research has been inconsistent on this score. Some scholars argue that socioeconomic issues are better predictors of police‐related violence than are race and ethnicity.

Aims

To test relationships between complaints of excessive use of police violence and racial/ethnic population demographics, allowing for social and mental health variables.

Methods

We examined records from all 195 municipal police departments in California to identify complaints of excessive force by police and tested for associations between such complaints and health, socio‐economic and demographic data from county records, using multivariate analyses.

Results

There was no difference in reporting between communities according to Black or White American residency proportions; communities with more Latino Americans were less likely to complain formally of excessive use of police force. The strongest associate of complaints to police departments that their employees had used excessive force was experiencing mental distress in the community.

Conclusions

Our findings are limited by reliance on complaints to police authorities rather than actual incidence of police use of excessive force and by having to map municipal data on to county data, but the finding that factors other than or in addition to any inherent police problems may contribute to excessive use of force by the police offers new lines for remedying the problem. In particular, our findings suggest that more training for police in recognising and managing mental distress and more provision of mental health experts to work alongside police would be worth evaluating as a next step.
Calcinosis of the internal jugular vein: Interesting presentation of tertiary hyperparathyroidism
Authors: Shires Courtney B. , Shete Mona
Published: August 2022

Tumoral calcinosis is a severe complication of hemodialysis. A 49‐year‐old male on dialysis for end‐stage renal disease developed a large calcified retropharyngeal mass. This caused stridor and dyspnea, necessitating an emergency awake tracheostomy. This is the first report of internal jugular vein calcinosis. Surgery is recommended.
Coronavirus disease 19 (COVID‐19) and Cerebral venous sinus thrombosis (CVST): A case series and review of the literature
Authors: Kallel Nesrine , Saidani Amal , Kotti Amina , Moussa Nedia , Maddeh Sabrine , Gargouri Rahma , Msaad Sameh , Feki Walid
Published: August 2022

A large proportion of patients with coronavirus disease 19 (COVID‐19) suffer from excessive coagulation activation and coagulopathy which predisposes them to a wide spectrum of thrombotic events including in situ pulmonary thrombosis, deep‐vein thrombosis, and associated pulmonary embolism, as well as arterial thrombotic events. Cerebral venous sinus thrombosis (CVST) have also been reported but in a very small number of cases. This report aims to increase awareness about CVST as a potential neurological thromboembolic complication in patients with coronavirus disease. We report three COVID‐19 patients presenting with CVTS. We also review all previously described cases and present an overview of their demographic, clinical, and diagnostic data. We describe three patients with concomitant coronavirus disease and CVST among 1000 hospitalized COVID‐19 patients (2 males, 1female, and mean age of 37 years). One patient was previously healthy, while the two others had a history of chronic anemia and ulcerative colitis, respectively. CVST symptoms including seizure in two patients and headache in one patient occurred day to weeks after the onset of COVID‐19 symptoms. Three months of anticoagulant therapy was given for all three patients with favorable outcomes. No neurological sequelae and no recurrence occurred within 6 months after hospital discharge. Our search identified 33 cases of COVID‐19 complicated by CVST. The mean age was 45.3 years, there was a slight male predominance (60%), and more than half of cases were diagnosed in previously healthy individuals. All cases of CVT were clinically symptomatic and were observed in patients with a different spectrum of coronavirus disease severity. Headache was the most common complaint, reported by just less than half of patients. There was a high mortality rate (30.3%). CVT is a very rare, but potentially life‐threatening complication in patients with COVID‐19. It's mainly reported in relatively young individuals with no or little comorbid disease and can occur even in patients who do not display severe respiratory symptoms. Atypical clinical presentations may pose a challenge to the early diagnosis and treatment. High suspicion is necessary as early diagnosis and prompt treatment with anticoagulation in all patients with COVID‐19 and CVT could contain the mortality rate and improve neurological outcomes in these patients.
Modeling Electrochemical Proton Adsorption at Constant Potential with Explicit Charging
Authors: Kristoffersen Henrik H.
Published: August 2022

An explicit charging approach is presented to account for constant potential in atomic level electrochemistry modeling. Explicit charging allows for the calculation of electrochemical reaction barriers, while also reproducing the results from the computation hydrogen electrode (CHE) approach when the reaction modeled with CHE is at constant potential. Explicit charging is used to obtain activation and adsorption free energies for proton adsorption (the Volmer reaction) from a static water bilayer to the Cu(111) surface. The proton adsorption becomes spontaneous at around 0 V vs RHE and the adsorption free energy changes by around 1 eV per V (similar to the CHE result). The activation free energy changes by around 0.5 eV per V, but is still prohibitively large at 0 V vs RHE. This is consistent with experiments, where hydrogen evolution is only observed below −0.4 V vs RHE.
Synthesis of Enantioenriched Sulfoxides by an Oxidation‐Reduction Enzymatic Cascade
Authors: Wang Peipei , Han Xiaofeng , Liu Xinqi , Lin Richen , Chen Yongzheng , Sun Zhoutong , Zhang Wuyuan
Published: August 2022

Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation–reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium‐dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 %  ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows CiVCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for (S)‐sulfoxide synthesis; the latter case is significantly unexplored for heme‐dependent peroxidases and peroxygenases.
Vinylic Trifluoromethylselenolation via Pd‐Catalyzed C−H Activation
Authors: de Zordo‐Banliat Arnaud , Grollier Kevin , Vigier Jordan , Jeanneau Erwann , Dagousset Guillaume , Pegot Bruce , Magnier Emmanuel , Billard Thierry
Published: August 2022

Trifluorometylselenolation via C−H activation is barely described in literature. In particular, no such vinylic functionalization has been yet described. Herein, a palladium‐catalyzed trifluoromethylselenolation of vinylic C−H bonds is described. The 5‐methoxy‐8‐aminoquinoline has been used as auxiliary directing group to perform this reaction. The reaction gives excellent yields with α‐substituted compounds whatever the substituents and a microwave activation can be used to accelerate the reaction. With β‐substituted substrates lower yields, but still satisfactory, are obtained. This methodology was also successfully extended to other fluoroalkylselenyl groups.
Pru du 1, the Bet v 1‐homologue from almond, is a major allergen in patients with birch pollen associated almond allergy
Authors: Kabasser Stefan , Crvenjak Nadja , Schmalz Stefanie , Kalic Tanja , Hafner Christine , Dubiela Pawel , Kucharczyk Aleksandra , Bazan‐Socha Stanislawa , Lukaszyk Mateusz , Breiteneder Heimo , Radauer Christian , Bublin Merima
Published: August 2022

Background

Almond allergy is common and can manifest in two different forms. Primary almond allergy has been reported to be associated with sensitization to almond legumin Pru du 6. In birchendemic regions, there is a link between birch‐pollinosis which is likely based on a cross‐reactive Bet v 1 homologue, a yet unidentified allergen in almond. Therefore, we sought to identify and characterize a Bet v 1‐homologue in almond.

Methods

The expression of a Bet v 1 homologue in almond kernels was confirmed by mass spectrometry. The recombinant protein was produced in Escherichia coli and its cross‐reactivity and allergenic potency was analyzed by IgE quantitative and competitive ELISA, immunoblotting and basophil histamine release using sera from 17 almond allergic patients.

Results

The identified Bet v 1 homologue received the designation Pru du 1.0101. Pru du 1.0101 bound IgE from 82 % of almond allergic patients. Bet v 1 was able to inhibit IgE‐binding to rPru du 1 by 100%, while rPru du 1 inhibited IgE binding to rBet v 1 by 48%. Pru du 1.0101 activated basophils, though 100‐ to 1000‐fold higher concentrations were required for maximum activation in comparison to rBet v 1.

Conclusion

Considering the strong inhibition capacity and higher allergenic potency of Bet v 1, the results provide compelling evidence for primary sensitization to Bet v 1 in case of birch pollen associated almond allergy. Combining Pru du 6 and Pru du 1 in diagnostic approaches may help to discriminate between primary and birch‐pollen associated almond allergy.
A brain atlas of the carrion crow (Corvus corone)
Authors: Kersten Ylva , Friedrich‐Müller Bettina , Nieder Andreas
Published: August 2022

Corvidae, passerine songbirds such as jays, crows, and ravens known as corvids, have become model systems for the study of avian cognition. The superior cognitive capabilities of corvids mainly emerge from a disproportionally large telencephalon found in these species. However, a systematic mapping of the neuroanatomy of the corvid brain, and the telencephalon in particular, is lacking so far. Here, we present a brain atlas of the carrion crow, Corvus corone, with special emphasis on the telencephalic pallium. We applied four staining techniques to brain slices (Nissl, myelin, combination of Nissl and myelin, and tyrosine hydroxylase targeting catecholaminergic neurons). This allowed us to identify brain nuclei throughout the brain and delineate the known pallial subdivisions termed hyperpallium, entopallium, mesopallium, nidopallium, arcopallium, and hippocampal complex. The extent of these subdivisions and brain nuclei are described according to stereotaxic coordinates. In addition, 3D depictions of pallial regions were reconstructed from these slices. While the overall organization of the carrion crow's brain matches other songbird brains, the relative proportions and expansions of associative pallial areas differ considerably in agreement with enhanced cognitive skills found in corvids. The presented global organization of the crow brain in stereotaxic coordinates will help to guide future neurobiological studies in corvids.
A Porphyrin‐functionalized Graphene Oxide Nanocomposite for Simultaneous Detection of Dopamine and Uric Acid
Authors: Wei Chuangyu , Tu Jingfang , Liu Hanqi , Mei Zhuang , Gao Xinyu , Yu Jinshi , Cai Xue , Li Xiyou , Chen Yanli
Published: August 2022

Carbon nanomaterials combined with porphyrins having the similar electrocatalytic active center to heme protein are quite promising for high‐performance nonenzymatic electrochemical sensor. Herein, the catalytic tetra(4‐aminophenyl) porphyrin (TAPP) molecules are covalent immobilized on the conductive graphene oxide (GO) surface (TAPP@GO) by a simple one‐pot method. TAPP@GO as a novel electrochemical sensor successfully realized the sensitive detection of dopamine (DA) and uric acid (UA) in nM level with high stability and repeatability. The detection limit (LOD) for DA and UA is as low as 38 and 47 nM, and sensitivity up to 40.3 and 54.2 μA mM−1 in a wide detection range from 0.1 to 350 μM, respectively. Impressively, both DA and UA in the coexistence system can be simultaneously determined with the LOD of 51 and 64 nM for DA and UA, which is further confirmed by accurate determination of both in urine samples. This work represents not only the first example of electrochemical sensor based on organic porphyrin molecules covalent linked on GO surface, but more importantly provides an effective method for developing high‐performance sensing materials.
An Open‐Label Study to Evaluate the Effect of Eluxadoline on the Single‐Dose Pharmacokinetics of Midazolam in Healthy Participants
Authors: Boinpally Ramesh , McGeeney Danielle , Kaczynski Edward , Weissman Darren
Published: August 2022

Eluxadoline is a mixed μ‐opioid, κ‐opioid receptor agonist, and δ‐opioid receptor antagonist, approved in the United States for adults with diarrhea‐predominant irritable bowel syndrome. This phase 1, single‐center, open‐label, single‐sequence study was conducted on 30 healthy participants to establish whether steady‐state eluxadoline increases systemic exposure of the cytochrome P450 (CYP) 3A4 substrate midazolam. Participants received oral midazolam 4 mg on day 1 with a 7‐day washout period. On days 8‐16, oral eluxadoline 100 mg was administered twice daily. On day 15, midazolam 4 mg was coadministered with the eluxadoline 100‐mg morning dose. Primary outcome measures were pharmacokinetic parameters of midazolam and 1‐hydroxy‐midazolam. The midazolam and 1‐hydroxy‐midazolam geometric mean ratios and 90%CIs for maximum plasma drug concentration were 99.0% (91.6‐107.0) and 113.8% (104.9‐123.5), respectively, and area under the plasma concentration–time curves were 90.5% (83.9‐97.6) and 105.1% (99.8‐110.7), respectively, demonstrating the 2 treatments were bioequivalent, and there was no clinically significant drug interaction. All treatment‐emergent adverse events were treatment related, mild in intensity, with no serious adverse events. These results suggest that eluxadoline has no clinically significant effect on CYP3A4 activity and is, therefore, unlikely to affect the pharmacokinetics of other CYP3A4 substrates.
Helical Molecule as an Efficient Rectifier: Effects of Molecular Conformation and Transverse Electric Field
Authors: Sarkar Suparna , Maiti Santanu K.
Published: August 2022

The phenomenon of charge current rectification is critically investigated using a single stranded helical molecule in presence of transverse electric field. Two different helical molecules, DNA and protein, are taken into account to explore the specific roles of molecular conformation on rectification, which have not been addressed so far to the best of our concern. Sandwiching the molecular system within source and drain electrodes, we compute charge currents for two bias polarities and the degree of current rectification based on non‐equilibrium Green's function formalism within a tight‐binding framework. At non‐zero electric field, site energies of the molecule are modulated in a cosine form, similar to the well known Aubry‐André‐Harper relation, resulting an atypical and fragmented energy band spectrum. The appearance of non‐uniform site energies plays the central role for generating different currents in two bias polarities, and thus, the current rectification. We find that a high degree of current rectification can be established using the helical system and it becomes more effective for the protein molecule than the DNA one. At the end, the rectification operation considering a more general helical structure is discussed to make the present communication a self‐contained one. Our proposition may provide a new route of getting controlled current rectification using similar kind of biological molecules and other tailor made helical geometries.
Fatigue behavior of removable partial denture cast and laser‐sintered cobalt‐chromium (CoCr) and polyetheretherketone (PEEK) clasp materials
Authors: Zheng Jenny , Aarts John M. , Ma Sunyoung , Waddell John N. , Choi Joanne J. E.
Published: August 2022

Objective

To investigate the fatigue behavior of cast and laser‐sintered cobalt‐chromium (CoCr) and polyetheretherketone (PEEK) material for a removable partial denture (RPD) clasps.

Methods

Dumbbell‐shaped specimens were digitally designed with the center part of the dumbbell being a half‐round shape at the cross‐sectional dimension of 1.25 mm to simulate a typical clasp design and dimensions. A fatigue machine with an offset axis rotation system simulated a typical undercut depth of 0.25, 0.50, and 0.75 mm. Each group was subjected to 30,000 fatigue cycles (simulating 21 years) or till specimen failure. Before testing, the stress value at each undercut depth for each specimen was established in a universal testing machine and SN curves were plotted for each group. Data were statistically analyzed using Kruskal–Wallis and post hoc tests. The fractured surfaces were analyzed using SEM.

Results

The average fatigue cycles with 0.25, 0.50, and 0.75 mm undercuts were 27,155 ± 6277, 9298 ± 4033, 5642 ± 8785 for cast CoCr and 26,765 ± 6150, 11,318 ± 7931, 2861 ± 4803, for laser‐sintered CoCr, respectively. Apart from three specimens, the PEEK groups did not fail during the simulation period. Clasps with 0.25 mm deflection showed significantly higher fatigue resistance than other groups (p < .001). There was no significant difference in fatigue behavior between the cast and laser‐sintered CoCr. Microporosities at the fractured site along with irregular crack propagation were observed for cast and laser‐sintered CoCr specimens. Fatigue‐induced broken polymer crosslinking chains were observed in PEEK specimens.

Conclusion

PEEK material exhibited the highest fatigue resistance and significantly lower deflection resistance. Cast and laser‐sintered CoCr showed similar fatigue resistance and behavior.
Tuning d‐Band Structure of CuII in Coordinated Polymer via d–π Conjugation for Improving CO2 Electroreduction Selectivity toward C2 Products
Authors: Zhang Fengtao , Wang Peng , Zhao Runyao , Wang Yiding , Wang Jianji , Han Buxing , Liu Zhimin
Published: August 2022

Copper‐coordinated catalysts are reported to be effective for electrocatalytic CO2 reduction reaction (CO2RR) to C2 products but suffer from low selectivity. Herein a strategy was developed to tune the d‐band structure of CuII via coordinating with aromatic ligands to form Cu‐based conjugated polymers for CO2RR to C2 chemicals. The catalysts derived from copper chloride coordinating with tetraminobenzoquinone (TABQ) and with 1,2,4,5‐benzenetetramine possessed high‐density and compact Cu single‐atom sites and displayed high activity for CO2RR to C2 products. Especially, Cu‐TABQ exhibited a maximum C2 faradaic efficiency of 63.2 % with a current density of 423 mA cm−2 at −1.17 V (vs. reversible hydrogen electrode). Density functional theory calculations indicated that the TABQ linker possessing C=O groups significantly widened the d‐band of coordinated CuII, which facilitated binding of *CO intermediate on the catalyst and thus enhanced C−C coupling. This work provides mechanistic insight into the CuII‐coordinated polymers for CO2RR with high selectivity toward C2 products.
Seismic microzoning of the Delhi metropolitan area, India—II: Hazard computation and zoning maps
Authors: Gupta Ishwer Datt , Lee Vincent W. , Trifunac Mihailo D.
Published: August 2022

We present seismic microzonation maps of New Delhi, India, using the probabilistic seismic hazard analysis (PSHA) method with input seismic activity parameters estimated in Part‐I of this two‐part paper. Our calculations required three different attenuation equations for amplitude scaling of strong ground motion from three principal contributing sources: the National Capital Region (NCR), Northwestern Himalaya (NWH), and the Hindu Kush subduction (HKS). We show that uniform hazard spectral (UHS) amplitudes are dominated only by the local seismicity in the NCR at high frequencies beyond about 2 Hz. For intermediate and long periods, UHS amplitudes are dominated by contributions from the NWH and HKS earthquakes. Our results show that specifying strong motion amplitudes for use in engineering design by means of peak ground acceleration can lead to serious errors for buildings higher than four to five stories and hence should not be used. Our results also show that the shape of design spectra must depend on the nature of contributing earthquake sources, their relative activity, potential to create large magnitudes, and geographical placement relative to the site of interest, and thus a standard design‐spectrum shape cannot satisfy all these requirements. We use local geological site condition parameters directly in all calculations and present hazard maps for three different soil site conditions (“rock,” stiff soil sites, and deep soil sites). Thus, the user can extract the UHS amplitudes of pseudo relative velocity spectra at any site in the National Capital Territory by experimentally determining the local soil site conditions and then applying the corresponding maps shown in this paper.
Near‐fault ground motion effects on pounding and unseating using an example of a three‐span, simply supported bridge
Authors: Khakzand Leila , Jalali Reza S. , Veisi Milad
Published: August 2022

A simple model of a three‐span, simply supported bridge consisting of three rigid decks supported by two axially rigid piers and rigid abutments at two ends is analyzed by solving the dynamic differential equations. The response spectrum method is not considered, and it is assumed that there is no soil–structure interaction. The bridge is acted upon by the acceleration of gravity, g, and excited by differential horizontal‐, vertical‐, and point‐ and cord‐rocking components of near‐fault ground motion. The model's in‐plane linear response shows that the vertical and rocking ground‐motion components have no noticeable effect on the maximum pounding force between bridge segments when computed for horizontal ground motion only. For the model with system periods longer than 1 s subjected to the strong motion pulse corresponding to magnitude M = 7, the vertical ground‐motion component contributes to the destabilizing effect of the gravity. For bridge periods longer than 0.5 s, the simultaneous action of horizontal and vertical ground‐motion components can noticeably increase the minimum gap size required to prevent pounding and the minimum seating length to avoid the unseating of bridge segments when computed for horizontal ground motion only. For system periods shorter than 1 s, the time delay of input ground motion has a significant effect on the minimum gap size to prevent pounding as well as on the minimum seating length to avoid unseating of the deck. The response of the bridge subjected to differential horizontal, vertical, and point‐rocking ground‐motion components is almost the same as the response under differential horizontal and vertical components of the ground motion. The main contribution to changes in the response, which is computed for horizontal ground motion only, is caused by the vertical and cord rocking of the ground motion. The minimum seating length to avoid the unseating of bridge segments suggested in seismic Iranian Code, No: 463 (Road and railway bridges seismic‐resistant design code, 2008), is conservative for pulses with magnitudes M = 5 and 6, but not conservative for bridge periods longer than about 0.6 s and a near‐field pulse with M = 7 magnitude.
Stereoconvergent Synthesis of Cyclopentenyl Nucleosides by Palladium‐Assisted Allylic Reaction
Authors: Esposito Anna , Talarico Giovanni , De Fenza Maria , D'Alonzo Daniele , Guaragna Annalisa
Published: August 2022

The Tsuji‐Trost reaction of cyclopentenyl carbonates was explored by experimental studies and computational calculations, in search for the synthetic conditions enabling the stereoconvergent synthesis of cyclopentenyl nucleosides. Under common conditions, cyclopentenyl reagents provide Tsuji‐Trost products only in a weakly stereoconvergent manner. However, changes in the amount of catalyst (up to 1 eq) affect either the regio‐ and stereoselectivity of the reaction, selectively leading to cis configured cyclopentenyl N9‐linked purine nucleosides, regardless the relative configuration (cis or trans) of the starting substrates. DFT studies clarified that this could be due to the low activation energy related to the crucial, Pd‐dependent π‐inversion step.
Describing engagement practices for the Enhance Diversity Study using principles of Tailored Panel Management
Authors: Ramirez Karina D. , Joseph Cynthia J. , Oh Hansook
Published: August 2022

The purpose of this chapter is to examine engagement strategies used in a large, multisite evaluation study through the lens of Estrada, Woodcock, and Schultz's (2014) tailored panel management. The evaluation, called the Enhance Diversity Study (EDS), is part of an effort funded by the National Institutes of Health (NIH) to increase diversity in NIH‐funded research. The chapter discusses engagement with a large national cohort of student participants and outlines survey administration complexities, tailored engagement approaches, and annual survey response trends. It shows how the EDS expanded Estrada and colleagues’ concepts of credibility by integrating branding strategies that permeated all aspects of the study. The resulting practices, as modified over time, extend knowledge of how to increase survey response rates across a multisite, multiprogram, longitudinal evaluation. As data collection continues, subsequent analysis may provide more clarity on the impact of these strategies on retention. Future researchers should explore the impacts of incorporating fully developed branding strategies to enhance study commitment and cohort retention. While past research has guided surveys through phone, mail, and multimodal distribution, more research is needed to understand how to engage participants and retain them in an increasingly competitive and digital world.
The funders’ perspective: Lessons learned from the National Institutes of Health Diversity Program Consortium evaluation
Authors: Gibbs Kenneth D. , Reynolds Christa , Epou Sabrina , Gammie Alison
Published: August 2022

Advancing diversity in the biomedical research workforce is critical to the ability of the National Institutes of Health (NIH) to achieve its mission. The NIH Diversity Program Consortium is a unique, 10‐year program that builds upon longstanding training and research capacity‐building activities to promote workforce diversity. It was designed to rigorously evaluate approaches to enhancing diversity in the biomedical research workforce at the student, faculty, and institutional level. In this chapter we describe (a) the program's origins, (b) the consortium‐wide evaluation, including plans, measures, challenges, and solutions, and (c) how lessons learned from this program are being leveraged to strengthen NIH research‐training and capacity‐building activities and evaluation efforts.
Understanding the context and appreciating the complexity of evaluating the Diversity Program Consortium
Authors: Guerrero Lourdes R. , Seeman Teresa , McCreath Heather , Maccalla Nicole M.G. , Norris Keith C.
Published: August 2022

The National Institutes of Health (NIH) made a sizeable investment in developing a scientific approach to understanding how to best increase diversity in the NIH‐funded workforce by fostering inclusive excellence at a national scale through the Diversity Program Consortium (DPC). This chapter provides an overview of the context in which the consortium‐wide evaluation study has taken place to provide readers with an understanding of its level of complexity. This evaluation effort is the first large‐scale, national, systemic, longitudinal evaluation of harmonized interventions focused on undergraduate biomedical research training programs in the history of the NIH and the National Institute of General Medical Sciences.
Gauging treatment impact: The development of exposure variables in a large‐scale evaluation study
Authors: Maccalla Nicole M. G. , Purnell Dawn , McCreath Heather E. , Dennis Robert A. , Seeman Teresa
Published: August 2022

While guidance on how to design rigorous evaluation studies abounds, prescriptive guidance on how to include critical process and context measures through the construction of exposure variables is lacking. Capturing nuanced intervention dosage information within a large‐scale evaluation is particularly complex. The Building Infrastructure Leading to Diversity (BUILD) initiative is part of the Diversity Program Consortium, which is funded by the National Institutes of Health. It is designed to increase participation in biomedical research careers among individuals from underrepresented groups. This chapter articulates methods employed in defining BUILD student and faculty interventions, tracking nuanced participation in multiple programs and activities, and computing the intensity of exposure. Defining standardized exposure variables (beyond simple treatment group membership) is crucial for equity‐focused impact evaluation. Both the process and resulting nuanced dosage variables can inform the design and implementation of large‐scale, diversity training program, outcome‐focused, evaluation studies.
Endocannabinoid signaling in synaptic function
Authors: Noriega‐Prieto Jose Antonio , Kofuji Paulo , Araque Alfonso
Published: August 2022

In the last decades, astrocytes have emerged as important regulatory cells actively involved in brain function by exchanging signaling with neurons. The endocannabinoid (eCB) signaling is widely present in many brain areas, being crucially involved in multiple brain functions and animal behaviors. The present review presents and discusses current evidence demonstrating that astrocytes sense eCBs released during neuronal activity and subsequently release gliotransmitters that regulate synaptic transmission and plasticity. The eCB signaling to astrocytes and the synaptic regulation mediated by astrocytes activated by eCBs are complex phenomena that exhibit exquisite spatial and temporal properties, a wide variety of downstream signaling mechanisms, and a large diversity of functional synaptic outcomes. Studies investigating this topic have revealed novel regulatory processes of synaptic function, like the lateral regulation of synaptic transmission and the active involvement of astrocytes in the spike‐timing dependent plasticity, originally thought to be exclusively mediated by the coincident activity of pre‐ and postsynaptic neurons, following Hebbian rules for associative learning. Finally, the critical influence of astrocyte‐mediated eCB signaling on animal behavior is also discussed.
Will the latest wave of the COVID‐19 pandemic be an ecological disaster? There is an urgent need to replace plastic by ecologically virtuous materials
Authors: Mansuy Jean‐Michel , Migueres Marion , Trémeaux Pauline , Izopet Jacques
Published: August 2022

Background and Aims

Direct virological diagnosis of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS‐CoV‐2) infectionis based on either viral antigen or viral genome detection. These methods, in addition to the dedicated reagents and transport packaging, require the use of quantities of plastic that may individually appear negligible but which, in the context of a pandemic, are very high. The aim was to estimate the amount of plastic involved in a diagnostic assay whether molecular or antigenic.

Methods

We weighed the plastics used to obtain a diagnostic assay result for SARS‐CoV‐2 infection in our hospital.

Results

Each ready‐to‐use antigen assay requires about 20 g of plastic whereas the PCR assay implies the use of 30 g. This unit mass, when compared to our laboratory's SARS‐CoV‐2 genomic screening activity,represents more than 10 tons of plastic for 2021. At our region level (#6.10 inhabitants), more than 350 tons of plastic were used to carry out more than 7 million declared PCR assays and as many antigenic assays.

Conclusions

The virologic diagnostic activityl inked to the SARS‐CoV‐2 pandemic has highlighted once more our dependance for plastic use. We must already think about a more environmentally virtuous diagnostic activity by integrating a reasonned use of diagnostic tools and a higher use of ecological friendly material. Parallel the notion of waste management must also be addressed in order to limit their environmental impact.
Prevalence of migraine and tension‐type headache among undergraduate medical students of Kathmandu Valley: A cross‐sectional study
Authors: Shrestha Oshan , Karki Sagun , Thapa Niranjan , Lal Shrestha Kabindra , Shah Aayushama , Dhakal Pramita , Pant Prashant , Dhungel Sunil , Shrestha Dhan Bahadur
Published: August 2022

Background

Headache is the most prevalent neurological symptom which can be of a serious condition, as in brain tumor, but mostly it is a benign condition that includes primary headache such as migraine or tension‐type headache (TTH). Migraine reoccurs frequently and is more severe but owing to the high prevalence of TTH, however, impaired quality of life due to TTH is greater than that of migraine at the population level. Medical students are constantly subjected to stress and in such a condition, it was necessary to find out the burden of headache among medical students. This cross‐sectional study done among medical students aims to generate some data and literature which will change the outlook of stakeholders towards headache disorders among medical students.

Methods

This cross‐sectional study is based upon Headache Screening Questionnaire—English Version questionnaire based upon the ICHD‐3 beta criteria. Medical students of Kathmandu valley were sampled by using convenient sampling and data were collected. Data were refined in Microsoft Excel and imported to SPSS 20 for analysis.

Results

A total of 352 individuals were part of this study, out of which 229 (65.1%) were males and 123 (34.9%) were females with a mean age of 21.72 ±  1.601 years (mean ± SD). Prevalence of migraine and TTH was found to be 15.3% (95% confidence interval [CI]: 11.7%–19.3%) and 40.3% (95% CI: 34.9–45.2), respectively. Through multivariate binomial regression, it was observed that the odds of being diagnosed with migraine increased with age (adjusted odds ratio [AOR] = 1.266 [1.013–1.583], p = 0.038), females had twice the odds of experiencing migraine headaches compared to males (AOR = 2.119 [1.074–4.180], p = 0.03), and medical students who stayed at the hostel were at lesser odds of experiencing migraine headache (AOR = 2.772 [1.501–5.118], p = 0.01).

Conclusion

Prevalence of migraine and TTH among undergraduate medical students was found to be 15.3% and 40.3%, respectively.