bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of Out-of-Pocket Costs for Guideline-Directed Medical Therapy for Heart Failure Under Medicare Part D and the Inflation Reduction Act
Authors: Johnson Micah , Nayak Rahul K. , Gilstrap Lauren , Dusetzina Stacie B.
Published: January 2023

This cross-sectional study estimates out-of-pocket costs of heart failure with reduced ejection fraction medication regimens in Medicare Part D under current law and the Inflation Reduction Act.
Drug Reaction With Eosinophilia and Systemic Symptoms
Authors: Krantz Matthew S. , Phillips Elizabeth J.
Published: January 2023

This Patient Page describes the symptoms, diagnosis, and treatment of drug reaction with eosinophilia and systemic symptoms.
Stability of dosiomic features against variations in dose calculation: An analysis based on a cohort of prostate external beam radiotherapy patients
Authors: Sun Lingyue , Smith Wendy , Kirkby Charles
Published: January 2023

Introduction

Interest in using higher order features of the planned 3D dose distributions (i.e., dosiomics) to predict radiotherapy outcomes is growing. This is driving many retrospective studies where historical data are mined to train machine learning models; however, recent decades have seen considerable advances in dose calculation that could have a direct impact on the dosiomic features such studies seek to extract. Is it necessary to recalculate planned dose distributions using a common algorithm if retrospective datasets from different institutions are included? Does a change in dose calculation grid size part way through a retrospective cohort, introduce bias in the extracted dosiomic features? The purpose of this study is to assess the stability of dosiomic features against variations in three factors: the dose calculation algorithm type, version, and dose grid size.

Methods

Dose distributions for 27 prostate patients who received EBRT were recalculated in the Eclipse Treatment Planning System (Varian Medical Systems, Palo Alto, California, USA) using two algorithms (AAA and Acuros XB), two versions (version 13.6 and 15.6), and three dose grids (2, 2.5 s, and 3 mm) – 12 dose distributions for each patient. Ninety‐three dosiomic features were extracted from each dose distribution and each of the following regions‐of‐interest: high dose PTV (PTV_High), 1 cm rind around PTV_High (PTV_Ring), low dose PTV (PTV_Low), rectum, and bladder using PyRadiomics. The coefficient of variation (CV) was calculated for each dosiomic feature. Hierarchical clustering was used to group features with high and low variability. Three‐way repeated measures ANOVA was performed to investigate the effect of the three different factors on dosiomic features that were classified with high variation. Additionally, CVs were calculated for cumulative dose volume histograms (DVHs) to test their ability to detect the variations in dose distributions.

Results

For PTV_Ring, PTV_Low, and rectum, all the dosiomic features had low CV (average CV ≤ 0.26) across the varying dose calculation conditions. For PTV_High, six dosiomic features showed CV > 0.26, and dose calculation algorithm type and grid size were the major sources of within‐patient variation. For bladder, one dosiomic feature had average CV > 0.26, but none of the three dose calculation‐related factors led to a statistically significant variation. The CVs for all the DVHs were very small (CV < 0.05).

Conclusion

For all the regions‐of‐interest examined in this study, the majority of the dosiomic features were stable against variations in dose calculation; however, some of the dosiomic features for PTV_High and bladder had significant variations due to differences in dose calculation details. DVHs were detecting less variation than dosiomic features.
Advances in Triboelectric Nanogenerators for Self‐powered Neuromodulation
Authors: Elsanadidy Esraa , Mosa Islam M. , Luo Dan , Xiao Xiao , Chen Jun , Wang Zhong Lin , Rusling James F.
Published: January 2023

Advances in implantable bioelectronics for the nervous system are reinventing the stimulation, inhibition, and sensing of neuronal activity. These efforts promise not just breakthrough treatments of several neurological and psychiatric conditions but also signal the beginning of a new era of computer‐controlled human therapeutics. Batteries remain the major power source for all implanted electrical neuromodulation devices, which impairs miniaturization and necessitates replacement surgery when the battery is drained. Triboelectric nanogenerators (TENGs) have recently emerged as an innovative power solution for self‐powered, closed loop electrical neurostimulation devices. TENGs can leverage the biomechanical activities of different body organs to sustainably generate electricity for electrical neurostimulation. This review features advances in TENGs as they pave the way for self‐sustainable closed loop neurostimulation. A comprehensive review of TENG research for the neurostimulation of brain, autonomic, and somatic nervous systems is provided. The direction of growth of this field, publication trends, and modes of TENG in implantable bioelectronics are also discussed. Finally, an insightful outlook into challenges facing self‐sustainable neuromodulators to reach clinical practice is provided, and solutions for neurological maladies are proposed.
A Machine‐Learning‐Based Approach for Solving Atomic Structures of Nanomaterials Combining Pair Distribution Functions with Density Functional Theory
Authors: Kløve Magnus , Sommer Sanna , Iversen Bo B. , Hammer Bjørk , Dononelli Wilke
Published: January 2023

Determination of crystal structures of nanocrystalline or amorphous compounds is a great challenge in solid‐state chemistry and physics. Pair distribution function (PDF) analysis of X‐ray or neutron total scattering data has proven to be a key element in tackling this challenge. However, in most cases, a reliable structural motif is needed as a starting configuration for structure refinements. Here, an algorithm that is able to determine the crystal structure of an unknown compound by means of an on‐the‐fly trained machine learning model, which combines density functional theory calculations with comparison of calculated and measured PDFs for global optimization in an artificial landscape, is presented. Due to the nature of this landscape, even metastable configurations and stacking disorders can be identified.
Dual Topology of Dirac Electron Transport and Photogalvanic Effect in Low‐Dimensional Topological Insulator Superlattices
Authors: Xue Hao‐pu , Sun Rui , Yang Xu , Comstock Andrew , Liu Yangrui , Ge Binghui , Liu Jia‐nan , Wei Yan‐sheng , Yang Qing‐lin , Gai Xue‐song , Gong Zi‐zhao , Xie Zong‐kai , Li Na , Sun Dali , Zhang Xiang‐qun , He Wei , Cheng Zhao‐hua
Published: January 2023

Dual topological insulators, simultaneously protected by time‐reversal symmetry and crystalline symmetry, open great opportunities to explore different symmetry‐protected metallic surface states. However, the conventional dual topological states located on different facets hinder integration into planar opto‐electronic/spintronic devices. Here, dual topological superlattices (TSLs) Bi2Se3‐(Bi2/Bi2Se3)N with limited stacking layer number N are constructed. Angle‐resolved photoelectron emission spectra of the TSLs identify the coexistence and adjustment of dual topological surface states on Bi2Se3 facet. The existence and tunability of spin‐polarized dual‐topological bands with N on Bi2Se3 facet result in an unconventionally weak antilocalization effect (WAL) with variable WAL coefficient α (maximum close to 3/2) from quantum transport experiments. Most importantly, it is identified that the spin‐polarized surface electrons from dual topological bands exhibit circularly and linearly polarized photogalvanic effect (CPGE and LPGE). It is anticipated that the stacked dual‐topology and stacking layer number controlled bands evolution provide a platform for realizing intrinsic CPGE and LPGE. The results show that the surface electronic structure of the dual TSLs is highly tunable and well‐regulated for quantum transport and photoexcitation, which shed light on engineering for opto‐electronic/spintronic applications.
Detailed analysis of the particle residence time distribution in a pressurized drop‐tube reactor
Authors: An Fengbo , Dai Zhenghua , Guhl Stefan , Gräbner Martin , Richter Andreas
Published: January 2023

Solid fuel conversion in a pressurized drop‐tube reactor is studied in detail using a three‐dimensional computational fluid dynamics (CFD) model. The main focus is on analyzing individual particle trajectories and residence times, as these data are crucial for the precise experimental estimation of heterogeneous reaction kinetics. The numerical results were substantiated by radioactive tracer measurements carried out in different operating conditions. The numerical results reveal a complex gas flow that is affected by buoyancy due to a non‐homogeneous temperature distribution, which has a strong affect on the trajectories of particular particle size fractions. In this case, empirical residence time correlations for particles, as commonly used for the evaluation of heterogeneous kinetic measurements, lose their validity since the assumption of a plug flow is no longer valid. It can be shown that if CFD‐assisted data evaluation is used, a significant improvement in the measured heterogeneous reaction kinetics is feasible.
Job and exposure intensity among hospital cleaning staff adversely affects respiratory health
Authors: Ndlela Nana Happiness , Naidoo Rajen N.
Published: January 2023

Background

Occupational exposure to various types of cleaning agents may increase the risk of adverse respiratory health among cleaners. This study investigated the relationship between exposure to cleaning and disinfecting agents, using a job‐task and exposure intensity metric, and respiratory outcomes among cleaners.

Methods

A sample of 174 cleaners was selected from three public hospitals in Durban. A questionnaire was used to collect demographic and occupational information, and spirometry, including post‐bronchodilator measures, was conducted according to the American Thoracic Society guidelines and skin prick testing were performed. Exposure metrics for job tasks and chemical exposures were created using frequency and employment‐lifetime duration of exposure. Multivariate analysis regression models used job task and exposure intensity metrics.

Results

Doctor‐diagnosed asthma prevalence was 9.8%. Breathlessness with wheeze (22.4%) was the prevalent respiratory symptom. Positive responses to skin prick testing were seen in 74 (43.2%). There was a statistically significant increased risk for shortness of breath with exposure to quaternary ammonium compounds (odds ratio [OR]: 3.44; 95% confidence interval [CI]: 1.13–10.5) and breathlessness with exposure to multipurpose cleaner (OR: 0.34; CI: 0.12–0.92). The losses in percent‐predicted forced expiratory volume in 1 s (FEV1) ranged from 0.3%–6.7%. Results among the bronchodilator‐positive (8.6%) showed lung function losses twofold greater when compared to the total study population with percentage predicted FEV1 (−22.6 %; p < 0.000).

Conclusion

Exposure to certain cleaning and disinfectant agents adversely affects respiratory health, particularly lung function. This effect, while seen generally among cleaning workers, is more pronounced among those with pre‐existing reversible obstructive lung disease.
Deletion of first noncoding exon in ANKRD11 leads to KBG syndrome
Authors: Borja Nicholas , Zafeer Mohammad Faraz , Rodriguez Jeimy Alfonso , Morel Swols Dayna , Thorson Willa , Bademci Guney , Tekin Mustafa
Published: January 2023

Phenotypic features of KBG syndrome include craniofacial anomalies, short stature, cognitive disability and behavioral findings. The syndrome is caused by heterozygous pathogenic single nucleotide variants and indels in ANKRD11, or a heterozygous deletion of 16q24.3 that includes ANKRD11. We performed genome sequencing on a patient with clinical manifestations of KBG syndrome including distinct craniofacial features as well as a history of mild intellectual disability and attention‐deficit hyperactivity disorder. This led to the identification of a 43 kb intragenic deletion of ANKRD11 affecting the first noncoding exon while leaving the coding regions intact. Review of the literature shows that this is the smallest 5′ deletion affecting only the noncoding exons of ANKRD11. Real‐time polymerase chain reaction demonstrated that the copy number variant was not present in either of the proband's parents, suggesting it occurred de novo. RNA expression analysis demonstrated significantly decreased transcript abundance compared to controls. This provides new evidence for haploinsufficiency as a mechanism of disease in KBG syndrome.
A novel biallelic CRIPT variant in a patient with short stature, microcephaly, and distinctive facial features
Authors: Akalın Akçahan , Şimşek‐Kiper Pelin Özlem , Taşkıran Ekim Z. , Karaosmanoğlu Beren , Utine Gülen Eda , Boduroğlu Koray
Published: January 2023

Primordial dwarfism (PD) is one of a highly heterogeneous group of disorders characterized by severe prenatal/postnatal growth restriction. Defects in various pathways such as DNA repair mechanism, impaired centrioles, abnormal IGF expression, and spliceosomal machinery may cause PD including Seckel syndrome, Silver–Russell syndrome. Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, II, and Meier–Gorlin syndrome. In recent years with the wide application of exome sequencing (ES) in the field of PD, new genes involved in novel pathways causing new phenotypes have been identified. Pathogenic variants in CRIPT (MIM# 604594) encoding cysteine‐rich PDZ domain‐binding protein have recently been described in patients with PD with a unique phenotype. This phenotype is characterized by prenatal/postnatal growth restriction, facial dysmorphism, ocular abnormalities, and ectodermal findings such as skin lesions with hyper/hypopigmented patchy areas and hair abnormalities. To our knowledge, only three patients with homozygous or compound heterozygous variants in CRIPT have been reported so far. Here, we report on a male patient who presented with profound prenatal/postnatal growth restriction, developmental delay, dysmorphic facial features, and skin lesions along with the findings of bicytopenia and extensive retinal pigmentation defect. A novel truncating homozygous variant c.7_8delTG; p.(Cys3Argfs*4) was detected in CRIPT with the aid of ES. With this report, we further expand the mutational and clinical spectrum of this rare entity.
Adolescents at risk of mental health problems in the COVID‐19 pandemic: A prospective population‐based study of the effects of government mandates and school closures
Authors: Mundy Lisa K. , Canterford Louise , Dashti S. Ghazaleh , Husin Hanafi Mohamad , Beatson Ruth , Edwards Ben , Patton George C.
Published: January 2023

There is increasing evidence that the COVID‐19 pandemic has had substantial mental health impacts for adolescents. Yet, few definitive studies have investigated which adolescents were at higher risk of poor mental health and well‐being during the pandemic. Data were drawn from the Childhood to Adolescence Transition Study, a prospective cohort study of students in Australia (N = 1211). Prevalence of mental health outcomes (depressive symptoms, anxiety symptoms, self‐harm and good subjective well‐being) was estimated in school Years 5–12, where Years 11 (2020) and 12 (2021) coincided with the pandemic. The age‐ and sex‐adjusted relative risk of each mental health outcome for each priority group during the pandemic were estimated. During the pandemic, over 50% of study participants reported depressive symptoms, and one quarter reported anxiety symptoms. There was a decrease in good subjective well‐being compared with pre‐pandemic years, while self‐harm prevalence remained similar. History of mental health problems, school disengagement and frequent peer victimisation increased the risk of experiencing mental health problems during the pandemic. Schools play a central role in maintaining the mental health and good subjective well‐being of students, and this is particularly important during periods of social disruption, such as the COVID‐19 pandemic.
The contribution of blockchain technologies to anti‐corruption practices: A systematic literature review
Authors: Trequattrini Raffaele , Palmaccio Matteo , Turco Mario , Manzari Alberto
Published: January 2023

This paper proposes a systematic literature review emphasising scholars' view on the impact of the adoption of blockchain technologies to fight corruption. Providing a deep understanding of the state of the art, the paper drafts implications and valuable insights to address future research. The connection of anticorruption policies and blockchain technologies has been investigated using Scopus database and ABS journal ranking. The importance assumed by anticorruption policies and the innovativeness of the blockchain technology, thanks to its characteristics of immutability, automatic timestamping and distributed architecture, needs to be investigated in an integrated perspective. This study provides for the first time a systematic connection among anticorruption practices and blockchain towards the lens of the business, management and accounting field, providing valuable implications, insights and emerging issues.
Effect of Flowering Stages on the Content of Active Ingredients and Antioxidant Capability of Bletilla striata Flowers
Authors: Wang Zhen , Liu Xinting , Wang Jie , Fan Zepeng , Shen Jiayu , Chen Yuanxing , Shao Qingsong , Zheng Ying
Published: January 2023

Bletilla striata (Thunb.) Reichb.f. is a perennial herb with abundant active ingredients. Previous research mainly focused on its tubers, however, the study on flowers, especially the variation of active ingredient contents at different flowering stages, was rarely seen. This study analyzed the total phenols, flavonoids, polysaccharides, anthocyanins, and cyanidin‐3‐O‐glucoside content of B. striata flowers which were in cultivated in Herb Garden of Zhejiang A&F University and collected in May, 2019, in order to investigate the changes in active ingredients and antioxidant capacity among different flowering stages (bud, initial, and full bloom). Changes in radical scavenging capability of DPPH (1,1‐Diphenyl‐2‐picrylhydrazyl radical), ABTS (2,2′‐azinobis(3‐ethylbenzthiazoline‐6‐sulphonate)), and hydroxy were analyzed. Significant differences in active ingredient content of flowers were detected among different flowering stages. The total phenolic content increased continuously during the entire flowering stage. The contents of total flavonoid, total polysaccharide, and cyanidin‐3‐O‐glucoside reached peaks at the initial blooming stage and then fell as the flowering process continued. The antioxidant activity in initial stage was the highest than in any other flowering stages. Therefore, we conclude that the initial blooming stage is the best harvesting stage of B. striata flowers. This study provides a robust basis for the harvest and utilization of B. striata flowers in food, medical, and cosmetic industries.
Feasibility, safety, and efficacy of Atrial Flow Regulator in children under 10 kg
Authors: Bautista‐Rodriguez Carles , Hascoët Sébastien , Fraisse Alain
Published: January 2023

Introduction

The Atrial Flow Regulator (AFR) is a new self‐expandable percutaneous‐delivered fenestrated device providing an interatrial shunt. Its use in pediatric population has been reported in failing Fontan, pulmonary hypertension, or in patients with cardiomyopathy and venoarterial extracorporeal membrane oxygenator (ECMO) support. Its use in small children under 10 kg has not been reported.

Methods

We report the initial single center experience of the AFR implantation in children below 10 kg.

Results

Four children underwent AFR implantation. Patients' age and weight ranged between 9 and 22 months and 5−8.7 kgs. Indications were to unload the left atrium during ECMO support for end‐stage cardiomyopathy and to enlarge a restrictive interatrial shunt in two other patients with complex congenital heart diseases. Devices implanted were AFR‐6 and AFR‐8. Delivery sheaths used via venous femoral access were undersized and ranged from 9 to 11 Fr. Devices were successfully implanted and provided unrestrictive interatrial shunt in all cases. One child developed a nonocclusive thrombus in the inferior vena cava which resolved within 1 month. Clinical improvement and femoral vein patency were observed in all cases.

Conclusion

AFR implantation is feasible in selected children under 10 kg. The AFR can be safely deployed through sheaths that are 1−2 Fr smaller than the recommended manufacturer size. More studies are needed to confirm safety and efficacy of the device in selected pediatric patients.
Intravascular lithotripsy in the treatment of coronary artery calcification in a high‐risk real world population
Authors: Yeoh Julian , Kanyal Ritesh , Pareek Nilesh , Macaya Fernando , Cannata Stefano , Tzalamouras Vasileos , Webb Ian , Dworakowski Rafal , Melikian Narbeh , Shah Ajay M. , MacCarthy Philip , Hill Jonathan , Byrne Jonathan
Published: January 2023

Background

The DISRUPT‐CAD study series demonstrated feasibility and safety of intravascular lithotripsy (IVL) in selected patients, but applicability across a broad range of clinical scenarios remains unclear.

Aims

This study aims to evaluate the procedural and clinical outcomes of IVL in a high‐risk real‐world cohort, compared to a regulatory approval cohort.

Methods

Consecutive patients treated with IVL and percutaneous coronary intervention at our center from May 2016 to April 2020 were included. Comparison was made between those enrolled in the DISRUPT‐CAD series of studies to those with calcified lesions but an exclusion criteria.

Results

Among 177 patients treated with IVL, 142 were excluded from regulatory trials due to acute coronary syndrome presentation (47.2%), left ventricular ejection fraction <40% (22.5%), chronic renal failure (12.0%), or use of mechanical circulatory support (8.5%). This clinical cohort had a higher SYNTAX score (22.6 ± 12.1 vs. 17.4 ± 9.9, p = 0.019), and more treated ACC/AHA C lesions (56.3% vs. 37.1%, p = 0.042). Rates of device success (93.7% vs. 100.0%, p = 0.208), procedural success (96.5% vs. 100.0%, p = 0.585), and minimal lumen area gain (221.2 ± 93.7% vs. 198.6 ± 152.0%, p = 0.807) were similar in both groups. The DISRUPT‐CAD cohort had no in‐hospital mortality, 30‐day major adverse cardiac events (MACE), or 30‐day target vessel revascularization (TVR). The clinical cohort had an in‐hospital mortality of 4.2%, 30‐day MACE of 7.8%, and 30‐day TVR of 1.5%. There was no difference in 12‐month TVR (2.9% vs. 2.2%; p = 0.825). Twelve‐month MACE was higher in the clinical cohort (21.1% vs. 8.6%, p = 0.03).

Conclusion

IVL use remains associated with high clinical efficacy, procedural success, and low complication rates in a real‐world population previously excluded from regulatory approving trials.
Impact of sex on in‐hospital mortality and 90‐day readmissions in patients undergoing transcatheter mitral valve replacement (TMVR): Analysis from the nationwide readmission database
Authors: Ismayl Mahmoud , Machanahalli Balakrishna Akshay , Fahmy Mostafa Mahmoud , Thandra Abhishek , Gill Gauravpal S. , Niu Fang , Agarwal Himanshu , Aboeata Ahmed , Goldsweig Andrew M. , Smer Aiman
Published: January 2023

Objectives

To evaluate sex differences in in‐hospital mortality and 90‐day readmission rates among patients undergoing transcatheter mitral valve replacement (TMVR) in the United States of America.

Background

Women have higher rates of mortality and rehospitalization than men following many cardiac procedures. TMVR has grown as an alternative to mitral valve surgery for patients at high surgical risk. The rates of TMVR mortality and rehospitalization by sex are unknown.

Methods

We analyzed the Nationwide Readmissions Database (NRD) from 2016 to 2019 to identify hospitalizations for TMVR. Sex differences in in‐hospital mortality and 90‐day readmissions were determined using logistic regression models.

Results

Between 2016 and 2019, 4109 hospitalizations for TMVR were identified, comprised of 1758 (42.8%) men and 2351 (57.2%) women. The median age was 74 years for both men and women. There was no significant difference in in‐hospital mortality during index hospitalization (6.51% vs. 6.69%; p = 0.852) and all‐cause 90‐day readmission (28.19% vs. 29.59%; p = 0.563) between men and women. Across the study period, trend analysis did not reveal a significant change in in‐hospital mortality (men p = 0.087, women p = 0.194) or 90‐day readmission rates (men p = 0.569, women p = 0.454).

Conclusions

In patients undergoing TMVR, in‐hospital mortality and 90‐day readmissions are similar between men and women. Between 2016 and 2019, TMVR in‐hospital mortality and 90‐day readmission rates remained unchanged. Further research is necessary to confirm these findings.
The association between childhood trauma and pain symptoms in depressed adults: The moderating role of anxious attachment
Authors: Zhang Kai , Sun Junyuan , Zhang Qunlei , Zhang Jianwei , He Long , Wang Ziyang , Hu Lei
Published: January 2023

Studies have previously demonstrated that anxious attachment shapes the association between childhood traumatic experiences and somatic pain; however, it remains unclear how this relationship is influenced by anxious attachment in patients with depression. This study investigated how anxious attachment influences the relationship between childhood traumatic experiences and pain symptoms in depressed patients from a social psychological perspective. A total of 139 adult patients with depression participated in this study; the level of depression was assessed by a psychiatric professional. Childhood trauma, pain symptoms, and attachment dimensions were tested by various questionnaires. The moderating role of anxious attachment in the trauma‐pain association was examined using the PROCESS Model 1. Our findings showed that in depressed patients, childhood maltreatment had a significant positive impact on the severity of pain ratings. Moreover, anxious attachment influenced the relationship between childhood trauma and pain symptoms. Our study indicated that anxious attachment is not necessarily a negative outcome for depressed patients; moderate levels of anxious attachment alleviate childhood trauma‐related pain symptoms in individuals with highly traumatic experiences. Understanding the traumatic experiences and attachment styles of depressed patients with pain complaints can help to develop intervention strategies.
Enhancing Diversity and Inclusion in Clinical Trials
Authors: Corneli Amy , Hanlen‐Rosado Emily , McKenna Kevin , Araojo Richardae , Corbett Dawn , Vasisht Kaveeta , Siddiqi Bernadette , Johnson Tesheia , Clark Luther T. , Calvert Sara B.
Published: January 2023

Women and people from most racial and ethnic groups in the United States have historically been under‐represented in clinical trials of investigational medical products. Inadequate representation of these groups may lead to an incomplete understanding of the safety and efficacy of new drugs, devices, biologics, and vaccines, and limit the generalizability of trial findings. As a result, new medical products may not be beneficial to all people who need them, and existing inequities in outcomes among various population groups may remain unchanged or worsen, or new disparities may arise. Although much work has focused on study‐level strategies, research organizations must make systemic changes to how clinical trials are envisioned and implemented to achieve sustainable support for diversity and inclusion in clinical trials. The Clinical Trials Transformation Initiative (CTTI) conducted interviews with leaders at institutions that conduct clinical trials to explore perspectives on organizational‐level practices that promote diversity and inclusion in clinical trials. Leaders described motivations, such as an ethical and moral imperative; organizational practices, such as staff investment and resource allocation; perceived return on investments, such as better science; and deterrents, such as cost and time. The CTTI also convened an expert meeting to discuss the interview findings and provide guidance. We present the interview findings and expert guidance in a framework that describes four key areas—commitment, partnerships, accountability, and resources—on sustaining organizational‐level approaches for improving diversity and inclusion in clinical trials, with the ultimate goal of advancing health equity. Institutions who conduct and support clinical trials should implement organizational‐level approaches to improve equitable access and diverse patient participation in clinical trials.
Cross‐Ancestry Genome‐Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations
Authors: Khor Chiea Chuen , Winter Stefan , Sutiman Natalia , Mürdter Thomas E. , Chen Sylvia , Lim Joanne Siok Liu , Li Zheng , Li Jingmei , Sim Kar Seng , Ganchev Boian , Eccles Diana , Eccles Bryony , Tapper William , Zgheib Nathalie K. , Tfayli Arafat , Ng Raymond Chee Hui , Yap Yoon Sim , Lim Elaine , Wong Mabel , Wong Nan Soon , Ang Peter Cher Siang , Dent Rebecca , Tremmel Roman , Klein Kathrin , Schaeffeler Elke , Zhou Yitian , Lauschke Volker M. , Eichelbaum Michel , Schwab Matthias , Brauch Hiltrud B. , Chowbay Balram , Schroth Werner
Published: January 2023

The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4‐hydroxy‐tamoxifen and endoxifen, whose formation is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo. We performed the first cross‐ancestry genome‐wide association study with well‐characterized patients of European, Middle‐Eastern, and Asian descent (n = 497) to identify genetic factors impacting active and parent metabolite formation. Genome‐wide significant variants were functionally evaluated in an independent liver cohort (n = 149) and in silico. Metabolite prediction models were validated in two independent European breast cancer cohorts (n = 287, n = 189). Within a single 1‐megabase (Mb) region of chromosome 22q13 encompassing the CYP2D6 gene, 589 variants were significantly associated with tamoxifen metabolite concentrations, particularly endoxifen and metabolic ratio (MR) endoxifen/N‐desmethyltamoxifen (minimal P = 5.4E−35 and 2.5E−65, respectively). Previously suggested other loci were not confirmed. Functional analyses revealed 66% of associated, mostly intergenic variants to be significantly correlated with hepatic CYP2D6 activity or expression (ρ = 0.35 to −0.52), and six hotspot regions in the extended 22q13 locus impacting gene regulatory function. Machine learning models based on hotspot variants (n = 12) plus CYP2D6 activity score (AS) increased the explained variability (~ 9%) compared with AS alone, explaining up to 49% (median R2) and 72% of the variability in endoxifen and MR endoxifen/N‐desmethyltamoxifen, respectively. Our findings suggest that the extended CYP2D6 locus at 22q13 is the principal genetic determinant of endoxifen plasma concentration. Long‐distance haplotypes connecting CYP2D6 with adjacent regulatory sites and nongenetic factors may account for the unexplained portion of variability.
Oligodendroglioma metastasizing to cervical lymph node: Rare entity diagnosed on fine‐needle aspiration cytology
Authors: Kataria Sant Prakash , Mahak  , Kumar Sanjay , Singh Gajender , Singh Sunita
Published: January 2023

Extra neural metastasis of central nervous system oligodendroglioma is very rare. Oligodendroglioma is the seventh most frequently occurring neoplasm of central nervous system (CNS) with metastasis outside the CNS. According to literature, presence of metastasis in CNS was most frequently detected in patients of glioblastoma (41.4%), medulloblastoma (26.7%), ependymomas (16.4%), astrocytoma (10.3%) and oligodendroglioma (5.27%). A 38‐year‐old male patient presented with loss of vision and swelling on left side of neck since last 1 week measuring 3 x 2 cm. He was operated for brain tumor 7 years back, which was diagnosed as oligodendroglioma. Ultrasound sonography revealed multiple hypoechoic lymph nodes in bilateral cervical region largest measuring 4.5 x 1.9 cm in left submandibular region. FNA of left submandibular lymph node was done, which revealed deposits of poorly differentiated malignancy. Cell block was prepared for carrying out ancillary studies which showed positivity for glial fibrillary acidic protein (GFAP), S‐100 and negativity for cytokeratin (CK), epithelial membrane antigen (EMA), LCA and progesterone receptor (PR). Based on previous history of oligodendroglioma, cytological and immunohistochemistry (IHC) findings a diagnosis of metastatic oligodendroglioma was made. Metastasis of oligodendroglioma to cervical lymph node should also be considered as one of the differential diagnoses. Diagnosing metastatic CNS tumor is extremely challenging for pathologists. It is essential to have the clinical information of a previous CNS tumor, including the histologic type and immunophenotype. Besides common malignancies of cervical lymph node, we should also think of CNS metastasis so that patient management will be early and proper.
Suitability of cardiac blood, brain tissue, and muscle tissue as alternative matrices for toxicological evaluation in postmortem cases
Authors: Hansen Stine Lund , Nielsen Marie Katrine Klose , Linnet Kristian , Rasmussen Brian Schou
Published: January 2023

Drug concentrations in peripheral blood are often used to evaluate whether death was caused by drug intoxication. In some cases, peripheral blood is not available, and analytical results of alternative matrices should instead be used in the toxicological evaluation. However, reference concentrations of alternative matrices are few, which makes interpretation of results a challenge. In this study, concentrations of selected benzodiazepines, opioids, illicit drugs, and other commonly used drugs in postmortem femoral blood, cardiac blood, brain tissue, and muscle tissue are presented. Alternative matrix‐to‐femoral blood drug concentration ratios and correlations of blood and alternative matrix drug concentrations were calculated to examine which of the investigated alternative matrices were most suited to use for toxicological evaluation in cases where peripheral blood is not available. The results showed that concentrations in cardiac blood, brain tissue, and muscle tissue could be useful in the postmortem evaluation of most of the 19 selected analytes. In most cases, analytes were detected in all the alternative matrices. The median concentration ratios for the selected analytes in brain tissue, cardiac blood, and muscle tissue relative to femoral blood ranged from 0.57 to 3.42, 0.59 to 1.87, and 0.67 to 7.04, respectively. Overall, cardiac blood provided the concentrations most comparable with femoral blood concentrations, indicating that cardiac blood can be useful in cases where femoral blood is not available. However, the measured concentrations should be interpreted with caution.
Reconfiguration of ecohydrology as a sustainability tool for Himalayan waterways
Authors: Kattel Giri R. , Wu Chunying
Published: January 2023

Twenty first century faces unprecedented challenges for the management of global waterways. The Himalayan waterways in Asia are exposed to unpredictable climatic warming together with anthropogenic perturbations caused by population growth, land use change and socio‐economic development. Given the increased public concerns on the Himalayan Mountain development programmes including the hydropower and tourism, there has been a growing need of the use of interdisciplinary scientific approaches to address water resources challenges that the Himalayan region has faced during the 21st century. Ecohydrology is an emerging scientific tool that explores key hydrological processes regulating structure and function of ecosystems, as well as assessing the impact of biological processes on water cycle variables under rapidly changing environment. The International Geosphere‐Biosphere Programme and the International Hydrological Programme hosted by the United Nations Educational, Scientific and Cultural Organization have adopted ecohydrology as a sustainable development tool by linking water resources and poverty eradication and ecosystem restoration, irrigation, energy and sanitation. However, ecohydrology tool needs to be reconfigured for sustainable development of rapidly changing Himalayan waterways. Here we propose the advancement of ecohydrology by developing various integrated frameworks of ecology, hydrology, hydraulics and sociology for resilient waterways in the Asian Himalayas.
The investigation of heat storage efficiency of salt gradient solar pond with and without phase changing materials
Authors: Sogukpinar Haci , Bozkurt Ismail , Genc Zuhal Karagoz , Karakilcik Mehmet
Published: January 2023

In this work, the effect of with and without phase change materials for long‐term heat storage of a salt gradient solar pond was investigated both experimentally and numerically. Some phase change materials, whose thermal values are close to the operating temperature of the solar pond were selected and examined from fatty acids (camphene, decanoic acid, and palmitic acids) and paraffin derivatives (paraffin wax, C20‐C33, and C16‐C28). A series of experimental studies were then performed with phase change temperature, latent heat and thermal stability, a differential scanning calorimetry, and a thermogravimetric analyzer for sheath, decanoic acid, and palmitic acid. The temperature and enthalpy curve of each phase change material was calculated by months and compared to the solar pond and the longest‐term heat storage was determined. Study shows that the maximum efficiency of the solar pond can be achieved with 24.58% Camphene in November and 22.57% Paraffin C20‐C33 in December. Thus, the camphene shows the best longest‐term heat storage performance thanks to its high melting temperature and density and latent fusion heat. It is one of the best suitable options to improve the heat storage performance of solar ponds.
Pore pressure evolution in bed sediment overridden by debris flow: A general formulation
Authors: Zheng Hongchao , Shi Zhenming , Hanley Kevin J. , Zhou Yuanyuan , Hu Xinli
Published: January 2023

Debris flows can grow dramatically in volume and mobility as they override bed sediment due to the reduction in bed friction resistance caused by high pore fluid pressure (PP). However, the mechanisms that control PP evolution in overridden bed sediment are still unclear. Here, a new mathematical model clarifies how diverse styles and magnitudes of PP evolution can result from regulation of the flow diffusion and shear contraction of bed sediment. Normalization of the model equations shows that the propensity for PP generation depends on timescales of PP diffusion and deformation of the bed grains. The PP of saturated bed sediment under immobile conditions is equal to the fluid pressure at the bottom of the flow due to a non‐flux basal boundary. However, the PP of unsaturated bed sediment is lower than that of the overlying flow. PP diffusion from a debris flow into an unsaturated bed increases with the bed’s permeability and water content. The shear deformation behavior changes from undrained to drained with increasing permeability or decreasing shear velocity of the saturated bed sediment, leading to a reduced magnitude of pore pressure. By contrast, the shear deformation transitions from drained to undrained behavior with increasing permeability and water content of unsaturated bed sediment. The entrainment rate and erosion pattern of bed sediment are closely related to the PP evolution and liquefaction ratio of the bed sediment due to Coulomb‐friction shear tractions. Our models can be used to interpret the feedback of PP on the flow momentum during debris flow entrainment.
Proline‐rich polypeptides (Colostrinin®/COLOCO®) modulate BDNF concentration in blood affecting cognitive function in adults: A double‐blind randomized placebo‐controlled study
Authors: Banasiak‐Cieślar Hanna , Wiener Dawid , Kuszczyk Magdalena , Dobrzyńska Katarzyna , Polanowski Antoni
Published: January 2023

Proline‐rich polypeptides (PRPs complex also known as COLOCO®, Colostrinin®) consist of low‐molecular weight peptides ranging up to 10 kDa, isolated from the bovine colostrum obtained up to 48 h postpartum. PRPs have been shown to affect processes involved in inflammation, brain aging, and neurodegeneration. The aim of this study was to investigate the effect of Colostrinin® (COLOCO®) on the cognitive abilities of healthy volunteers in three different age groups using the CANTAB tool in a double‐blind randomized placebo‐controlled study. BDNF serum level was used as a physicochemical marker of improvement of the cognitive skills. Three hundred and sixty‐one healthy volunteers were divided into three study groups aged 18–24, 25–54, and 55–75; each group was then divided into two subgroups which took either placebo or tested lozenge with 120 μg of PRPs for the period of 4 months. The CANTAB battery test was used to measure the efficacy of PRP in the context of cognitive functioning. After the treatment with COLOCO®, we observed differences within MoCA score in the oldest patients, improvement in DMS and drop in PAL scores within the youngest group, drop in RTI and improvement in RVP scores within the middle‐aged group. It was observed that serum BDNF level increased in all study groups which confirms cognitive improvement. In conclusion, we have shown that Colostrinin® exhibits cognitive enhancing effects, probably through the modulation of BDNF concentrations.
Physicochemical and functional properties of the protein–starch interaction in Chinese yam
Authors: Shao Yelin , Jiao Ruize , Wu Yingyin , Xu Fangcheng , Li Yan , Jiang Qiaojun , Zhang Liang , Mao Linchun
Published: January 2023

Protein–starch interaction has an important impact on the properties of starchy foods rich in protein, but the contribution of the interaction to Chinese yam still remains unclear. This study aimed to characterize the physicochemical and functional properties related to the possible interaction between starch and protein in Chinese yam. Differential scanning calorimetry and rapid viscosity analyzer results revealed that the gelatinization temperature increased in protein and starch cross‐linked powder, while the peak viscosity and the setback viscosity decreased. The swelling power and solubility at 80°C and 95°C decreased with increasing protein ratio in the powder. In vitro starch digestibility test indicated that a high protein ratio could rapidly reduce digestible starch, but increase both slowly digestible starch and resistant starch. Protein could act as the physical barrier toward starch against heating and digestion to exert the influence on starch properties. Fourier transform infrared spectroscopy test revealed the interaction between protein and starch. These results revealed the role of protein–starch interaction and provided beneficial information for the utilization of Chinese yam.
Exploring how family carers of a person with dementia manage pre‐death grief: A mixed methods study
Authors: Moore Kirsten J. , Crawley Sophie , Fisher Emily , Cooper Claudia , Vickerstaff Victoria , Sampson Elizabeth L.
Published: January 2023

Objectives

Many family carers of a person with dementia experience pre‐death grief. We aimed to identify strategies that help carers manage pre‐death grief. We hypothesised that emotion and problem focussed styles would be associated with lower, and dysfunctional coping with higher grief intensity.

Methods

Mixed methods observational study using structured and semi‐structured interviews with 150 family carers of people with dementia living at home or in a care home. Most participants were female (77%), caring for a parent (48%) or partner/spouse (47%) with mild (25%), moderate (43%) or severe (32%) dementia. They completed the Marwit‐Meuser Caregiver Grief Inventory Short Form and the Brief Coping Orientation to Problems Experienced (Brief‐COPE) questionnaire. We asked carers to identify strategies used for managing grief. We recorded field notes for 150 interviews and audio‐recorded additional interviews with a sub‐sample of 16 participants.

Results

Correlations indicated that emotion‐oriented coping was associated with lower grief (R = −0.341), and dysfunctional coping with higher grief (R = 0.435), with a small association with problem‐focused strategies (R = −0.109), partly supporting our hypothesis. Our qualitative themes broadly match the three Brief‐COPE styles. Unhelpful strategies of denial and avoidance align with dysfunctional coping strategies. Psychological strategies (including acceptance and humour) and seeking support were consistent with emotion‐focused strategies, but we did not identify a theme relating to problem‐focused strategies.

Conclusion

Most carers identified multiple strategies for processing grief. Carers could readily identify supports and services that they found helpful for managing pre‐death grief, yet current services appear under‐resourced to meet growing demand. (ClinicalTrials.gov ID: NCT03332979).
Evaluation of decision to delivery interval and its effect on feto‐maternal outcomes in Category‐I emergency cesarean section deliveries in Phuentsholing General Hospital, 2020: A retrospective cross‐sectional study
Authors: Dorjey Yeshey , Tshomo Yezer , Wangchuk Dorji , Bhandari Purushottami , Dorji Choki , Pradhan Diptika , Pemo Rinzin
Published: January 2023

Background and Aims

When there is an immediate threat to maternal or fetal life, it is recommended to deliver within 30 min of the decision to have favorable perinatal outcomes. However, there is no data on the delivery intervals for Category‐I emergency cesarean section in Bhutan. The study evaluated the decision to delivery interval (DDI) and its effect on perinatal and maternal outcomes in Category‐I emergency cesarean section.

Methods

A retrospective cross‐sectional study was conducted at the Phuentsholing General Hospital, Bhutan, from January 1, 2020 to December 31, 2020. Mothers who underwent Category‐I emergency cesarean section were included. The demographic variables, patient transfer time, anesthesia time, operation time, DDI, and maternal and perinatal outcomes were recorded in a standard proforma. The data were analyzed using SPSS version 23.

Results

Of 78 Category‐I emergency cesarean sections, only 23 (29.5%) of the cases were able to perform within 30 min of the DDI. The median (interquartile range) DDI was 37 (30–44) min. More time was taken by anesthetists to administer anesthesia (20 [15–8] min). Fetal distress (40, 51.3%) was the commonest indication. The longest DDI was around 39 min for prolonged labor, and the shortest was 26 min for failed instrumental delivery. Over half of the newborns delivered more than 30 min of DDI had low APGAR scores (25, 32.1%) at 1 min and meconium was present (23, 29.5%). Intensive care was required in 11 (14.1%), of which there was 1 (1.3%) neonatal death.

Conclusion

The Category‐I emergency cesarean sections performed within recommended DDI of 30 min were much less. The main delay was due to the longer time taken for the patient transfer and time taken by the anesthetists to administer anesthesia. Perinatal outcomes were favorable when the deliveries were conducted within 30 min of DDI.