bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis
Authors: Panda Sudhasini , Seelan Diravya M , Faisal Shah , Arora Alisha , Luthra Kalpana , Palanichamy Jayanth Kumar , Mohan Anant , Vikram Naval K , Gupta Neeraj Kumar , Ramakrishnan Lakshmy , Singh Archana
Published: September 2022

Diabetes mellitus (DM) alters immune responses and given the rising prevalence of DM in tuberculosis (TB) endemic countries; hyperglycemia can be a potential risk factor for active TB development. However, the impact of hyperglycemia on TB‐specific innate immune response in terms of macrophage functions remains poorly addressed. We assessed macrophage effector functions in uncontrolled DM patients with or without TB infection (PTB+DM and DM), non‐diabetic TB patients (PTB), and non‐diabetic‐uninfected controls. Phagocytic capacity against BCG and surface expression of different pattern recognition receptors (PRRs) (CD11b, CD14, CD206, MARCO, and TLR‐2) were measured via flow cytometry. Effector molecules (ROS and NO) required for bacterial killing were assessed via DCFDA and Griess reaction respectively. A systematic dysregulation in phagocytic capacity with concurrent alterations in the expression pattern of key PRRs (CD11b, MARCO, and CD206) was observed in PTB+DM. These altered PRR expressions were associated with decreased phagocytic capacity of macrophages. Similarly, ROS was aberrantly higher while NO was lower in PTB+DM. These altered macrophage functions were positively correlated with increasing disease severity. Our results highlight several key patterns of immune dysregulation against TB infection under hyperglycemic conditions and highlight a negative impact of hyperglycemia with etiology and progression of TB.
Pd‐Catalyzed MIA‐Directed Acetoxylation of Benzylamines and Computational Study
Authors: Meng Yue‐Ning , Zhao Shi‐Chen , Liu Peng‐Yu , Hu Dianwen , Wang Shuai , He Yu‐Peng , Yu Fang
Published: September 2022

The direct acetoxylation of substituted benzylamines has been accomplished through methoxyiminoacyl (MIA)‐mediated Pd‐catalyzed C−H functionalization. A diverse array of phenylalanine substrates is amenable to this protocol, providing acetoxylation benzylamine derivatives with good to high efficiency. Computational results revealed that HOAc enhanced the stability of Pd−O bond, which obviously accelerate the reductive elimination step of the acetoxylation process.
Cascaded line‐of‐sight channel estimation for reconfigurable intelligent surface aided multi‐user uplink transmissions
Authors: Xu Yicheng , Chu Hongyun , Xu Pingping
Published: September 2022

The reconfigurable intelligent surface (RIS) is capable of remolding the wireless propagation environment, and thus it is assumed as a key technology to enable the potentials of intelligent communications. For the RIS enabled multi‐user systems, channel estimation is rather challenging due to the passivity of the RIS without signal processing capability, where the channel is cascaded of the base station (BS)‐RIS and the RIS‐user equipments (UEs) paths. In this article, we propose an off‐grid channel estimation method for the RIS enabled multi‐user transmissions, exploiting the cascaded sparsity in the UEs‐RIS‐BS channel model. Specifically, we first reveal the cascaded sparsity, that is, the sparsity exists in the hybrid angular domains of UEs‐RIS and RIS‐BS separated channel. Then, we formulate the cascaded channel estimation problem as a semi‐definite program using ‐type atomic norm minimization and extract the channel parameters using subspace resolution technologies. Simulation results show that the proposed channel estimator achieves higher performance compared with the existing art‐of‐states.
Panax ginseng abuse exhibits a pro‐inflammatory effect by activating the NF‐κB pathway
Authors: Deng Wenjun , Liu Hangxiu , Guo Lanping , Liu Yongzhong , Ma Zhaocheng
Published: September 2022

P. ginseng (Panax ginseng C. A. Meyer) is a well‐known traditional medicine that has been used for thousands of years to treat diseases. However, “ginseng abuse syndrome” (GAS) often occurs due to an inappropriate use such as high‐dose or long‐term usage of ginseng; information about what causes GAS and how GAS occurs is still lacking. In this study, the critical components that potentially caused GAS were screened through a step‐by‐step separation strategy, the pro‐inflammatory effects of different extracts on messenger RNA (mRNA) or protein expression levels were evaluated in RAW 264.7 macrophages through quantitative real‐time polymerase chain reaction (qRT‐PCR) or Western blot, respectively. It was found that high‐molecular water‐soluble substances (HWSS) significantly increased the expression of cytokines (cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (iNOS), and interleukin 6 (IL‐6)) and cyclooxygenase 2 (COX‐2) protein; gel filtration chromatography fraction 1 (GFC‐F1) further purified from HWSS showed prominent pro‐inflammatory effects by increasing the transcription of cytokines (COX‐2, iNOS, tumor necrosis factor alpha (TNF‐α), and interleukin 1β (IL‐1β)) as well as the expression of COX‐2 and iNOS protein. Moreover, GFC‐F1 activated nuclear factor‐kappa B (NF‐кB) (p65 and inhibitor of nuclear factor‐kappa B alpha (IκB‐α)) and the p38/MAPK (mitogen‐activated protein kinase) signaling pathways. On the other hand, the inhibitor of the NF‐κB pathway (pyrrolidine dithiocarbamate (PDTC)) reduced GFC‐F1‐induced nitric oxide (NO) production, while the inhibitors of the MAPK pathways did not. Taken together, GFC‐F1 is the potential composition that caused GAS through the production of inflammatory cytokines by activating the NF‐кB pathway.
Source‐to‐sink systems in the Turpan Basin throughout the Jurassic: Constraints from detrital zircon geochronology
Authors: Hao Bin , Xiao Dongsheng , Jin Jikun , Yang Zhanlong , Zhang Jing , Wei Lihua , Tian Feng , Jia Xueli , Yao Zongsen , Liu Zongbao , Zhao Rongsheng
Published: September 2022

Source‐to‐sink system studies in oil fields are especially important for optimizing the favourable oil‐gas areas; however, this basin‐mountain interaction process is particularly complicated in intermontane basins. In this study, detrital zircon U–Pb dating of 8 new and 3 published samples from throughout the Jurassic in the central Turpan Basin (TB) are combined with collected heavy mineral data to investigate the evolution of the source‐to‐sink system and reconstruct the filling process of this intermontane basin from the Lower to Upper Jurassic. Based on the detrital zircon ages and heavy mineral assemblage, the filling rocks mainly weathered from Mesozoic, Palaeozoic and Precambrian volcanic and metamorphic rocks in the Tian Shan (TS) area, and the source‐to‐sink systems in the basin show a clear alteration corresponding to the uplift of the surrounding mountains during the Jurassic. In the Lower Jurassic, the uplifted central and northern TS was the main provenance and shed the most source rocks northward, and the gentle positive relief of the Bogda Mountains (BM), the northern boundary of the TB, was a secondary provenance and provided limited material to the northern area. In the early Middle Jurassic, these provenances did not alter much, but in the later Middle Jurassic, uplift of the western BM began and provided some extreme new source rocks with detrital zircon ages of approximately 159–172 Ma. In the Upper Jurassic, the considerably uplifted BM became the main provenance, while the still gently uplifted central and northern TS became the secondary provenance.
Heterogeneous morphology of the Solomon Sea slab along the New Britain Trench and its dynamic implications from the analysis of seismicity and gravity anomalies
Authors: Gong Wei , Xing Junhui , Xu Chong , Zhang Hao , Liu Yujuan , Chen Wenwen
Published: September 2022

The New Britain‐North Solomon subduction system is located at the convergence boundary between the Indo‐Australian and Pacific plates. In the Cenozoic, the subduction system gradually evolved into a complex system containing the trench, arc, back‐arc basin and oceanic plateau with the subduction and collision of the Ontong Java Plateau, which becomes one of the best places to explore the subduction dynamics. We attempt to illustrate the morphology of the Solomon Sea slab's response to the collision of the Ontong Java Plateau along the New Britain Trench through the hypocentral distribution, focal mechanisms and density structure from the gravity anomalies. According to the hypocenters and focal mechanisms, the focal stress field of the subducted Solomon Sea Plate along the New Britain Trench is analysed and the spatial distribution pattern of the plate is determined. We found that the maximum subduction depth of the Solomon Sea Plate gradually decreases from ~600 to ~400 km and the morphology of the slab changes from the steep‐dipping subduction to slab roll‐back from the Green and Buka Islands to the Bougainville Islands. Indicated by the analysis of seismicity and gravity anomalies, the spatial differences of the subduction pattern in the Solomon Sea Plate along the New Britain Trench are closely correlated with the block of the upper mantle in the Ontong Java oceanic Plateau, which is characterized by a tendency of thickening from NW to SE along the North Solomon Trench.
Robotic lateral oropharyngectomy following diagnostic tonsillectomy is oncologically safe in patients with human papillomavirus‐related squamous cell cancer: Long‐term results
Authors: Siddiq Somiah , Stephen Sarah , Lin Daniel , Fox Hannah , Robinson Max , Paleri Vinidh
Published: September 2022

Introduction

To report the long‐term oncological and functional outcomes of en bloc TORS lateral oropharyngectomy to address the close/involved margin following diagnostic tonsillectomy in HPV‐related SCC of unknown primary.

Material and methods

A single tertiary center observational cohort over a 4‐year period. Primary outcome measures were disease‐specific survival (DSS), overall survival (OS), and PSS NOD (Performance Status Scale‐Normalcy of Diet) scores.

Results

TORS specimens did not evidence residual carcinoma in 93% of patients. Of 14 patients, 50% received surgery alone (median follow‐up 57 months; range 46–96), the remainder surgery and adjuvant therapy (median follow‐up of 58 months; range 51–69) with 100% DSS, OS and no deterioration of PSS NOD scores.

Conclusions

Long‐term oncological outcomes confirm TORS lateral oropharyngectomy alone is an oncologically safe treatment. Due consideration of this approach is warranted to mitigate against the morbidity of adjuvant radiotherapy treatment in this group of patients.
Hysteresis in streamflow‐water table relation provides a new classification system of rainfall‐runoff events
Authors: Gelmini Ylenia , Zuecco Giulia , Zaramella Mattia , Penna Daniele , Borga Marco
Published: September 2022

Rainfall‐runoff event types can be used to better understand the hydrological functioning of catchments. In this study, we propose a framework to characterize and classify runoff events relying on the hysteresis analysis of the relation between streamflow (independent variable) and depth to water table (dependent variable). We evaluated hysteresis for 112 rainfall‐runoff events occurred in the period 2012–2016 in a small forested catchment in the Italian Pre‐Alps. Three main groups of rainfall‐runoff events were identified, each associated with specific hydro‐meteorological characteristics of the events. A first group, identified by a faster response of streamflow compared to the groundwater level (which led to a clockwise hysteretic loop), was characterized by dry antecedent conditions, short rainfall events, low streamflow peaks and small runoff coefficients. A second group had characteristics similar to the first group, that is, faster response of streamflow compared to the groundwater level (clockwise hysteretic loop), but on average displayed a narrower hysteretic loop. A third group, identified by a faster response of the groundwater level compared to streamflow (which led to an anti‐clockwise loop), was characterized by wet antecedent conditions, long rainfall events, high streamflow peaks and large runoff coefficients. Results showed statistically significant differences among the groups, corroborated by an analysis based on environmental tracers (2H and electrical conductivity). This study shows how the analysis of the hysteretic relation between streamflow and depth to water table can be used for grouping rainfall‐runoff events and to better identify the catchment's hydrological response to rainfall inputs.
What is an insolvency proceeding? Gategroup lands in a gated community
Authors: Mokal Riz
Published: September 2022

Many English (and other) restructuring lawyers consider that the scheme of arrangement cannot properly be characterized as an insolvency proceeding for the purposes of certain international instruments for (amongst other things) the allocation of jurisdiction and/or the recognition of proceedings, judgments, and/or orders. This article shows that this view is mistaken. The article examines insolvency as a scalar attribute and a vague concept. It draws out the implications of treating insolvency law functionally as that part of law which responds to the circumstances peculiar to a debtor's insolvency. It considers the nature of insolvency, “pre‐insolvency”, “preventive'”, restructuring, liquidation, and “pre‐pack” proceedings. It shows that proceedings operating under insolvency law in relation to insolvent debtors often operate in identical or materially similar ways in relation to solvent debtors. This is as true of winding‐up, administration, and company voluntary arrangement proceedings under English law as of the scheme of arrangement. This has important implications for the characterization of a proceeding as an insolvency proceeding for relevant purposes. The article outlines the development of the concordat in several civil law jurisdictions, starting with its roots in Justinian's Digest. It traces the development of the composition in England, starting with its status as a voluntary process incapable of binding dissentients, taking in the “protections” granted by the Privy Council and the “bills of conformity” issued by the Court of Chancery, and then considering statutory compositions. It shows how the statutory composition travelled from natural person insolvency law to corporate insolvency law. The artic draws on this analysis and the official reports on key European instruments allocating international jurisdiction in insolvency and “civil and commercial” matters to characterise the scheme of arrangement. The article also assesses the most detailed critique yet of the gategroup judgment of the High Court of England and Wales, which characterized the restructuring plan proceeding as an insolvency proceeding for certain jurisdictional purposes. The critique of this judgment usefully exposes to the sunlight of public scrutiny — at length and independently of the exigencies of any particular litigation — the types of arguments which have been used to resist the conclusion that the scheme is (quite plainly) a judicial composition which constitutes an insolvency proceeding for relevant purposes when deployed in relation to insolvent companies. The article shows that these arguments are unpersuasive.
Minimum wages and restaurant employment for teens and adults in metropolitan and nonmetropolitan areas
Authors: Winters John V.
Published: September 2022

This study estimates effects of minimum wages on individual restaurant employment using the 2005–2019 Current Population Survey (CPS) and a two‐way fixed effects regression model. I examine effects for teens and adults with less than an associate's degree for the entire United States and by metropolitan area status. The results indicate that minimum wages on average decrease restaurant employment for teens and increase restaurant employment for these adults, suggesting that minimum wages induce labor‐labor substitution. However, this pattern is driven by metropolitan areas residents. The estimated coefficient for minimum wages on teen restaurant employment in nonmetropolitan areas is not statistically significant.
Positive parenting, adolescent adjustment, and quality of adolescent diet in nine countries
Authors: Zietz Susannah , Cheng Emily , Lansford Jennifer E. , Deater‐Deckard Kirby , Di Giunta Laura , Dodge Kenneth A. , Gurdal Sevtap , Liu Qin , Long Qian , Oburu Paul , Pastorelli Concetta , Skinner Ann T. , Sorbring Emma , Steinberg Laurence , Tapanya Sombat , Tirado Liliana Maria Uribe , Yotanyamaneewong Saengduean , Alampay Liane Peña , Al‐Hassan Suha M. , Bacchini Dario , Chang Lei , Bornstein Marc H.
Published: September 2022

Introduction

We sought to understand the relation between positive parenting and adolescent diet, whether adolescents' internalizing and externalizing behaviors mediate relations between positive parenting and adolescent diet, and whether the same associations hold for both boys and girls and across cultural groups.

Methods

Adolescents (N = 1334) in 12 cultural groups in nine countries were followed longitudinally from age 12 to 15. We estimated two sets of multiple group structural equation models, one by gender and one by cultural group.

Results

Modeling by gender, our findings suggest a direct effect of positive parenting at age 12 on a higher quality diet at age 15 for males (β = .140; 95% CI: 0.057, 0.229), but an indirect effect of positive parenting at age 12 on a higher quality diet at age 15 by decreasing externalizing behaviors at age 14 for females (β = .011; 95% CI: 0.002, 0.029). Modeling by cultural group, we found no significant direct effect of positive parenting at age 12 on the quality of adolescent diet at age 15. There was a significant negative effect of positive parenting at age 12 on internalizing (β = −.065; 95% CI: −0.119, −0.009) and externalizing at age 14 (β = −.033; 95% CI: −0.086, −0.018).

Conclusions

We founder gender differences in the relations among positive parenting, adolescents' externalizing and internalizing behaviors, and adolescent diet. Our findings indicate that quality of parenting is important not only in promoting adolescent mental health but potentially also in promoting the quality of adolescents' diet.
Vascular elasticity measurement of the great saphenous vein based on optical coherence elastography
Authors: Gao Tianxin , Liu Shuai , Wang Ancong , Tang Xiaoying , Fan Yingwei
Published: September 2022

Vascular elasticity is important in physiological and clinical problems. The mechanical properties of the great saphenous vein (GSV) deserve attention. This research aims to measure the radial elasticity of ex vivo GSV using the optical coherence elasticity (OCE). The finite element model of the phantom is established, the displacement field is calculated, the radial mechanical characteristics of the simulation body are obtained. Furthermore, we performed OCE on seven isolated GSVs. The strain field is obtained by combining the relationship between strain and displacement to obtain the radial elastic modulus of GSVs. In the phantom experiment, the strain of the experimental region of interest is mainly between 0.1 and 0.4, while the simulation result is between 0.06 and 0.40. The radial elastic modulus of GSVs ranged from 3.83 kPa to 7.74 kPa. This study verifies the feasibility of the OCE method for measuring the radial elastic modulus of blood vessels.
Material properties of degradable alloyFe–30Mn–0.6Nand its effect on ferroptosis in synoviocytes
Authors: Yang Tianyu , Hao Shimin , Wang Penghao , Qin Yu , You Guanchao , Shi Yunyi , Yang Boning , Zhang Ao , Guo Lei , Jiang Tianlong
Published: September 2022

Ferroalloy has shown potential as implant materials, but little attention has been paid to their effects on synovial tissue ferroptosis. This study aimed to examine the mechanical properties, degradability and biocompatibility of Fe–30Mn–0.6N alloy and effects of it on synovial tissue ferroptosis. Tensile testing showed that Fe–30Mn–0.6N alloys exhibited tensile strength of 487 ± 18 MPa, yield strength of 221 ± 10 MPa, elongation of 16.9 ± 0.3% and Young's modulus of 37.7 ± 1.3 GPa. In vivo experiments, the cross‐sectional area of the Fe–30Mn–0.6N alloys decreased by 73.32 ± 12.73% after 8 weeks of implantation. The results of scanning electron microscopy (SEM) and surface elemental analysis (EDS) showed that the Fe–30Mn–0.6N alloys had more Ca, O, C and P element deposition (p < .05). After 2, 4 and 8 weeks of implantation, no inflammatory response was observed in peri‐implant synovial tissue of Fe–30Mn–0.6N and Ti–6Al–4V alloys, and Fe–30Mn–0.6N alloys did not affect the expression of the ferroptosis inhibitory gene Glutathione peroxidase 4 (GPX4). Compared with the control group, 30% Fe–30Mn–0.6N alloy extracts did not affect the cell viability (p > .05) in vitro, and intracellular Fe2+and the reactive oxygen species (ROS) was significantly reduced (p < .05). WB and PCR results showed that the 30% extracts increased the protein activity and mRNA expression of GPX4, FTH1 and SLC7A11 in synoviocytes, but had no effect on PTGS2 and p53. It is concluded that Fe–30Mn–0.6N had degradability and biocompatibility in peri‐implant synovial tissue, and did not induce significantly ferroptosis in synoviocytes.
Targeting bacterial biofilms using vancomycin and multivalent cell‐penetrating peptide labeled quantum dots
Authors: Kumar Munish , Pandey Satish Kumar , Lalhall Alisha , Sharma Rohit , Sharma Rohit K. , Wangoo Nishima
Published: September 2022

Bacterial biofilms are highly resilient microbial musters that are difficult to eradicate, driving the development of novel therapeutic strategies. The current study aims to investigate the therapeutic efficacy of cell‐penetrating peptide‐based targeted delivery of vancomycin functionalized quantum dots in eradicating biofilm formation in gram‐positive and gram‐negative bacterial strains. The conjugate was characterized using fluorimetry, UV–visible spectroscopy, gel electrophoresis, and zeta potential. The conjugate was then tested for antimicrobial and antibiofilm activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and it demonstrated excellent antimicrobial as well as antibiofilm activity against all the tested strains. The findings indicated that the conjugate was capable of overcoming bacterial resistance of bacteria in addition to the eradication of biofilms at effective concentrations.
Epigallocatechin‐3‐gallate (EGCG) attenuates inflammatory responses and oxidative stress in lipopolysaccharide (LPS)‐induced endometritis via silent information regulator transcript‐1 (SIRT1)/nucleotide oligomerization domain (NOD)‐like receptor pyrin domain‐containing 3 (NLRP3) pathway
Authors: Di Man , Zhang Qianfeng , Wang Jingjing , Xiao Xifeng , Huang Jianlei , Ma Yuan , Yang Hongya , Li Mao
Published: September 2022

The protective effects of epigallocatechin‐3‐gallate (EGCG) on lipopolysaccharide (LPS)‐induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl‐2, cleaved caspase‐3, silent information regulator transcript‐1 (SIRT1), nucleotide oligomerization domain (NOD)‐like receptor pyrin domain‐containing 3 (NLRP3), apoptosis‐associated speck‐like protein (ASC) and Caspase1 was detected by Western blot and real‐time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS‐induced uterine histopathological changes, MPO activity, pro‐inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.
Relativistic adapted Gaussian basis sets free of variational prolapse of small and medium size for hydrogen through xenon
Authors: Gusmão Eriosvaldo Florentino , Haiduke Roberto Luiz Andrade
Published: September 2022

Two new relativistic adapted Gaussian basis sets of small and medium size are presented for all elements from Hydrogen through Xenon. These sets are free of variational prolapse and were developed with the polynomial generator coordinate Dirac‐Fock method to be used with two finite nuclear models, uniform sphere and Gaussian. The largest basis set errors for electronic configurations from the Aufbau principle are around 10.0 and 4.7 mHartree for the small– and medium–size sets, respectively, which is in accordance with the accuracy level expected in each case. Hence, to our knowledge, these are the smallest prolapse free basis sets developed for these elements.
DTBP‐promoted Passerini‐type reaction of isocyanides with aldehydes: Synthesis of α‐acyloxycarboxamides
Authors: Wang Zhuo , Zhang Yan , Wu Zi‐Han , Zhao Yu‐Long
Published: September 2022

A novel DTBP‐promoted Passerini‐type reaction of isocyanides with two molecular aldehydes has been developed. This reaction is applicable for a wide range of isocyanides and aldehydes and provides an efficient method for the synthesis of α‐acyloxycarboxamides with two identical functional groups in good to high yields in a single step. The experimental results clearly confirmed the role of water and provided a better mechanistic understanding of this reaction.
Dental trainees’ mental health changes, sources of stress, coping strategies, and suggestions for mental health improvement 1 year into the pandemic
Authors: Hill Courtney M. , Moore Eliza , Randall Cameron L. , Chi Donald L.
Published: September 2022

Objectives

The goal of this study was to assess how the mental health of dental trainees has changed during the pandemic and to identify the most stressful aspects of trainees’ programs, stress coping strategies, and suggestions for individual and institution‐driven solutions to improve wellness.

Methods

The study focused on dental trainees at the University of Washington who completed a wellness survey in fall 2020 (n = 126; response rate = 35.5%) and spring 2021 (n = 105; response rate = 29.6%). The survey included self‐report measures assessing four mental health outcomes: depression, anxiety, isolation from peers, and burnout. Stressful aspects of the training program, coping strategies, and institution‐driven solutions were measured with open‐ended survey items. The chi‐square test was used to compare mental health outcome measures between fall and spring and open‐ended survey responses were inductively coded.

Results

The prevalence of self‐reported depression and anxiety did not change between fall 2020 and spring 2021 (17.2% vs. 21.1%, p = 0.473; 22.4% vs. 23.7%, p = 0.818). Isolation from peers and burnout each significantly increased by almost 20% from fall 2020 to spring 2021 (46.8% vs. 64.3%; p = 0.009 and 26.6% vs. 43.9%; p = 0.017). Trainees identified workload as the most stressful aspect of their program and described using exercise and social support to cope with stress. Trainees suggested institution‐supported increases in social events and mental health resources.

Conclusions

One year into the coronavirus disease 2019 pandemic, poor mental health outcomes were common among dental trainees because of high workload and isolation from peers. Dental schools should promote targeted programs and services aimed at improving dental trainees' well‐being.
Managing relapsed refractory lymphoma with palliative oral chemotherapy: A multicentre retrospective study
Authors: Bulley Simon J. , Santarsieri Anna , Lentell Isabel C. , O'Sullivan Brendan , Hodson Andrew , Firth Oliver , Sadullah Shalal , Follows Annabel M. , Karanth Mamatha , Min Sandra Young , Fowler Alexis , Russell James , Uttenthal Benjamin J. , Hodson Daniel J. , Follows George A.
Published: September 2022

PEP‐C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP‐C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP‐C in 92 patients over an 8‐year period. We find that even heavily pretreated lymphoma can respond to PEP‐C, particularly low‐grade lymphoma (including mantle cell) and lymphoma that was sensitive to the previous line of systemic therapy (chemosensitive). These characteristics may help in the selection of patients likely to derive benefit. The median overall survival of patients with chemosensitive lymphoma treated with PEP‐C is 217 days. Within the limitations of a retrospective cohort, we find that PEP‐C is well tolerated: the most common toxicity leading to discontinuation is marrow suppression. We suggest that PEP‐C should be considered for patients with relapsed refractory lymphoma in two settings: first, where there is no licensed alternative; and second, where the licensed alternative is an intravenous drug and the patient would prefer to choose an oral chemotherapy option.
Neutralizing monoclonal antibodies for early treatment of hospital‐acquired SARS‐CoV‐2 infection in hematologic patients
Authors: Bussini Linda , Testi Diletta , Tazza Beatrice , Oltolini Chiara , Mastaglio Sara , Sepulcri Chiara , Campoli Caterina , Trapani Filippo , Pasquini Zeno , Zappulo Emanuela , Bassetti Matteo , Viale Pierluigi , Mikulska Malgorzata , Bartoletti Michele
Published: September 2022

Efficacy of early treatment with anti‐SARS‐CoV‐2 spike protein monoclonal antibodies (mAbs) for nosocomial SARS‐CoV‐2 infection in hematologic patients is unknown. Retrospective, cohort study conducted in four Italian teaching hospitals. We included adult patients with hematologic malignancies and hospital‐acquired SARS‐CoV‐2 infection diagnosed between November 2020 and December 2021. The principal exposure variable was administration of mAbs. The primary endpoint was clinical failure dea composite outcome of mortality and/or invasive and noninvasive ventilation within 90 days from infection onset. We included 52 patients with hospital‐acquired SARS‐CoV‐2 infection. Males were 29 (60%), median age was 62 (interquartile range [IQR] 48–70). Forty‐five (86%) patients were on chemotherapy or had received chemotherapy within 30 days. MAbs were administered in 19/52 (36%) patients. Clinical failure occurred in 22 (42%) patients; 21% (4/19) in mAbs group versus 54% (18/33) in non‐mAbs group (p = 0.03). Other predictors of clinical failure were older age (median [IQR] 69 [61–72] versus 58 [46–66], p = 0.001), and higher Charlson comorbidity index (median [IQR], 5 [3.25‐5] versus 3 [2–5], p = 0.002). At multivariable Cox regression model, mAbs were independently associated with a significantly lower rate of clinical failure (HR 0.11, 95% CI 0.01–0.85, p = 0.01), after adjusting for confounders. In conclusion, mAbs are promising for early treatment of hematologic patients with healthcare‐related SARS‐CoV‐2 infection.
A germline exome analysis reveals harmful POT1 variants in multiple myeloma patients and families
Authors: Hakkarainen Marja , Koski Jessica R. , Heckman Caroline A. , Anttila Pekka , Silvennoinen Raija , Lievonen Juha , Kilpivaara Outi , Wartiovaara‐Kautto Ulla
Published: September 2022

Observations of inherited susceptibility to multiple myeloma have led to active research in defining predisposing genes to the disease. Here, we analysed 128 plasma cell dyscrasia patients’ germline whole‐exome sequencing data. Rare dominantly inherited pathogenic or likely pathogenic (P/LP) variant was found in 9.4% of the patients. Among the P/LP variants, CHEK2 (p. Thr410MetfsTer15) was the most prevalent (n = 5, 3.9%). Interestingly, P/LP variants in POT1 were identified in three patients (2.3%). Our findings broaden the spectrum of POT1‐related cancers and demonstrate the importance of the germline genetic analysis in hematological malignancies.
β‐Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy
Authors: Pedersen Jonas Jalili , Duno Morten , Wibrand Flemming , Hammer Christian , Krag Thomas , Vissing John
Published: September 2022

Deficiency of the enzyme β‐galactosidase due to variants in the GLB1‐gene is associated with metabolic disorders: Morquio B and GM1‐gangliosidosis. Here, we report a case compound heterozygous for variants in the GLB1‐gene and a severe muscular phenotype. Full body T1‐w MRI was conducted for muscular involvement. Biopsy was stained with hematoxylin and eosin for histopathological evaluation. EDTA blood‐sample was subjected to whole exome sequencing. Metabolic analysis included residual enzyme activity and evaluation urinary substrate secretion. Additionally, electroneurography, echocardiography, forced volume capacity and biochemistry were evaluated. Examination showed severe proximal weakness (MRC: hip flexion 2, hip extension 2, and shoulder rotation 2), Gower's sign, no extrapyramidal symptoms and normal creatine kinase levels. MRI showed severe muscle wasting of the thigh and shoulder girdle. Muscle biopsy showed mild myopathic changes. β‐galactosidase activity was reduced to 28%–34%. Urinary glycosaminoglycan was elevated by 5.9–8.6 mg/mmol (ref.:0–5.1 mg/mmol). Electrophoresis indicated excess keratan sulfate. Exome sequencing revealed two missense variants in the GLB1 gene. Clinical features, genetic testing and laboratory findings indicate a case of β‐galactosidase‐deficiency with a muscular phenotype.
Interactions between the Caspian Sea size (level) and atmospheric circulation
Authors: Molavi‐Arabshahi Mahboubeh , Arpe Klaus
Published: September 2022

Results from idealized model simulations (a relationship between Caspian Sea level [CSL] with its change of the Caspian Sea [CS] size and CS surface temperature [SST]) are validated and connections are explained. Energy budgets for CS water using proxy observational data (ERA5) are used, especially for the comparison of 1979 and 1995, the two extreme values of the CSL. In 1995, when CSL reached a maximum, there were many El Niño events. Investigations on the effects of ENSO on the position of the jet stream over the CS had previously been shown. A jet stream requires a region of baroclinicity beneath it, usually associated with precipitation and cloud cover. This leads to an increase in CSL. A possible forcing of El Niño events by the CS size was found in recent idealized model simulations. Evidence of this is also documented here in analysis of observational data. The size of the CS could have an impact on the occurrence of El Niño events that affect atmospheric circulation. There is much evidence of such a relationship in the observed atmosphere. Real proof is extremely difficult to obtain, only one historical event provides further evidence for such a connection.
A high‐performance liquid chromatography method for simultaneous quantification of metformin and ferulic acid in solid dosage forms
Authors: Chaves Júnior José Venâncio , Muniz Vanessa Morais , de Almeida Vinícius Cleithon Rodrigues , de Souza Fábio Santos , Aragão Cícero Flávio Soares
Published: September 2022

Metformin is one of the most commonly used drugs in the world for the treatment of type 2 diabetes, while ferulic acid is a molecule that stands out for its antioxidant potential. Recent studies demonstrate hypoglycemic synergy between these molecules. The objective of this study is to develop and validate an analytical methodology by high‐performance liquid chromatography for the simultaneous quantification of these drugs in pharmaceutical formulations. The method used an octadecylsilane column and a mobile phase composed of 6 mM sodium lauryl sulfate in 15 mM phosphate buffer:ACN (65:35). Ferulic acid and metformin were monitored at 232 nm, with a mobile phase flow rate of 1 ml/min and oven temperature at 40°C. The method was linear in the range of 5–25 μg/ml for both molecules. In the presence of degradation products, satisfactory selectivity was achieved. Accuracy values were close to 100% and standard deviations in precision were less than 2%. In the robustness evaluation, the proposed variations did not interfere with the quantification. Therefore, it is concluded that the present method can be safely applied to the quality control of ferulic acid and metformin raw materials, as well as when they are combined in pharmaceutical formulations.
Utilization of ionic deep eutectic solvent as sustainable mobile phase additive in high‐performance liquid chromatography for improving the separation of biogenic amines
Authors: He Sile , Choi Dong Min , Row Kyung Ho
Published: September 2022

Biogenic amines are present in large quantities in fermented foods and are a key marker for assessing food safety. This paper proposes a novel method for high‐performance liquid chromatography analysis of biogenic amines using deep eutectic solvent as a mobile phase additive. After screening eight synthetic deep eutectic solvents and comparing them with several common additives, deep eutectic solvents based on choline chloride and ethylene glycol showed significant effects in improving the separation of biogenic amines. A Box–Behnken design of 17 runs was used to screen and optimize the key chromatographic parameters, resulting in an expected composition of the mobile phase of 0.73% deep eutectic solvent, 65% acetonitrile, and a column temperature of 28°C. The proposed method exhibited excellent linearity (0.1–50 μg/ml, R2 ≥ 0.9987), limit of detection (0.007–0.031 μg/ml), precision (1.28%–5.34%) and accuracy (87.2%–110.6%). The method can be applied successfully to the separation and analysis of biogenic amines in cooking wine samples.
The effect of global volatility, uncertainty and geopolitical risk factors on international tourist arrivals in Asia
Authors: Doğan Buhari , Ghosh Sudeshna , Tiwari Aviral Kumar , Abakah Emmanuel Joel Aikins
Published: September 2022

The major tourist destinations in the Asian region are promoting and maintaining a conducive tourism environment. The susceptibility of the major tourist destinations in Asia to the uncertainties may encumber the arrival of international tourists. However, to the best of our understanding the research in this area is scant. Further though the tourism‐uncertainty nexus has been widely explored in the literature, the deliberations in a time‐varying and frequency‐domain framework continue to be ignored. Thus, building upon the earlier deficiencies this study, investigates in a time and scale varying framework the tourism uncertainty/risk nexus for Singapore and Malaysia, two major tourist destinations in the Asian region. This article endeavors to investigate the role of world policy uncertainty, US Monetary Policy Uncertainty, geopolitical risk, Global Financial Stress Index and market volatility on international tourist arrivals in Malaysia and Singapore. To the best of our understanding, this study is the foremost to scrutinize the interrelatedness between these variables in a multivariate wavelet causality framework, from January 2000 to April 2020. Our results show that the global uncertainties manifested through different macro‐based indicators affect international tourism demand for the destination countries. During the subprime crisis, Euro‐crisis and the pandemics significant coherencies are perceptible. The major empirical findings of the impact of uncertainty indicators and geopolitical risk on international tourist arrivals over the recent period have important implications for policy makers and practitioners.
Movement of white‐tailed deer in contrasting landscapes influences management of chronic wasting disease
Authors: Jennelle Christopher S. , Walter W. David , Crawford Joanne , Rosenberry Christopher S. , Wallingford Bret D.
Published: September 2022

Chronic wasting disease (CWD) continues to expand in distribution and prevalence across North America. Upon detection, either for the first time in a novel area or in a region with an existing outbreak, wildlife management agencies are tasked with responding to mitigate the disease. This response often entails creation or modification of a management zone with modified rules and regulations that support an agency's disease management plan. To guide the process of creating an appropriately sized CWD management zone, assuming that wild deer movements are a major risk factor for disease spread, we used data from global positioning system (GPS)‐collared white‐tailed deer (Odocoileus virginianus) in southeastern Minnesota and southcentral Pennsylvania, USA, between 2018 and 2021 to estimate long‐distance movements associated with dispersal and migratory behaviors. These contrasting study areas with active CWD outbreaks permitted an evaluation of deer movement dynamics in different parts of their range. We quantified the proportion, distribution, timing, and orientation of dispersing and migratory deer. We observed 21% of female and 58% of male yearlings disperse from their apparent natal home range in Minnesota, while in Pennsylvania 4% of female and 68% of male yearlings dispersed. We also documented 20% of females and 6% of males migrated between seasonal home ranges in Minnesota, while in Pennsylvania no females and 5% of males migrated. The average distance deer dispersed or migrated in Minnesota was 20 km and 11 km, respectively, while in Pennsylvania male deer dispersed only about 4 km. Both sexes in Minnesota tended to disperse in a consistent, westerly direction; however, there was no directional preference observed for migratory deer or for dispersing deer in Pennsylvania. We found differences between natal and adult home range size for both sexes in Minnesota but not for males in Pennsylvania. Our results identify the considerable variability in dispersal and migration dynamics of white‐tailed deer in disparate landscapes, which is important to agencies managing CWD. We summarize the distribution of these movements and suggest agencies use this information to help make decisions about optimal management zone size. We suggest the development of formalized assessments of the tradeoffs associated with optimizing decisions about creation of CWD management zones across white‐tailed deer populations that exhibit variation in dispersal behavior and suggest careful evaluation to avoid using an arbitrary size or shape to create disease management zones.
Generation of predictive models for oxidative degradation kinetics of dapagliflozin with the applications of DOE and stability indicating HPLC method
Authors: Bodiwala Kunjan B. , Shah Jaldhi , Sureja Dipen K. , Dhameliya Tejas M. , Khadela Avinash
Published: September 2022

Applying kinetics principles to drug degradation studies helps in determine the expiration dates of drugs and formulations. An accurate, precise and sensitive stability‐indicating high‐performance liquid chromatographic method was developed and validated to study the degradation kinetics of Dapagliflozin (DGZ). DGZ was degraded under different stress conditions and degraded samples were chromatographed on C18 (150 mm × 4.6 mm, 5 µm) column, separated using solvent system acetonitrile and 0.01% triethylamine solution (pH 5 adjusted with orthophosphoric acid) in a ratio of 70:30 v/v and detected at 270 nm. The design of experiments (DOEs) was applied to study the degradation kinetics of DGZ in the oxidative medium. The effect of temperature and concentration of H2O2 on the order of reaction and % degradation was studied at three levels using a full factorial design. The linearity range for DGZ was 1–60 µg/mL (correlation coefficient = 0.9996) with an average recovery of 99.98%. The limit of detection (LOD) and limit of quantitation (LOQ) for DGZ were 0.07 and 0.22 µg/mL, respectively. Degradation of DGZ in the oxidative medium was found to follow first‐order kinetics. Contour plots have been generated to predict the degradation rate constant and % degradation of DGZ in different combinations of temperature and concentration of H2O2 using Design Expert software (Trial version).
Wetland ecosystem health improvement from ecological conservation and restoration offset the decline from socio‐economic development
Authors: Liu Weiwei , Cui Lijuan , Guo Ziliang , Wang Daan , Zhang Manyin
Published: September 2022

In response to wetland degradation due to socio‐economic development, attention to ecological conservation and restoration is increasing globally. In China, more than 1100 wetland conservation and restoration projects were implemented over the past decade. However, the net effects of socio‐economic development and ecological conservation and restoration on ecosystem health have received little empirical examination. We analyzed the spatial–temporal dynamics of ecosystem health in Hengshui Lake Wetland Nature Reserve in northern China, and demonstrated the dual effect of the above‐mentioned factors on ecosystem health. The results indicated that ecosystem health increase due to conservation and restoration offset the decrease due to socio‐economic development, which resulted in a significant increase in the net value by 34.6% over the past 19 years. Wetland conservation and restoration dominated ecosystem health improvement in most study regions, while population growth determined the decrease in ecosystem health in residential regions and transportation land, thus intensifying the spatial heterogeneity. Crucially, targeted and practical conservation strategies have been provided according to the low index and regions, together with its main driving factors. The net effects, spatial heterogeneity and management strategies revealed by this case‐study provide critical implications for large‐scale wetland ecosystems that are pervasive degradation induced by socio‐economic development.
Fostering the use of Learning Health Systems through a fellowship program for interprofessional clinicians
Authors: Dushyanthen Sathana , Perrier Meg , Chapman Wendy , Layton Meredith , Lyons Kayley
Published: September 2022

Introduction

To address Australian workforce needs, we developed a Learning Healthcare System (LHS) Academy fellowship program for clinicians. In the Academy, fellows complete foundational coursework, an LHS project, and other professional development deliverables to foster their future as digital health champions within their organizations. In this paper, we describe the 11‐month‐long program, as well as our evaluation results from the first 2 months of the program.

Methods

In the first week of the program, we sent all fellows an open‐ended survey asking fellows to describe their digital health professional identities and what they expected to achieve from the fellowship program. At 2 months, we sent a follow‐up open‐ended survey that captured identical measures, their perceived barriers to participation in the program, perceived use of topics in the workplace and to their projects, and recommendations for program improvement. We analyzed the open text responses using qualitative content analysis, to identify categories of responses.

Results

Overall, 2 months into the program, it was evident that participants were finding the teaching model engaging, useful, valuable, and applicable to their work and projects. Fellows perceived barriers to engagement in the program as balancing other commitments, lacking technical expertise, and having difficulty seeing themselves as leaders. Fellows expected that the program will allow them to implement new models of care, provide them with enough expertise to become leaders and champions in digital health, and become mentors for future generations. As far as changes in their professional identity, there was a notable increase in the number of fellows perceiving themselves as leaders.

Conclusion

Fellowship programs are one promising means of developing the healthcare workforce in LHS capabilities. Future studies should describe and evaluate LHS programs, to provide insights and recommendations for other educators interested in implementing similar programs of work within their own institutions.