bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of a Peer Mentoring Circle: An Innovation to Improve Academic Physician Career Advancement in a Community Hospital Setting
Authors: Kaushik Ruchi , McCallin Tracy , Sedillo Daniel J. , Wolfe Adam D.
Published: December 2022

Problem

Faculty retention is a prominent topic in academic medicine. Investment in faculty career development supports faculty vitality, advancement, and retention. Academic physicians in community-based settings far from their academic affiliate may find identifying local career advancement mentorship challenging.

Approach

In June 2018, a career advancement in-service day at The Children’s Hospital of San Antonio and Baylor College of Medicine in Houston was convened to design a peer mentoring circle (PMC). Using self-determination theory, this program aimed to help PMC members develop goals; schedule and attend regular meetings; format, review, and critique member curricula vitae and portfolios; and hold one another accountable to submitting award and promotion applications.

Outcomes

Eleven inaugural PMC cohort members attended regular monthly meetings from July 2018 to June 2019 (median, 6 members per meeting). All members were competent in accessing the PMC repository of materials. Statistically significant improvement (P < .01) was seen in self-reported knowledge and skills relevant to award or academic promotion support and resources. Compared with no patient care or teaching awards and 1 academic promotion among non-PMC faculty, 5 PMC members (45.5%) earned a patient care award, 4 (36.4%) earned a teaching award, and 5 of 10 faculty members (50.0%) achieved academic promotion (P < .001 for all). On the retrospective pre–post survey, members endorsed several PMC strengths, including personal and emotional support, professional support, and accountability.

Next Steps

Next steps include establishing a local faculty development office, convening a second cohort, revising evaluation methods, expanding membership, and offering 1-on-1 career counseling. Community-based academicians who aim to replicate this program should organize a career advancement and faculty development in-service day, identify local faculty members to manage meetings, retain a repository of resources, set deadlines and hold one another accountable to them, and celebrate achievements and support one another in failure.
Respiratory Effects of Biased Ligand Oliceridine in Older Volunteers: A Pharmacokinetic–Pharmacodynamic Comparison with Morphine
Authors: Simons Pieter , van der Schrier Rutger , van Lemmen Maarten , Jansen Simone , Kuijpers Kiki W.K. , van Velzen Monique , Sarton Elise , Nicklas Todd , Michalsky Cathy , Demitrack Mark A. , Fossler Michael , Olofsen Erik , Niesters Marieke , Dahan Albert
Published: December 2022

Background

Oliceridine is a G protein–biased µ-opioid, a drug class that is associated with less respiratory depression than nonbiased opioids, such as morphine. The authors quantified the respiratory effects of oliceridine and morphine in elderly volunteers. The authors hypothesized that these opioids differ in their pharmacodynamic behavior, measured as effect on ventilation at an extrapolated end-tidal Pco
2 at 55 mmHg, V̇E55.

Methods

This four-arm double-blind, randomized, crossover study examined the respiratory effects of intravenous 0.5 or 2 mg oliceridine and 2 or 8 mg morphine in 18 healthy male and female volunteers, aged 55 to 89 yr, on four separate occasions. Participants’ CYP2D6 genotypes were determined, hypercapnic ventilatory responses were obtained, and arterial blood samples were collected before and for 6 h after treatment. A population pharmacokinetic–pharmacodynamic analysis was performed on V̇E55, the primary endpoint; values reported are median ± standard error of the estimate.

Results

Oliceridine at low dose was devoid of significant respiratory effects. High-dose oliceridine and both morphine doses caused a rapid onset of respiratory depression with peak effects occurring at 0.5 to 1 h after opioid dosing. After peak effect, compared with morphine, respiratory depression induced by oliceridine returned faster to baseline. The effect-site concentrations causing a 50% depression of V̇E55 were 29.9 ± 3.5 ng/ml (oliceridine) and 21.5 ± 4.6 ng/ml (morphine), the blood effect-site equilibration half-lives differed by a factor of 5: oliceridine 44.3 ± 6.1 min and morphine 214 ± 27 min. Three poor CYP2D6 oliceridine metabolizers exhibited a significant difference in oliceridine clearance by about 50%, causing higher oliceridine plasma concentrations after both low- and high-dose oliceridine, compared with the other participants.

Conclusions

Oliceridine and morphine differ in their respiratory pharmacodynamics with a more rapid onset and offset of respiratory depression for oliceridine and a smaller magnitude of respiratory depression over time.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Extended-age Out-of-sample Validation of Risk Stratification Index 3.0 Models Using Commercial All-payer Claims
Authors: Greenwald Scott , Chamoun George F. , Chamoun Nassib G. , Clain David , Hong Zhenyu , Jordan Richard , Manberg Paul J. , Maheshwari Kamal , Sessler Daniel I.
Published: December 2022

Background

The authors previously reported a broad suite of individualized Risk Stratification Index 3.0 (Health Data Analytics Institute, Inc., USA) models for various meaningful outcomes in patients admitted to a hospital for medical or surgical reasons. The models used International Classification of Diseases, Tenth Revision, trajectories and were restricted to information available at hospital admission, including coding history in the previous year. The models were developed and validated in Medicare patients, mostly age 65 yr or older. The authors sought to determine how well their models predict utilization outcomes and adverse events in younger and healthier populations.

Methods

The authors’ analysis was based on All Payer Claims for surgical and medical hospital admissions from Utah and Oregon. Endpoints included unplanned hospital admissions, in-hospital mortality, acute kidney injury, sepsis, pneumonia, respiratory failure, and a composite of major cardiac complications. They prospectively applied previously developed Risk Stratification Index 3.0 models to the younger and healthier 2017 Utah and Oregon state populations and compared the results to their previous out-of-sample Medicare validation analysis.

Results

In the Utah dataset, there were 55,109 All Payer Claims admissions across 40,710 patients. In the Oregon dataset, there were 21,213 admissions from 16,951 patients. Model performance on the two state datasets was similar or better than in Medicare patients, with an average area under the curve of 0.83 (0.71 to 0.91). Model calibration was reasonable with an R
2 of 0.93 (0.84 to 0.97) for Utah and 0.85 (0.71 to 0.91) for Oregon. The mean sensitivity for the highest 5% risk population was 28% (17 to 44) for Utah and 37% (20 to 56) for Oregon.

Conclusions

Predictive analytical modeling based on administrative claims history provides individualized risk profiles at hospital admission that may help guide patient management. Similar predictive performance in Medicare and in younger and healthier populations indicates that Risk Stratification Index 3.0 models are valid across a broad range of adult hospital admissions.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Noise Reduction for Magnetic Resonance Imaging by Using Edge Detection and Hybrid Mean Lee Filter Techniques
Authors: Mustafa Zeinab A. , Ibraheem Banazier A. , GissmAllah Kawther M. , Elmahdi Rania E. , Omara Akram I.
Published: December 2022

In this article, spatial-domain filtering algorithms were developed to suppress additive noise in magnetic resonance (MR) imaging. It is difficult to suppress MR image noise because it corrupts almost all pixels in an image. The purpose of noise reduction is to curb the noise with high efficiency while keeping the edges and other detailed features as much as possible. The present article focused on developing quite efficient noise reduction by using an edge detection technique and hybrid mean Lee filters to suppress MR image noise quite effectively in spatial domain without yielding much distortion and blurring. The performances of the developed filter were compared with the existing filters in terms of universal quality index, method noise, and execution time. Among all existing filters, the edge detection technique and hybrid mean Lee filter was found to be best for suppressing MR image noise.
Prevalence of Unhealthy Substance Use and Associated Characteristics Among Patients Presenting for Surgery
Authors: Fernandez Anne C. , Waljee Jennifer F. , Gunaseelan Vidhya , Brummett Chad M. , Englesbe Michael J. , Bicket Mark C.
Published: December 2022

Objective:

To assess the prevalence of and identify characteristics associated with unhealthy use before surgery.

Background:

Although the escalation in US drug overdose deaths is apparent, the unhealthy use of substances among patients presenting for surgery is unclear.

Methods:

We conducted a retrospective study of patients presenting for elective surgical procedures between December 2018 and July 2021 and prospectively recruited to 1 of 2 clinical research studies (Michigan Genomics Initiative, Prevention of Iatrogenic Opioid Dependence after Surgery Study). The primary outcome was unhealthy substance use in the past 12 months as determined using the Tobacco, Alcohol, Prescription medication, and other Substance use tool.

Results:

Among 1912 patients, unhealthy substance use was reported in 768 (40.2%). The most common substances with unhealthy use were illicit drugs [385 (20.1%)], followed by alcohol 358 (18.7%)], tobacco [262 (13.7%)], and prescription medications [86 (4.5%)]. Patients reporting unhealthy substance use were significantly more likely to be younger, male [aOR: 1.95 (95% CI, 1.58–2.42)], and have higher scores for pain [aOR: 1.07 (95% CI, 1.02–1.13)], and anxiety [aOR: 1.03 (95% CI, 1.01–1.04)]. Unhealthy substance use was more common among surgical procedures of the forearm, wrist, and hand [aOR: 2.58 (95% CI, 1.01–6.55)].

Conclusions:

As many as 2 in 5 patients in the preoperative period may present with unhealthy substance use before elective surgery. Given the potential impact of substance use on surgical outcomes, increased recognition of the problem by screening patients is a critical next step for surgeons and perioperative care teams.
Characterizing the Impact of Procedure Funding on the Covid-19 Generated Procedure Gap in Ontario: A Population-Based Analysis
Authors: Gomez David , de Mestral Charles , Stukel Therese A. , Irish Jonathan , Simpson Andrea N. , Wilton Andrew S. , Rotstein Ori D. , Campbell Robert J. , Eskander Antoine , Urbach David R. , Baxter Nancy N.
Published: December 2022

Background:

Surgical procedures in Canada were historically funded through global hospital budgets. Activity-based funding models were developed to improve access, equity, timeliness, and value of care for priority areas. COVID-19 upended health priorities and resulted in unprecedented disruptions to surgical care, which created a significant procedure gap. We hypothesized that activity-based funding models influenced the magnitude and trajectory of this procedure gap.

Methods:

Population-based analysis of procedure rates comparing the pandemic (March 1, 2020–December 31, 2021) to a prepandemic baseline (January 1, 2017–February 29, 2020) in Ontario, Canada. Poisson generalized estimating equation models were used to predict expected rates in the pandemic based on the prepandemic baseline. Analyses were stratified by procedure type (outpatient, inpatient), body region, and funding category (activity-based funding programs vs. global budget).

Results:

In all, 281,328 fewer scheduled procedures were performed during the COVID-19 period compared with the prepandemic baseline (Rate Ratio 0.78; 95% CI 0.77–0.80). Inpatient procedures saw a larger reduction (24.8%) in volume compared with outpatient procedures (20.5%). An increase in the proportion of procedures funded through activity-based programs was seen during the pandemic (52%) relative to the prepandemic baseline (50%). Body systems funded predominantly through global hospital budgets (eg, gynecology, otologic surgery) saw the least months at or above baseline volumes, whereas those with multiple activity-based funding options (eg, musculoskeletal, abdominal) saw the most months at or above baseline volumes.

Conclusions:

Those needing procedures funded through global hospital budgets may have been disproportionately disadvantaged by pandemic-related health care disruptions.
What Have We Learned From In Vitro Studies About Pig-to-primate Organ Transplantation?
Authors: Hara Hidetaka , Yamamoto Takayuki , Wei Hong-Jiang , Cooper David K.C.
Published: December 2022

Natural preformed and de novo antibodies against pig antigens are a major cause of pig xenograft rejection in nonhuman primates (NHPs). In vivo studies in pig-to-NHP models are time consuming. In vitro assays, for example, antibody binding to pig cells, complement-dependent cytotoxicity assays, provide valuable information quickly and inexpensively. Using in vitro assays for several years, it has been documented that (1) during the first year of life, humans and NHPs develop anti–wild-type pig antibodies, but humans develop no or minimal antibody to triple-knockout (TKO) pig cells. (2) Some adult humans have no or minimal antibodies to TKO pig cells and are therefore unlikely to rapidly reject a TKO organ, particularly if the organ also expresses human “protective” proteins. (3) There is good correlation between immunoglobulin (Ig)M (but not IgG) binding and complement injury. (4) All Old World NHPs develop antibodies to TKO pig cells and are not optimal recipients of TKO organs. (5) galactosyltransferase gene-knockout/β4GalNT2KO pigs are preferred for Old World NHPs. (6) Humans develop anti-pig IgE and IgA antibodies against pig cells, but their role remains uncertain. (7) In a small percentage of allosensitized humans, antibodies that cross-react with swine leukocyte antigens may be detrimental to a pig organ xenograft. (8) Prior sensitization to pig antigens is unlikely to be detrimental to a subsequent allograft. (9) Deletion of expression of Gal and Neu5Gc is associated with a reduction in the T-cell response to pig cells. All of these valuable observations have largely predicted the results of in vivo studies.
Acute hemorrhagic necrotizing encephalopathy associated with COVID-19 in a patient with liver cirrhosis
Authors: Singh Sweta , Singh Uday Shanker
Published: December 2022

COVID-19 emerging as a global pandemic is a complex disease presenting with multiorgan involvement.AHNE is a rarely reported phenomenon post COVID-19 infection but is a rapidly progressing, fatal, haemorrhagic necrosis of the CNS parenchyma. Here,we present a very interesting case of a cirrhotic male patient with acute hemorraghic necrotizing encephalopathy with COVID-19 infection. Diagnosis of AHNE requires a multimodality approach and high index of suspicion in a patient suffering from SARS CoV-2.Timely intervention and diagnosis may lead to a favourable outcome in the diagnosed cases.Future detailed studies in this direction may give an insight on this rare but important disease entity.
Evaluation of Triglyceride-Glucose Index as a Marker for Severity in New Onset Diabetes in Patients of COVID-19 Pneumonia- a Single Center Study
Authors: Ashraf Faiza , Mehmood Majid , Aurang Zeb Mohammad , Rehman Jehanzeb ur , Siddiqui Fariha Masood
Published: December 2022

IntroductionSevere Acute Respiratory Syndrome Coronavirus-2 (SARS CoV 2) Covid-19 is responsible for the pandemic affecting the world population since 2019. Starting from Wuhan, China enveloped the globe within a few months. It affected the healthy population, but played havoc in terms of mortality and morbidity for old and diseased populations. Diabetes is a known condition putting patients at high risk of complications, resulting from metabolic syndrome-derived impaired immune responses. The world is still grappling with the challenge of managing diabetic patients with covid pneumonia and newly added Diabetics resulting from post covid complications driven by Covid-19-induced damage to pancreatic beta cells. Resulting in worsening of existing Diabetic control and new onset Diabetes (NOD) in susceptible individuals. The TYG (Triglyceride-Glucose Index) may serve as a marker to identify patients at risk of developing a serious illnessHypothesisTriglyceride Glucose Index is a marker for severity of Covid-19 and new onset of diabetes.Aim        To evaluate role of TYG index in prediction of new onset of Diabetes mellitus in Covid-19 patients and as a marker for disease severity in diabetic Covid-19 patients.MethodologyThis cross-sectional study was carried out in Combined Military Hospital (CMH) Rawalakot. Covid-19 patients' diagnosis was confirmed by RT-PCR. Glycosylated hemoglobin (HBA1c), fasting glucose and Triglycerides (TG) were performed at the biochemistry lab using SELECTRA chemical analyzer. TYG index was calculated and related with clinical symptoms of patients.ResultsA total of 2974 samples has been tested by RT-PCR. Three hundred and ninety-three (13%) were positive for COVID-19 infection. Twenty-one patients (5%) developed new-onset Diabetes (NOD) during the COVID infection. A TYG index of 43 people affected with COVID-19 (21 NOD and 22 non-diabetic individuals (control group) was calculated as a marker of severity index. It was found that the higher TYG was associated with severity and mortality in patients with COVID-19 diabetes.                         ConclusionCovid-19 infection is associated with worsening disease in preexisting diabetic patients and is responsible for new-onset Diabetes in patients. TYG index correlates directly with the severity of Covid-19. TYG index can be used as a predictor marker for mortality and morbidity in Covid-19.
Canibacter zhuwentaonis sp. nov. and Canibacter zhoujuaniae sp. nov., isolated from Marmota himalayana
Authors: Lv Xianglian , Li Yinmei , Cheng Yanpeng , Lai Xin-He , Yang Jing , Lu Shan , Zhang Gui , Yang Caixin , Jin Dong , Liu Liyun , Xu Jianguo
Published: December 2022

Four Gram-stain-positive, facultatively anaerobic, non-motile, non-spore-forming and rod-shaped bacteria (lx-72T, lx-45, ZJ784T and ZJ955) were isolated from the respiratory tract or faeces of marmot (Marmota himalayana) from the Qinghai–Tibet Plateau in China. Analysis of the 16S rRNA gene sequences showed that all strains belong to the genus

Canibacter

and are more related to

Canibacter oris

CCUG 64069T (95.1–97.4 % similarity) than to the genus

Leucobacter

. Both strain pairs grew well at pH 6–9 and 15–42°C, and ZJ784T/ZJ955 could tolerate slightly higher NaCl (0.5–4.5 %, w/v) than lx-72T/lx-45(0.5–3.5 %). Based on whole-genome sequences, the average nucleotide identity and digital DNA–DNA hybridization values between our four isolates and their closest relative were below the species delineation thresholds of 70 % and 95–96 %. The common major fatty acids (>10 %) of our four strains were anteiso-C15 : 0 and anteiso-C17 : 0. For both new type strains, MK-8(H4) and MK-9(H4) were the major isoprenoid quinones, and diphosphatidylglycerol and phosphatidylglycerol were the main polar lipids. The genomic DNA G+C content of all strains was 53.9 mol%. Based on results from the genomic comparison, phylogenetic analysis, and physiological and biochemical characteristics, the four isolates represent two novel species in the genus

Canibacter

, for which the names Canibacter zhuwentaonis sp. nov. (type strain lx-72T=KCTC 49658T=GDMCC 1.2569T) and Canibacter zhoujuaniae sp. nov. (type strain ZJ784T=KCTC 49507T=GDMCC 1.1997T) are proposed.
Streptomyces humicola sp. nov., a novel actinobacterium isolated from peat swamp forest soil in Thailand
Authors: Klaysubun Chollachai , Srisuk Nantana , Duangmal Kannika
Published: December 2022

A polyphasic approach was used to describe strain RB6PN25T, an actinobacterium isolated from peat swamp forest soil in Rayong Province, Thailand. The strain was a Gram-stain-positive and filamentous bacterium that contained
ll
-diaminopimelic acid, mannose and ribose in whole-cell hydrolysates. MK-9(H8) was the major menaquinone. The major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and iso-C15 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two unidentified glycophospholipids, two unidentified aminolipids and an unidentified phospholipid. The 16S rRNA gene sequences analysis indicated that it was most closely related to

Streptomyces rubrisoli

DSM 42083T (97.6 %) and

Streptomyces palmae

TBRC 1999T (97.4 %). Strain RB6PN25T exhibited low average nucleotide identity and digital DNA–DNA hybridization values with

S. rubrisoli

DSM 42083T (78.6 %, 23.2 %) and

S. palmae

TBRC 1999T (76.0 %, 22.6 %). The DNA G+C content of strain RB6PN25T was 69.9%. The results of phenotypic, chemotaxonomic, genotypic and phylogenetic analyses reveal that strain RB6PN25T represents a novel species of the genus

Streptomyces

, for which the name Streptomyces humicola sp. nov. is proposed. The type strain is RB6PN25T (=TBRC 14819T=NBRC 115204T).
Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity
Authors: Marciante Alexandria B. , Seven Yasin B. , Kelly Mia N. , Perim Raphael R. , Mitchell Gordon S.
Published: December 2022

Plasticity is a fundamental property of the neuromotor system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic nerve activity after exposure to intermittent low oxygen or acute intermittent hypoxia (AIH). pLTF can arise from distinct intracellular signaling cascades initiated by serotonin and adenosine; these cascades interact via powerful crosstalk inhibition. We demonstrate the serotonin/adenosine balance varies dramatically with time-of-day and details of the AIH protocol. Using a “standard” AIH protocol, the mechanism driving pLTF shifts from serotonin-dominant, adenosine-constrained during rest, to adenosine-dominant, serotonin-constrained in the active phase. This mechanistic ‘flip’ results from daily changes in basal spinal adenosine levels across time-of-day combined with hypoxia-evoked spinal adenosine release. Since AIH is emerging as a promising therapeutic modality to restore respiratory (and non-respiratory) movements in people with spinal injury or ALS, new knowledge that time-of-day and protocol details impact mechanisms driving pLTF has experimental, biological and translational implications.
Mechanical regulation of retinal vascular inflammation and degeneration in diabetic retinopathy
Authors: Chandrakumar Sathishkumar , Tierno Irene Santiago , Agarwal Mahesh , Lessieur Emma M. , Du Yunpeng , Tang Jie , Kiser Jianying , Yang Xiao , Kern Timothy S. , Ghosh Kaustabh
Published: December 2022

Vascular inflammation is known to cause degeneration of retinal vessels in early diabetic retinopathy (DR). Past studies investigating these diabetes-induced vascular abnormalities have focused primarily on the role of molecular or biochemical cues. Here we show that retinal vascular inflammation and degeneration in DR are also mechanically regulated by retinal vascular stiffening that is caused by overexpression of collagen-crosslinking enzyme lysyl oxidase (LOX) in retinal vessels. Treatment of diabetic mice with LOX inhibitor BAPN prevented the increase in retinal vascular stiffness, vascular ICAM-1 overexpression, and leukostasis. Consistent with these anti-inflammatory effects, BAPN treatment of diabetic mice blocked the upregulation of proapoptotic caspase-3 in retinal vessels, which concomitantly reduced retinal vascular degeneration and the diabetes-induced loss of contrast sensitivity in these mice. Finally, we show that increasing substrate stiffness alone increases the adhesiveness and neutrophil elastase-induced death of cultured retinal endothelial cells. By uncovering a link between LOX-dependent vascular stiffening and the development of retinal vascular and functional defects in diabetes, these findings offer unique insights into DR pathogenesis that has important translational potential.
A multi-method study to identify and validate alcohol diagnostics for injury-related trauma in South Africa: a study protocol
Authors: Williams Petal Petersen , Prinsloo Megan R. , Peden Margaret M. , Neethling Ian , Mhlongo Shibe , Maqungo Sithombo , Parry Charles , Matzopoulos Richard
Published: December 2022

Introduction

The burden of alcohol use among trauma patients and the relative injury risks is not routinely measured in South Africa (SA). Given the prominent burden of alcohol on hospital trauma departments, SA needs practical, cost-effective and accurate alcohol diagnostic tools for testing, surveillance and clinical management of trauma patients. This study aims to validate alcohol diagnostics for injury-related trauma and assess its utility for improving national health practice and policy.

Methods and Analysis

The Alcohol Diagnostic Validation for Injury-Related Trauma (AVIRT) study will use mixed methods across three work packages. Focus Group Discussions will be conducted with key stakeholders across four areas of expertise (clinical, academic, policy and operational) to determine the type of alcohol information that will be useful for different stakeholders in the injury prevention and healthcare sectors. We will then conduct a validation study of alcohol diagnostic tools (clinical assessment, breath analysis, finger-prick blood) against enzyme immunoassay blood concentration analysis in a tertiary hospital trauma setting. Finally, selected alcohol diagnostic tools will be tested in a district hospital setting alongside community-based participatory research on the utility of the selected tools.

Ethics and dissemination

The study was approved by the Research Ethics Committee of the South African Medical Research Council and the Western Cape Health Department. Findings will be disseminated to inform strategies to introduce routine, cost-effective alcohol diagnostics optimally in a high trauma setting by ensuring accuracy, real world feasibility and institutional support.

Strengths and limitations of this study

The study will provide an understanding of the impact of alcohol and its association with injuries, highlight the burden alcohol-related injuries impose on health workers, inform policies to mitigate alcohol harm, and recommend methods to scale-up alcohol screening and detection in trauma patients nationally.

The study setting will complement the limited evidence base on alcohol consumption in LMICs.

Expert stakeholders included in focus group discussions will be restricted to known contacts within the field.

Validity testing of the alcohol diagnostics will use enzyme immune assay instead of the gold standard gas chromatography method, which was too expensive.

Results will be generalisable to patients treated at public-sector district and tertiary-level facilities, that treat a higher proportion of moderate to severe injuries.
A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a non-hemophiliac state
Authors: Teranishi-Ikawa Yuri , Soeda Tetsuhiro , Koga Hikaru , Yamaguchi Kazuki , Kato Kazuki , Esaki Keiko , Asanuma Kentaro , Funaki Miho , Ichiki Mina , Ikuta Yuri , Ito Shunsuke , Joyashiki Eri , Komatsu Shun-Ichiro , Muto Atsushi , Nishimura Kei , Okuda Momoko , Sanada Hisakazu , Sato Motohiko , Shibahara Norihito , Wakabayashi Tetsuya , Yamaguchi Koji , Matsusaki Akiko , Sampei Zenjiro , Shiraiwa Hirotake , Konishi Hiroko , Kawabe Yoshiki , Hattori Kunihiro , Kitazawa Takehisa , Igawa Tomoyuki
Published: December 2022

Emicizumab, a factor (F)VIIIa-function mimetic bispecific antibody (BsAb) to FIXa and FX, has become an indispensable treatment for people with hemophilia A (PwHA). Although emicizumab is very potent, long-term outcomes from the clinical studies suggest that a small proportion of PwHA still experiences bleeds. Additionally, non-clinical studies indicate that the maximum cofactor activity of emicizumab is lower than international standard activity (100 IU/dL of FVIII). An increased cofactor activity BsAb would benefit such patients. Here, we report NXT007, a BsAb binding FIXa and FX developed through further engineering of emicizumab. Emicizumab has a common light chain, but through advances in antibody engineering, we were able to create a more potent BsAb with two new non-common light chains. After extensive optimization of the heavy and light chains, the resulting BsAb, NXT007, exerted in vitro thrombin generation (TG) activity in hemophilia A plasma equivalent to 100 IU/dL of FVIII when triggered by tissue factor. NXT007 demonstrated potent hemostatic activity in an acquired hemophilia A model in non-human primates at a much lower dosage than emicizumab, consistent with an around 30-fold dose shift in the in vitro TG activity between NXT007 and emicizumab. Moreover, together with Fc engineering that enhanced FcRn binding and reduced in vivo clearance, we demonstrate that NXT007 could be effective at a much lower dosage with a longer dosing interval compared to emicizumab. These non-clinical results suggest that NXT007 could maintain a non-hemophilic range of coagulation potential in PwHA and provides a rationale for its clinical testing.
Inverse identification of region-specific hyperelastic material parameters for human brain tissue
Authors: Hinrichsen Jan , Reiter Nina , Bräuer Lars , Paulsen Friedrich , Kaessmair Stefan , Budday Silvia
Published: December 2022

The identification of material parameters accurately describing the region-dependent mechanical behavior of human brain tissue is crucial for computational models used to assist, e.g., the development of safety equipment like helmets or the planning and execution of brain surgery. While the division of the human brain into different anatomical regions is well established, knowledge about regions with distinct mechanical properties remains limited. Here, we establish an inverse parameter identification scheme using a hyperelastic Ogden model and experimental data from multi-modal testing of tissue from 19 anatomical human brain regions to identify mechanically distinct regions and provide the corresponding material parameters. We assign the 19 anatomical regions to nine governing regions based on similar parameters and microstructures. Statistical analyses confirm differences between the regions and indicate that at least the corpus callosum and the corona radiata should be assigned different material parameters in computational models of the human brain. We provide a total of four parameter sets based on the two initial Poisson’s ratios of 0.45 and 0.49 as well as the pre- and unconditioned experimental responses, respectively. Our results highlight the close interrelation between the Poisson’s ratio and the remaining model parameters.

The identified parameters will contribute to more precise computational models enabling spatially resolved predictions of the stress and strain states in human brains under complex mechanical loading conditions.
LRRK2 Kinase Activity Regulates Parkinson’s Disease-Relevant Lipids at the Lysosome
Authors: Maloney Michael T. , Wang Xiang , Ghosh Rajarshi , Andrews Shan V. , Maciuca Romeo , Masoud Shababa T. , Caprioli Richard M. , Chen John , Chiu Chi-Lu , Davis Sonnet S. , Ho Audrey Cheuk-Nga , Nguyen Hoang N. , Propson Nicholas E. , Reyzer Michelle L. , Davis Oliver B. , Deen Matthew C. , Zhu Sha , Di Paolo Gilbert , Vocadlo David J. , Estrada Anthony A. , de Vicente Javier , Lewcock Joseph W. , Arguello Annie , Suh Jung H. , Huntwork-Rodriguez Sarah , Henry Anastasia G.
Published: December 2022

Lysosomal dysfunction is a hallmark of Parkinson’s disease (PD), and variants in several PD-associated genes, includingLRRK2, perturb lysosomal homeostasis. Based on this, LRRK2 kinase inhibition is being explored as a therapeutic approach for the treatment of PD. LRRK2 inhibitors reduce levels of BMP, an endolysosomal lipid involved in glycosphingolipid (GSL) catabolism, in urine from preclinical models and clinical subjects, however, the mechanisms by which LRRK2 regulates BMP and the functional significance of this change to disease are undefined. We establish that LRRK2 regulates secretion of BMP- and GSL-containing vesicles from kidney into urine and modulates BMP and GSL levels in the brain. BMP accumulates within lysosomes as a secondary response to LRRK2’s effects on the activity of glucocerebrosidase (GCase), a PD-linked enzyme involved in GSL catabolism. Alterations in BMP and GCase substrate turnover are observed in CSF from LRRK2-PD patients, highlighting the relevance of LRRK2-dependent lysosomal dysfunction in disease.
Silencing neuroinflammatory reactive astrocyte activating factors ameliorates disease outcomes in perinatal white matter injury
Authors: Renz Patricia , Surbek Daniel , Haesler Valérie , Tscherrig Vera , Huang Eric J , Chavali Manideep , Liddelow Shane , Rowitch David , Schoeberlein Andreina , Lutz Amanda Brosius
Published: December 2022

The role of reactive astrocytes in perinatal white matter injury (WMI) is unclear. In a mouse model of WMI, we provide evidence that impairing the formation of aC3-expressing neuroinflammatory reactive astrocyte sub-state rescues myelination and behavioral deficits. We further demonstrate the presence ofC3-expressing reactive astrocytes in human WMI. Our data point to these cells as putative drivers of myelination failure in WMI and a potentially promising therapeutic target.
Investigating forms of graduate capital and their relationship to perceived employability: an application of PLS predict and IPMA
Authors: Agnihotri Shikha , Shiva Atul , Khan Farha Naz
Published: December 2022

Purpose

The study aims to assess the relationship between cultural capital, human capital, psychological capital, social capital and perceived employability of management graduates.

Design/methodology/approach

The data was analysed through variance based partial least square (PLS) structural equation modelling on 505 management students by an online questionnaire. The predictive relevance of perceived employability was investigated with PLS predict approach. Further, importance-performance map analysis (IPMA) was applied to assess important and performing dimensions of perceived employability.

Findings

The results indicate that social capital was found to be the strongest predictor of graduates' perceived employability. The proposed conceptual model was found to have a moderate to high predictive relevance. IPMA results suggested that investment in psychological capital leads to higher return in perceived employability of management graduates.

Research limitations/implications

Data was collected using purposive sampling and confined to university students only.

Practical implications

Findings of the study provide empirical inferences in support of human capital, social capital and social cognitive theory. Practical implications offer important inputs to policy makers, higher educational institutes, career counsellors and universities.

Originality/value

This study provides novel inputs by a comprehensive model of graduate capital to determine and predict perceived employability of graduates in emerging economy like India.
Computational study of dynamics of confined droplets under electric field: effect of contact angle
Authors: Cao Qianqian , Li Lujuan , You Hao , Liu Hao
Published: December 2022

Purpose

The contact behaviors of droplets on confined surfaces influence significantly their dynamics and morphological transition induced by the electric field. This paper aims to delve into the electric stress, electric field distribution, flow field and evolution of droplet neck to understand the underlying mechanisms.

Design/methodology/approach

Electrohydrodynamics of droplets in confined environment is numerically analyzed based on finite volume method (FVM) combining with volume-of-fluid (VOF) method for two-phase interface capturing. Numerical solutions are obtained through solving electrohydrodynamics model coupling fluid dynamics with electrostatics.

Findings

It was found that the droplet neck with high interfacial curvature undergoes different transition depending on the contact angle. At large domain height, the droplets on the surfaces with the contact angle of θ < 90° tend to break up into smaller droplets adhered on top and bottom surfaces. The detachment of droplets is identified when the contact angle is much greater than 90°. Notably, the droplets at θ = 90° exhibit asymmetrical shape evolution, but for other cases there is symmetrical shape of droplets during transition process. With decreasing the domain height, no obvious deformation through driving the contraction of the droplet neck is observed.

Originality/value

It remains unclear how the electric field parallel to the surfaces affects the shape transition and electrohydrodynamics of confined droplets when changing the contact angle. In this paper, the authors study the electrohydrodynamics of droplets in confined space when the electric field is exerted parallel to contact surfaces. In particular, the authors consider the effect of the surface wettability on the droplet deformation. The problem is solved through FVM combining with the VOF method to implement the capturing of two-phase interfaces. The results indicate that the electrohydrodynamic behaviors of droplets are sensitive to the contact properties of droplets on the surfaces, which has not been reported in previous works.
Toward the development of an Islamic banking sustainability performance index
Authors: Ammar Rym , Rebai Sonia , Saidane Dhafer
Published: December 2022

Purpose

The purpose of this paper is to suggest a model that yields a sustainability performance index for Islamic banks (IBs). This index is expected to account for stakeholders’ viewpoints while considering sustainability and Maqasid Al-Shariah as bases.

Design/methodology/approach

First, based on the relevant literature review refined through consultations with academic, banking and Shariah experts, the main stakeholders and their corresponding lists of relevant attributes and sub-attributes are identified. Then, adopting a multi-attribute utility approach and based on a second step of interviews with experts, an aggregated index is suggested. Finally, the developed index is applied to five famous Islamic banking groups over the period 2005–2019.

Findings

Empirical evidence shows that the banks used in the implementation do not achieve high scores of the suggested index. This can be interpreted through a lack of Islamic normative aspects and low adherence to sustainability practices. Specifically, they are not functioning on a justice basis and are deficient in providing sufficient varieties of Islamic products. They are also more interested in economic sustainability and are not involved in environmental and social ones.

Originality/value

The developed index not only considers the compliance of the banking activities with Shariah, but it also addresses their sustainability from the main stakeholders’ perspectives. The suggested model provides a transparent performance evaluation tool for IBs omitting all causes of conflict of interests and certifies the fairness of the resulting assessments.
Event-triggered aperiodic intermittent sliding-mode control for master–slave bilateral teleoperation robotic systems
Authors: Gao Hang , Ma Chao
Published: December 2022

Purpose

The purpose of this paper is to propose a novel event-triggered aperiodic intermittent sliding-mode control (ETAI-SMC) algorithm for master–slave bilateral teleoperation robotic systems to further save communication resources while maintaining synchronization precision.

Design/methodology/approach

By using the Lyapunov theory, a new event-triggered aperiodic intermittent sliding-mode controller is designed to synchronize master–slave robots in a discontinuous method. Unlike traditional periodic time-triggered continuous control strategy, a new ETAI condition is discussed for less communication pressure. Then, the exponential reaching law is adopted to accelerate sliding-mode variables convergence, which has a significant effect on synchronization performance. In addition, the authors use quantizers to make their algorithm have obvious progress in saving communication resources.

Findings

The proposed control algorithm performance is validated by an experiment developed on a practical bilateral teleoperation system with two PHANToM Omni robotic devices. As a result, the synchronization error is limited within a small range and the control frequency is evidently reduced. Compared with a conventional control algorithm, the experimental results illustrate that the proposed control algorithm is more sensitive to system states changes and it can further save communication resources while guaranteeing the system synchronization accuracy, which is more practical for real bilateral teleoperation robotic systems.

Originality/value

A novel ETAI-SMC for bilateral teleoperation robotic systems is proposed to find a balance between reducing the control frequency and synchronization control precision. Combining the traditional sliding-mode control algorithm with the periodic intermittent control strategy and the event-triggered control strategy has produced obvious effect on our control performance. The proposed ETAI-SMC algorithm helps the controller be more sensitive to system states changes, which makes it possible to achieve precise control with lower control frequency. Moreover, we design an environment contact force feedback algorithm for operators to improve the perception of the slave robot working environment. In addition, quantizers and the exponential convergence law are adopted to help the proposed algorithm perform better in saving communication resources and improving synchronization precision.
Can Alexa serve customers better? AI-driven voice assistant service interactions
Authors: Malodia Suresh , Ferraris Alberto , Sakashita Mototaka , Dhir Amandeep , Gavurova Beata
Published: December 2022

Purpose

This study aims to examine customers’ willingness to engage in service interactions enabled by artificial intelligence (AI) controlled voice assistants (VA). Drawing on the tenets of dual-factor theory, this study measures the impact of both enablers and inhibitors – mediated by trust in Alexa – on customers’ intentions to transact through VAs.

Design/methodology/approach

Data from a survey of 290 users of VAs from Japan was collected through “Macromill”. The authors used a covariance-based path analysis technique for data analysis after establishing the validity and reliability of the measures.

Findings

The results of this study demonstrate that convenience and status-seeking act as enablers and positively influence trust in VAs, whereas risk barrier acts as an inhibitor and negatively influence trust in VAs. In turn, trust in VAs positively influences the intention to use VAs for transactional service interactions. This association is positively moderated by technology comfort.

Originality/value

This study applies dual-factor theory to the context of VAs – a context that scholars have, to date, examined solely from a technology adoption perspective. For the first time, the authors adopt a dual-factor approach to identify a new set of antecedents for customers’ intentions to use VAs for transactional service interactions.
Audit partner characteristics, career advancement and audit quality in the USA
Authors: Cai Chen , Ciccone Stephen , Li Huimin , Xu Le Emily
Published: December 2022

Purpose

This study aims to explore the relation among US audit partners’ characteristics, their career advancement and audit quality.

Design/methodology/approach

This study uses data from Public Company Accounting Oversight Board Form AP, Auditor Reporting of Certain Audit Participants, and publicly available online data sources. The hand-collected data on audit partners’ personal characteristics include gender, work experience and educational background. The measures for audit quality include restatements and audit fees.

Findings

The authors find that audit partner characteristics matter for the time it takes an individual to reach partnership after completing a bachelor’s degree. There are significant differences in work experience and educational background between partners in the largest (Big N) audit firms and smaller (non-Big N) audit firms. Audit partner traits are related to audit quality, and the effects differ between Big N and non-Big N partners.

Originality/value

The literature has examined audit partners’ career paths using international data. However, little empirical academic research has examined the career advancement of US audit partners. This study provides initial insights on the career advancement of US partners on a large scale and complements the recent research that examines audit partner characteristics and audit quality in the US market.
Financial inclusion: philosophical and methodological underpinnings
Authors: Sapre Nikhil
Published: December 2022

Purpose

Financial inclusion is broadly described as the ability of individuals and businesses to access useful and affordable financial products and services that meet their needs – transactions, payments, savings, credit and insurance – delivered in a responsible and sustainable way. It is considered a key driver of economic growth and financial well-being. Given the significance and relevance of this topic, the purpose of this note is to critically evaluate the ontological and epistemological stance of existing research on financial inclusion. Furthermore, this note examines the influence on the research design.

Design/methodology/approach

Beginning with a brief description of the key concepts, this note presents a conceptual framework and substantiates the recommended philosophical paradigm through a detailed appraisal of its appropriateness, relative strengths and limitations.

Findings

Drawing from a range of philosophical worldviews, which can at times seem indistinguishable especially in finance and economics, this note proposes that objectivism with a realist approach is foundational to academic research on financial inclusion. Furthermore, this note makes recommendations with regards to research design.

Originality/value

This note not only presents a comprehensive assessment of the problematics and the underlying metatheoretical assumptions proposed by Cunliffe (2011) but is also, to the best of author’s knowledge, the first to highlight its relevance to the formal financial system in general and to financial inclusion in particular.
An investigation into the potential of water retted fiber from agricultural waste of Curcuma longa plant for textile application
Authors: Martina Tina , Wardiningsih Wiah , Rianti Ajeng , Rudy Ryan , Pradana Samuel Martin
Published: December 2022

Purpose

The purpose of this study was to characterize the fiber from Curcuma longa (turmeric) stems. The fiber’s properties were used to assess its potential for textile yarn production.

Design/methodology/approach

The natural fiber used in this investigation was extracted from agricultural waste through a cold water-retting process.

Findings

The Curcuma longa fiber had a crystallinity of 50%. Cellulose, hemicellulose and lignin were detected in the fibers’ Fourier transform infrared spectra. A Curcuma longa fiber bundle contains several constituent fibers. The fibers exhibited an irregular cross-section, with a variable oval shape for the lumen. The fibers of Curcuma longa averaged 30.22 cm in length. The fineness of the fibers was 6.58 Tex. In this study, Curcuma longa fibers had an 11.30% moisture regain. The tensile strength of the fibers was 19.18 g/Tex. Curcuma longa fibers showed a break elongation of 9.79%. The fiber coefficient of friction was 0.3.

Originality/value

Curcuma longa has characteristics that make it appropriate for industrial uses like spinning. Thus, it is possible to use Curcuma longa fiber as a raw material for textiles.