bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior instrumentation for osteoporotic fractures in the thoracic or lumbar spine: Cement-augmented pedicle screws vs hybrid constructs
Authors: Chou Po-Hsin , Lin Hsi-Hsien , Yao Yu-Cheng , Wang Shih-Tien , Chang Ming-Chau , Liu Chien-Lin
Published: January 2023

Background:

Cement-augmented pedicle screws (CPS) and hybrid construct (HC), consisting of pedicle screws and additional hooks, are common fixation methods for osteoporotic spine fracture. No study has compared surgical results of CPS and HC for treating osteoporotic spine fracture. The aim of the study was to compare surgical results using CPS or HC for osteoporotic fractures of the thoracic or lumbar spine.

Methods:

This retrospective cohort study included 84 patients who received surgical treatment with CPS (n = 43) or HC (n = 41) for osteoporotic spine fractures from January 2011 to December 2015, with a mean follow-up of 67 months. Sixty-five patients with neurological deficits received long posterior instrumentation, short posterior decompression, and posterolateral fusion. The 19 patients without neurologic deficits received long posterior instrumentation without posterior decompression and fusion. Radiographic, clinical, and neurologic outcomes were evaluated.

Results:

The HC group had significantly shorter operative times (231 vs 258 minutes), greater blood loss (497 vs 427 mL), better immediate postoperative kyphosis reduction (10.6° vs 9.1°), and greater final reduction loss (9.8° vs 7.1°) than the CPS group. In both groups, significant loss of the kyphotic angle was apparent during follow-up. Improved ambulation after surgery occurred in 51.2% and 58.5% of patients in the CPS and HC groups, respectively. Neurologic function after surgery improved 0.5 and 0.7 grades in the CPS and HC groups, respectively. Implants failed in 2.3% and 2.4% of patients in the CPS and HC groups, respectively. The incidence of cement leakage from screw augmentation was 38.9%.

Conclusion:

The CPS and HC techniques for treating osteoporotic fractures of the thoracic or lumbar spine did not differ statistically in terms of improved radiologic and clinical outcomes, final neurologic and ambulatory function, or implant failure rates, making them equally comparable alternatives.
Using Trident distal radial locking plate to fix the fracture of distal radius volar rim
Authors: Huang Yin-Ming , Chen Chun-Yu , Lin Kai-Cheng , Lai Wei-Yi , Lin Yi-Ying , Fu Yun-Ju , Tarng Yih-Wen
Published: January 2023

Background:

The volar locking plates have been widely used in a variety of distal radius fractures, but they still have several limitations when dealing with small fragments located around the watershed line with widely reported complications. The volar rim fragments play a critical role in radiocarpal joint stability and failing to secure the volar rim fragment usually results in carpal instability, subluxation, or even dislocation. This study investigates clinical outcomes in the use of a novel implant, the Trident distal radial (TDR) locking plate to treat distal radius fracture with the intermedium column edge (lunate fossa volar rim) fragment involvement.

Methods:

A retrospective study of 25 patients was conducted, all patients had intermedium column fractures with lunate fossa volar rim involvement and treat with the TDR between January 2016 and December 2019. The clinical assessment outcomes included VAS Pain, PRWE, and DASH scores. Objective measurements included ROM of the injured wrist and grip strength. Final radiographs were used to evaluate radial inclination, volar tilt, ulnar variance, and distal radioulnar joint instability. Secondary operations related to hardware complications were also recorded.

Results:

The outcome revealed that the mean VAS Pain Score was 1.3, mean DASH score was 10.5, and mean PRWE score was 9.3. Objective measurements revealed good ROM recovery and an 89% gripping strength recovery compared with contralateral hand. Radiographic measurements revealed good maintenance of volar tilt, radial inclination, and mean ulnar variance. There were no complications related to the implant and all fracture sites were union.

Conclusion:

We believe that the TDR provided more stable fixation among distal radial fractures that predominantly involved the intermedial column and volar rim fragment, and allowing early rehabilitation. We could obtain excellent results in the wrist ROM, gripping power, and Pain Score (VAS).
Estimating Effects of Wages on Smoking Prevalence Using Labor Unions as Instrumental Variables
Authors: Leigh J. Paul , Chakalov Bozhidar T.
Published: January 2023

Objectives

To test for the effects of wages on smoking using labor unions as instrumental variables.

Methods

We analyzed four waves of the Panel Study of Income Dynamics (2013 to 2019 alternate years). The overall sample included workers aged 18 to 70 years in 2013 and subsamples within blue + clerical/white-collar and private/public sector jobs (N = 37,117 to 8446 person-years). We used two instrumental variables: worker's union membership and states' right-to-work laws.

Results

$1 (2019 US dollars) increases in wages-per-hour resulted in 1.3 (P < 0.001) percentage point decreases in smoking prevalence (8.2% decreases at the smoking mean). Larger effect sizes and strong statistical significance were found for blue-collar + clerical and private-sector subsamples; smaller sizes and insignificance were found for public-sector and white-collar subsamples.

Conclusions

Unions increase wages, and higher wages, in turn, reduce smoking. Wages and labor unions are underappreciated social determinants of health.
Pediatric Critical Care–Associated Parental Traumatic Stress: Beyond the First Year*
Authors: Whyte-Nesfield Mekela , Kaplan Daniel , Eldridge Peter S. , Gai Jiaxiang , Cuddy William , Breeden Karli , Ansari Nadia , Siller Pamela , Mennella Jenna M. , Nkromah Toah A. , Youtz Meghan , Thomas Neal , Li Simon
Published: January 2023

OBJECTIVES:

Perform a longitudinal analysis of parental traumatic stress up to 30 months after PICU discharge.

DESIGN:

Prospective observational cohort study.

SETTING:

Two tertiary care children’s hospitals with mixed medical/surgical/cardiac PICUs.

SUBJECTS:

Parents of patients unexpectedly admitted to the PICU.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Two hundred sixty-five parents of 188 children were enrolled. Of the 195 parents who completed the 3–9-month assessments, 29 (14.8%) met posttraumatic stress disorder (PTSD) qualification on the PTSD Symptom Scale Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Multivariable analysis showed parents who met acute stress disorder (ASD) qualification (odds ratio [OR] 8.01; 95% CI 2.64–24.3), parents of children with Pediatric Overall Performance Category score of severe or coma at discharge (OR 5.21; 95% CI 1.65–16.4), parents who had concerns for their child’s permanent injury (OR 1.82; 95% CI 1.36–2.43), and parents who reported increased knowledge of child illness during admission (OR 1.82; 95% CI 1.13–2.93) had increased odds of developing parental PTSD. Of the 175 parents (66%) who completed the 18–30-month assessments, 22 (12.5%) met PTSD qualification. Multivariable analysis showed parents who met ASD qualification (OR 4.19; 95% CI 1.12–15.7), parents who had a history of a family member or themselves being admitted to ICU (OR 6.51; 95% CI 1.43–29.6), and parents who had concerns of child’s susceptibility to death post discharge (OR 1.58; 95% CI 1.19–2.09) had increased odds of developing parental PTSD. At 18–30 months post discharge, parents who met the PTSD qualification were more likely to report a decrease in household income following discharge (OR 9.23; 95% CI 1.71–49.9).

CONCLUSIONS:

Parental PTSD remains a significant morbidity of PICU admission for a subgroup of parents greater than 18 months post admission. Identifiable risk factors will inform the development of targeted interventions.
Monitoring in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Bhalla Anoopindar , Baudin Florent , Takeuchi Muneyuki , Cruces Pablo ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

Monitoring is essential to assess changes in the lung condition, to identify heart-lung interactions, and to personalize and improve respiratory support and adjuvant therapies in pediatric acute respiratory distress syndrome (PARDS). The objective of this article is to report the rationale of the revised recommendations/statements on monitoring from the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2).

DATA SOURCES:

MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:

We included studies focused on respiratory or cardiovascular monitoring of children less than 18 years old with a diagnosis of PARDS. We excluded studies focused on neonates.

DATA EXTRACTION:

Title/abstract review, full-text review, and data extraction using a standardized data collection form.

DATA SYNTHESIS:

The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. We identified 342 studies for full-text review. Seventeen good practice statements were generated related to respiratory and cardiovascular monitoring. Four research statements were generated related to respiratory mechanics and imaging monitoring, hemodynamics monitoring, and extubation readiness monitoring.

CONCLUSIONS:

PALICC-2 monitoring good practice and research statements were developed to improve the care of patients with PARDS and were based on new knowledge generated in recent years in patients with PARDS, specifically in topics of general monitoring, respiratory system mechanics, gas exchange, weaning considerations, lung imaging, and hemodynamic monitoring.
Craniocervical Instability in Oculoauriculovertebral Spectrum
Authors: Gomes Luiz Paulo , Ferraz Beatriz Gonçalves , Brandão Michele Madeira , Alonso Nivaldo , Pittoli Siulan Vendramini , Tonello Cristiano
Published: January 2023

Introduction:

The oculoauriculovertebral spectrum (OAVS) are anomalies of the first and second pharyngeal arches, causing craniofacial changes, principally facial asymmetry, as well as anomalies in the spine, that can be a cause of instability of the craniocervical junction - manipulation of an unstable spine can result in morbimortality. However, few studies have related OAVS to craniocervical instability.

Objectives:

Correlate patients with OAVS through radiography with craniocervical instability and prediction of its occurrence.

Material and Methods:

Through a radiographic study of the cervical spine, the assessment of vertebral malformations and the presence of craniocervical instability was performed and clinical assessment using the OMENS score as a phenotypic criteria for patients with OAVS, by a specialized multidisciplinary team. Student’s t test, Kolmogorov-Smirnova, and χ2 were performed.

Results:

Twenty-six patients with OAVS were evaluated, 7 (26.9%) had craniocervical instability, the OMENS score was 3 times higher, but without statistical significance. All patients with instability also had spinal malformations, and of those without craniocervical instability (19 patients), 57.8% had spinal malformations. Vertebral malformations had a similar incidence in those with and without instability, the most common being scoliosis. There was no statistical significance in the presence or absence of spinal malformations with the presence or absence of craniocervical instability. Extracraniofacial findings were found in all patients with instability; 71.4% of them were radial.

Conclusions:

Patients with higher OMENS scores had more craniocervical instability but without statistical significance. It also did not show statistical relevance between the presence of malformations and craniocervical instability.
Home Safety, Quality of Life, Fall, and Fear of Falling Among Older Home Care Recipients
Authors: Cakir Nurcan Pirgan , Mandiracioglu Aliye , Hassoy Hur , Horasan Gonul Dinc
Published: January 2023

Background and Purpose:

Fear of falling is the worry that appears with the fall, and it is quite commonly seen in older adults. The aim of the study was to detect the fear of falling and related factors in older persons who are receiving home care services provided by Bornova Municipality.

Methods:

This cross-sectional study was conducted with the participation of 386 individuals older than 60 years. The data were collected via face-to-face interviews by a questionnaire form, May-October, 2018. The fear of falling was measured by The Falls of Efficacy Scale-International. In addition, a questionnaire to collect sociodemographic data, retrospective history of falls, Instrumental Activities of Daily Living, EuroQol-5D, and Home Security Control List was used.

Results:

The mean age of the sample was 77.66 ± 7.59 years and females constituted 74.6% of them. Of the participants, 74.1% were detected to have fear of falling. The logistic regression analysis showed a significant association between the fear of falling and fall history, quality of life, and health status visual analog scale scores.

Conclusion:

It can be argued that the fear of falling is higher in the individuals who have a past experience of falling and the individuals who have a low quality of life. The older adults who have falls history should be determined as a risk group and protective measures should be applied to enhance their life quality.
Physiotherapy, Local Acupuncture, and Auricular Acupuncture for Frozen Shoulder
Authors: Hollisaz Mohammad Taghi , Khatibi Aghda Amidoddin , Asheghan Mahsa , Amanollahi Asadollah , Hashemi Seyed Ebrahim
Published: January 2023

Purpose:

To compare local acupuncture and auricular acupuncture with physiotherapy in the treatment of frozen shoulder.

Methods:

A randomized clinical trial with 3 parallel groups in an outpatient clinic was conducted at a university hospital. In total, 116 participants with frozen shoulder were randomly allocated to 3 groups and underwent physiotherapy or local acupuncture or auricular acupuncture. Shoulder active and passive ranges of motion were assessed, and the Shoulder Pain and Disability Index questionnaire was used to assess pain and disability before and after the treatments.

Results:

Active and passive ranges of motion were best improved by physiotherapy in abduction and flexion (all P < .001). Passive external rotation was best increased after physiotherapy (P = .030). For active external and internal rotation, and also for passive internal rotation, there were no significant differences among the treatments. Pain reduction was more successful with acupuncture, especially with auricular acupuncture (P < .001). Auricular acupuncture was more effective in improving patients' functional abilities (P < .001). None of the participants reported any side effects resulting from the treatments.

Conclusion:

Acupuncture, particularly auricular acupuncture, is more effective in relieving pain and decreasing disability than physiotherapy. All the interventions were beneficial in improving range of motion.
Development of a Safe Mobilisation Program to Improve Functional Mobility and Reduce Fall Risk in Older Adults With Cognitive Impairment and Gait Disorders
Authors: Zhang Weihong , Low Lee-Fay , Gwynn Josephine Diana , Clemson Lindy
Published: January 2023

This article describes the development process of the Safe Mobilisation Program to improve functional mobility and reduce fall risk in cognitively impaired older adults with gait disorders. We drew on a systematic review, informed by a theoretical paper and data collected during a feasibility study. Data collected were field notes of observation and participant feedback. Reflexive thematic analysis was undertaken. Home-based, one-on-one, low-intensity interventions are suitable designs. Key features of the tailored intervention to enhance participation include collaborative goal setting, individualized activities, rapport building, and carer training. Strategies targeting gait and cognitive deficits are integral to achieving optimal outcomes.
Heart Failure and Frailty Have Synergistic Negative Effects on Skeletal Muscle Mass and Upper and Lower Limb Muscle Strength
Authors: Umehara Takuya , Kaneguchi Akinori , Yamasaki Takahiro , Matsuura Akihiro , Katayama Nobuhisa , Kawakami Wataru , Kuwahara Daisuke , Kito Nobuhiro , Kakehashi Masayuki
Published: January 2023

This study aimed to examine the interaction effect between the presence of heart failure and the degree of frailty on skeletal muscle mass index (SMI), handgrip strength, and 5 times sit-to-stand (5STS). This study revealed a significant interaction effect between the presence of heart failure and the degree of frailty on SMI, handgrip strength, and 5STS. The study results revealed that the combination of heart failure and frailty has synergistic negative effects on SMI and upper and lower limb muscle strength.
Preoperative Opioid and Benzodiazepine Use: Influence on Abdominal Surgical Outcomes
Authors: Fagenson Alexander M , Schleider Christine , Philp Matthew M , Noonan Kristin M , Braun Pamela A , Cowan Scott , Pitt Henry A ,   On behalf of the Pennsylvania NSQIP Consortium
Published: January 2023

Background:

Preoperative opioid use has been shown to be associated with worse outcomes after surgery. However, little is known about the effect of preoperative benzodiazepines (BDZs) with and without opioids. The aim of this study was to determine the influence of preoperative substance use on outcomes after abdominal surgery.

Study Design:

Patients undergoing abdominal operations including ventral hernia, colectomy, hysterectomy, cholecystectomy, appendectomy, nephrectomy and hiatal hernia were identified in an Opioid Surgical Steward program by a regional NSQIP consortium in 2019-2021. ACS-NSQIP data were linked with custom substance use variables created by the collaborative. Univariable and multivariable analyses were performed for 30-day outcomes.

Results:

Of 4,439 patients, 64% (N=2,847) were female with a median age of 56 years. The most common operations performed were hysterectomy (22%), ventral hernia repair (22%) and colectomy (21%). Preoperative opioid use was present in 11% of patients (N = 472); 10% (N = 449) were on BDZs, while 2.3% (N = 104) were on both. Serious morbidity was significantly (p < 0.001) increased in patients on preoperative opioids (16% vs. 7.9%) and BDZs (14% vs. 8.3%) compared to their naïve counterpart, and this effect was amplified in patients on both substances (20% vs. 7.5%). Multivariable regression analyses reveal that preoperative substance use is an independent risk factor (p < 0.01) for overall morbidity and serious morbidity.

Conclusions:

Preoperative opioid and benzodiazepine use are independent risk factors that contribute to postoperative morbidity. This influence on surgical outcomes is exacerbated when patients are on both substances.
Pseudomonas paralcaligenes sp. nov., isolated from a hospitalized patient
Authors: Ono Emi , Tohya Mari , Watanabe Shin , Tada Tatsuya , Kuwahara-Arai Kyoko , Oshiba Akihiro , Izumi Namiki , Kirikae Teruo
Published: January 2023

A Gram-stain-negative, aerobic, rod-shaped, non-endospore-forming bacterium, designated as strain MRCP1333T, was isolated from a faecal sample from a hospital patient in Japan. MRCP1333T grew at temperatures of 15–40 °C (optimum 25–35 °C), with 1.0–3.0 % (w/v, 171–513 mM) NaCl [optimum 1–2 % (w/v), 171–342 mM], and at pH 6.0–9.5 (optimum pH 7.0–8.0). The results of phylogenetic analysis based on the sequences of the 16S rRNA gene and the 53 genes encoding the bacterial ribosome protein subunits indicated that MRCP1333T represented a member of the

Pseudomonas aeruginosa

group, most closely related to

Pseudomonas alcaligenes

. Whole-genome comparisons, using average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity, confirmed that MRCP1333T represented a distinct species in the

P. aeruginosa

group. Phenotypic characterization tests demonstrated utilization by this strain of citrate, glycerol, and d-malic acid, the ability to reduce nitrite to nitrogen and the ability of this strain to grow in the presence of minocycline and tetrazolium blue, distinguishing this strain from

P. alcaligenes

and other closely related species of the

P. aeruginosa

group. The major fatty acids of MRCP1333T were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c; 38.4 %), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c; 21.1 %) and C16 : 0 (20.6 %). The DNA G+C content of MRCP1333T was 66.5 mol%. Genetic and phenotypic evidence indicated that MRCP1333T should be classified as representing a novel species, for which the name Pseudomonas paralcaligenes sp. nov. is proposed. The type strain is MRCP1333T (=LMG 32254T,=JCM 34250T).
Identifying Neural Signatures of Dopamine Signaling with Machine Learning
Authors: Sorooshyari Siamak K. , Ouassil Nicholas , Yang Sarah J. , Landry Markita P.
Published: January 2023

The emergence of new tools to image neurotransmitters, neuromodulators, and neuropeptides has transformed our understanding of the role of neurochemistry in brain development and cognition, yet analysis of this new dimension of neurobiological information remains challenging. Here, we image dopamine modulation in striatal brain tissue slices with near infrared catecholamine nanosensors (nIRCat) and implement machine learning to determine which features of dopamine modulation are unique to changes in stimulation strength, and to different neuroanatomical regions. We trained a support vector machine and a random forest classifier to determine whether recordings were made from the dorsolateral striatum (DLS) versus the dorsomedial striatum (DMS) and find that machine learning is able to accurately distinguish dopamine release that occurs in DLS from that occurring in DMS in a manner unachievable with canonical statistical analysis. Furthermore, our analysis determines that dopamine modulatory signals including the number of unique dopamine release sites and peak dopamine released per stimulation event are most predictive of neuroanatomy yet note that integrated neuromodulator amount is the conventional metric currently used to monitor neuromodulation in animal studies. Lastly, our study finds that machine learning discrimination of different stimulation strengths or neuroanatomical regions is only possible in adult animals, suggesting a high degree of variability in dopamine modulatory kinetics during animal development. Our study highlights that machine learning could become a broadly-utilized tool to differentiate between neuroanatomical regions, or between neurotypical and disease states, with features not detectable by conventional statistical analysis.
Limits to the spread of an obligate social cheater in the social amoebaDictyostelium discoideum
Authors: Medina James , Queller David , Strassmann Joan
Published: January 2023

Cooperation is widespread across life, but its existence can be threatened by exploitation. Social cheaters can be obligate, incapable of contributing to a necessary function, so that spread of the cheater leads to loss of the function. In the social amoebaDictyostelium discoideum, obligate social cheaters cannot become dead stalk cells that lift spores up for dispersal, but instead depend on forming chimeras with fully functional altruistic individuals for forming a stalk. Obligate cheaters inD. discoideumare known to pay the cost of being unable to form fruiting bodies on their own. In this study we discovered that there are two additional costs that can apply to obligate cheaters. Even when there are wild-type cells to parasitize, the chimeric fruiting bodies that result have shorter stalks that are disadvantaged in spore dispersal. Furthermore, we found that obligate cheaters were overrepresented among spore cells in chimeras only when they were at low frequencies. Failure to develop into viable fruiting bodies on their own, negative frequency-dependent cheating, and shorter fruiting bodies represent three limits on obligate social cheating so it is not surprising that obligate cheaters have not been found in nature.
Altered structural-functional coupling in Parkinson’s disease
Authors: Chen Zhichun , Li Guanglu , Zhou Liche , Zhang Lina , Liu Jun
Published: January 2023

Background

Structural-functional coupling is abnormally altered in a variety of neuropsychiatric disorders and correlates with clinical symptoms of the patients. The relationships between structural-functional coupling and clinical manifestations of Parkinson’s disease (PD) remain unclear.

Objective

The purpose of this study is to investigate whether the structural-functional coupling changes in PD and to explore the clinical implications of this network metric.

Methods

Structural 3D T1-weighted imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were performed in 22 control subjects and 34 PD patients. Two types of structural-functional coupling (node coupling and network coupling) were derived from structural and functional images. The associations between structural-functional network coupling and clinical characteristics and genetic variations of 73 PD patients from Parkinson’s Progression Markers Initiative database were analyzed.

Results

PD patients exhibited reduced structural-functional node couplings in multiple brain networks compared to controls. Structural-functional node coupling could be shaped by age, sex, and disease severity. In addition, this metric was modified byTMEM175rs34311866 andGPNMBrs199347, two genetic variants conferring PD risk. In contrast, network coupling was less affected in PD. Particularly, structural-functional network couplings were potential predictors of motor symptoms, non-motor symptoms and pathological markers of cerebrospinal fluid in PD patients. Additionally, structural-functional network coupling was significantly correlated with metrics of network topology.

Conclusions

Our findings suggest that structural-functional decoupling is an essential network feature in PD and structural-functional network coupling may serve as a valuable trait-like biomarker for disease burden in PD.
Targeting PPT1 with ezurpimtrostat sensitives liver tumor to immunotherapy by switching cold into hot microenvironments
Authors: Bestion Eloïne , Rachid Madani , Tijeras-Raballand Annemilaï , Roth Gael , Decaens Thomas , Ansaldi Christelle , Mezouar Soraya , Raymond Eric , Halfon Philippe
Published: January 2023

Background

Palmitoyl-protein thioesterase-1 (PPT1) is an exciting druggable target for inhibiting autophagy in cancer.

Methods

In this study, we aimed to evaluate the effects of ezurpimtrostat-targeting PPT1 in combination with an anti-PD-1 antibody in liver cancer using a transgenic immunocompetent mouse model.

Results

Herein, we revealed that inhibition of PPT1 using ezurpimtrostat, a safe anticancer drug in humans, decreased the liver tumor burden by inducing the penetration of lymphocytes within tumors when combined with anti-programmed death-1 (PD-1). Inhibition of PPT1 potentiates the effects of anti-PD-1 immunotherapy by increasing the expression of major histocompatibility complex (MHC)-I at the surface of liver cancer cells and modulates immunity through recolonization and activation of cytotoxic CD8+lymphocytes.

Conclusions

Ezurpimtrostat turns cold into hot tumors and, thus, constitutes a powerful strategy to improve T cell-mediated immunotherapies in liver cancer.

Summary box

We reported that inhibiting palmitoyl-protein thioesterase-1 enzyme (PPT1) enhances the antitumor activity of anti-programmed death-1 (PD-1) in liver cancer in preclinical models. This study provides the rational for this combination in cancer clinical trials.

Graphical abstract

Ezurpimtrostat activities in cancer

The absence of immune effectors especially cytotoxic cells in the microenvironment of cold tumor is associated with a lack of response to ICI. This condition is mainly due to an increase in the autophagy process responsible for the sequestration and destruction of an antigen-presenting molecule, MHC-I. The inhibition of PPT1 using ezurpimtrostat treatment led to (1) the inhibition of PPT1 and consequently the autophagy process, (2) the increase of MHC-I surface expression, and (3) the recruitment and the activation of CD8+T cells at tumor site leading to (4) the improvement of CD8+T cell cytotoxic activity. Thus, ezurpimtrostat-treated tumors become eligible for anti-PD-1 immunotherapy as the combination of both led to decreased macronodules, micronodules, and tumor growth.
Human Bone Marrow Plasma Cell Atlas: Maturation and Survival Pathways Unraveled by Single Cell Analyses
Authors: Duan Meixue , Nguyen Doan C. , Joyner Chester J. , Saney Celia L. , Tipton Christopher M. , Andrews Joel , Lonial Sagar , Kim Caroline , Hentenaar Ian , Kosters Astrid , Ghosn Eliver , Jackson Annette , Knechtle Stuart , Maruthamuthu Stalinraja , Chandran Sindhu , Martin Tom , Rajalingam Raja , Vincenti Flavio , Breeden Cynthia , Sanz Ignacio , Gibson Greg , Eun-Hyung Lee F.
Published: January 2023

Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4. Additional clusters included early and late IgM-predominant ASC of likely extra-follicular origin; IFN-responsive; and high mitochondrial activity ASC. Late ASCs were distinguished by differences in G2M checkpoints, MTOR signaling, distinct metabolic pathways, CD38 expression, and utilization of TNF-receptor superfamily members. They mature through two distinct paths differentiated by the degree of TNF signaling through NFKB. This study provides the first single cell resolution atlas and molecular roadmap of LLPC maturation, thereby providing insight into differentiation trajectories and molecular regulation of these essential processes in the human BM microniche. This information enables investigation of the origin of protective and pathogenic antibodies in multiple diseases and development of new strategies targeted to the enhancement or depletion of the corresponding ASC.

One Sentence Summary:The single cell transcriptomic atlas of human bone marrow plasma cell heterogeneity shows maturation of class-switched early and late subsets, specific IgM and Interferon-driven clusters, and unique heterogeneity of the late subsets which encompass the long-lived plasma cells.
Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs
Authors: Ernest Jacqueline P. , Ni Goh Janice Jia , Strydom Natasha , Wang Qianwen , van Wijk Rob C. , Zhang Nan , Deitchman Amelia , Nuermberger Eric , Savic Rada M.
Published: January 2023

Background

Phase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum colony forming units (CFU) over 14 days, as the primary outcome for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from 7 to 19.6 million dollars on average, while more than 30% of drugs fail to progress to phase 3. Better utilizing preclinical data to predict and prioritize the most likely drugs to succeed will thus help accelerate drug development and reduce costs. We aim to predict clinical EBA using preclinical in vivo pharmacokinetic-pharmacodynamic (PKPD) data and a model-based translational pharmacology approach.

Methods and Findings

First, mouse PK, PD and clinical PK models were compiled. Second, mouse PKPD models were built to derive an exposure response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PKPD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations.

Conclusion

This platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.
Trends in patient attachment to an aging primary care workforce: a population-based serial cross-sectional study in Ontario, Canada
Authors: Premji Kamila , Green Michael E , Glazier Richard H , Khan Shahriar , Schultz Susan E , Mathews Maria , Nastos Steve , Frymire Eliot , Ryan Bridget L
Published: January 2023

Background

Population aging is a global phenomenon. Resultant healthcare workforce shortages are anticipated. To ensure access to comprehensive primary care, which correlates with improved health outcomes, equity, and costs, data to inform workforce planning are urgently needed.

Objectives

To explore temporal trends in early career, mid-career, and near-retirement comprehensive primary care physician characteristics, the medical and social needs of their patients, and the workforce’s capacity to absorb patients of near-retirement physicians. Gender-based workforce trends and trends around alternative practice models were also explored.

Design

A serial cross-sectional population-based study using health administrative data.

Setting

Ontario, Canada, where most comprehensive primary care is delivered by family physicians (FPs) under universal insurance.

Participants

All insured Ontario residents at three time points: 2008 (12,936,360), 2013 (13,447,365), and 2019 (14,388,566) and all Ontario physicians who billed primary care services (2008: 11,566; 2013: 12,693; 2019: 15,054).

Exposure(s)

Changes in the comprehensive FP workforce over three time periods.

Main Outcome(s) and Measure(s)

The number and proportion of patients attached to near-retirement comprehensive FPs; the number and proportion of near-retirement comprehensive FPs; the characteristics of patients and their comprehensive FPs.

Results

Patient attachment to comprehensive FPs increased over time. The overall FP workforce grew, but the proportion practicing comprehensiveness declined from 77.2% (2008) to 70.7% (2019), with shifts into other/focused scopes of practice across all physician career stages. Over time, an increasing proportion of the comprehensive FP workforce was near retirement age. Correspondingly, an increasing proportion of patients were attached to near-retirement comprehensive FPs. By 2019, 13.9% of comprehensive FPs were 65 years or older, corresponding to 1,695,126 (14.8%) patients. Mean patient age increased, and near-retirement comprehensive FPs served markedly increasing numbers of medically and socially complex patients.

Conclusions and Relevance

Primary care is foundational to high-performing health systems, but the sector faces capacity challenges as both patients and physicians age and fewer physicians choose to practice comprehensiveness. Nearly 15% (1.7 million) of Ontarians with a comprehensive FP may lose their physician to retirement by 2025. To serve a growing and increasingly complex patient population, innovative solutions that extend beyond simply growing the FP workforce are needed.
Comparative study of the short-range structure of α-V2O5, α-TeO2 and xV2O5–(100 − x)TeO2 glasses using X-ray diffraction, Rietveld analysis and reverse Monte Carlo simulations
Authors: Kaur Navjot , Khanna Atul , Kaur Puneet , Singh M. N. , Sinha A. K.
Published: January 2023

Vanadium–tellurite glasses, tetragonal TeO2 and orthorhombic V2O5 crystalline samples were characterized for their atomic structure properties by synchrotron X-ray diffraction, pair distribution function analysis, reverse Monte Carlo simulations (RMC) and Rietveld analysis. The pair correlation function, G(r), of V2O5 shows the first peak at 1.61 Å. G(r) of TeO2 shows three peaks at 1.57, 2.13 and 2.88 Å due to Te–O linkages of three different lengths, whereas the Te–Te atomic pair correlation shows a peak at 3.85 Å. The average coordination number of V with O in crystalline V2O5 is 4.39 while that of Te with O in crystalline TeO2 is 3.71. G(r) of the vanadium tellurite glass shows the first peak at 1.90 Å due to overlapping Te–O and V–O atomic pair correlations. The RMC analysis on diffraction data of glasses found that the V–O coordination number is in the range 5.27–5.59 and the Te–O coordination number is 5.39–5.67. However, it is found that these coordination numbers cannot be clearly defined due to short-range disorder.
Analysis of ATC-related aviation accidents and incidents
Authors: Nikšić Lejla , Arıkan Öztürk Ebru
Published: January 2023

Purpose

This study aims to analyse the air traffic control (ATC)-related accidents and incidents. The paper aims to determine technical, operational and environmental factors that influence ATC-related accidents and incidents. This is important to reduce the number of these accidents.

Design/methodology/approach

This predictive and dipendence study investigated situational factors indicated in the data sets of National Transportation Safety Board (NTSB) and European Union Aviation Safety Agency (EASA) (for the period 2008–2018). The specific factors were time of day in which accident occurred, location, air traffic management (ATM) contribution, flight rules, ATC unit and outside factors. Logistic regression was used to differentiate factors between fatal ATC-related accidents versus ATC-related incidents. Further, by using Pearson’s chi-squared test, significant relationships between all factors in ATC-related accidents and ATC-related incidents were identified.

Findings

The results showed that five factors of total six factors – ATM contribution, flight rules, ATC unit, outside factors and aircraft location – influence to ATC-related accidents and incidents. Further, results showed significant relationships between each all factors in ATC-related accidents and incidents. According to that, differences and similitudes are presented.

Originality/value

After more than 20 years, study about ATC-related accidents and incidents was necessary to establish changements in thıs type of accidents. Belong of that, this is the first study that used data sets of both, NTSB and EASA, to determine the factors that affect ATC-related accidents and incidents.
Gender and financial literacy in Ghana
Authors: Sarpong-Kumankoma Emmanuel , Ab-Bakar Sayeed , Akplehey Felix Nartey
Published: January 2023

Purpose

This study examines the gender gap in financial literacy in Ghana.

Design/methodology/approach

This study employs primary data and probit models together with the Oaxaca-Blinder decomposition strategy.

Findings

The authors found that males are generally more financially literate than females are. The results also show that much of the gender gap in financial literacy is explained by differences in coefficients or how literacy is produced and not by differences in the demographic and socio-economic characteristics of men and women. Thus, the gap may be attributable to unobserved behavioural and psychological traits, as well as cultural and social norms regarding gender roles in financial decision-making.

Practical implications

It is evident that further action is needed to bridge the gap between men and women with regards to financial literacy. Effective interventions may include improving women's access to financial information and education, as well as encouraging their participation in household financial decision-making and planning. In particular, less educated women need to be targeted by policy initiatives in this regard.

Originality/value

This study contributes to the scant literature on gender gap in financial literacy in developing countries.
Differences in consumers' perceptions based on the description order/amount of benefit–risk information on foods: a randomized comparative survey in Japan
Authors: Tanemura Nanae , Kakizaki Masako , Kusumi Takashi , Onodera Rie , Tominaga Yoshiko , Araki Michihiro , Chiba Tsuyoshi
Published: January 2023

Purpose

In this study, the authors clarified the differences in consumers' benefit–risk perceptions based on changes (description order and amount) in the benefit–risk information after an assessment of the health impact of foods.

Design/methodology/approach

The authors set the following four benefit–risk information groups relating to fatty fish consumption—Group 1: benefit/simple–risk/detail; Group 2: risk/detail–benefit/simple; Group 3: benefit/detail–risk/detail; Group 4: risk/detail–benefit/detail. The authors conducted a randomized controlled study on June, 2022, involving 7,200 Japanese consumers aged over 18 years.

Findings

There were no significant differences in the risk and benefit perceptions. Furthermore, the logistic regression analysis identified women and benefit perception as significant influencing factors of “no-risk acceptance.”

Originality/value

This study found that all four message formats were acceptable to consumers due to high-benefit/low-risk perceptions. However, despite the difference in message types used in benefit–risk communication, there was no effect on risk acceptance among consumers. Public agencies should design their communication with considerations toward women and benefit perceptions.
Employment status and financial resilience during the COVID-19 pandemic
Authors: Yao Rui , Zhang Jie
Published: January 2023

Purpose

The purpose of this study is to examine the association between employment status and financial resilience during the COVID-19 pandemic.

Design/methodology/approach

This study employed US nationally representative data. A financial resilience index was created based on households' ability to pay for basic living expenses and the resources used to meet such needs. Employment status was categorized into seven groups based on whether the respondent worked for pay in the last seven days, experience of income shock since the start of the pandemic for workers' household and reasons for not working for non-workers' household. A generalized linear model (GLM) model was used to examine the relationship between respondent employment status and household financial resilience. An ordinary least square (OLS) logistic regression with no proportional odds assumption was employed to investigate the association between the respondent's employment status and household ability to pay for basic living expenses. A logistic regression was utilized to explore the relationship between respondent employment status and resources used by the household to pay for basic living expenses.

Findings

The top three least financially resilient households include those in which the respondent's work was affected by the pandemic, the respondent did not work due to being sick with COVID or caring for someone with COVID and the respondent did not work due to fear of COVID.

Research limitations/implications

Future research should distinguish the reasons for not working when examining the association between unemployment and household financial resilience as well as their overall financial wellbeing. Cross-sectional data cannot establish a causal relationship. Findings using US data may not be generalized to other countries.

Practical implications

Workers with health and employment risks and financial professionals working with these clients should consider these risks when building household financial safety net. Policymakers should develop measures to allow normal business operations while effectively contain the spread of the COVID-19 virus.

Originality/value

This study created a financial resilience index that considers various household situations, allows both internal and external resources to be utilized to cover basic living expenses and reflects the diverse nature of financial resilience. This study is the first to look into voluntary and involuntary labor force separation for COVID-19 and non-COVID-19 related reasons.
The effects of brand relationships on justice perceptions in service recovery
Authors: Filho Cid Gonçalves , Kiefer Kip , Fetscherin Marc , Blandina Alexander , Rocha Marcelo Nacif , Monteiro Plínio Rafael Reis
Published: January 2023

Purpose

This paper aims to explore how brand relationship quality (BRQ) influences consumers’ perceived sense of justice in the context of service recovery situations.

Design/methodology/approach

The authors conducted a survey of 368 Brazilian consumers who experienced real-life automotive service recovery situations. The authors tested their model and underlying hypotheses using structural equation modeling.

Findings

Stronger BRQ led to higher levels of perceived justice (distributive, procedural and interactional), which in turn led to higher customer satisfaction of complaint handling. Ultimately, higher customer satisfaction led to lower complaining, lower retaliation and higher purchase intention. The authors' alternative model tested the effects of BRQ sub-dimensions on justice perception. Interestingly, trust produced a “love-is-blind” effect, while intimacy revealed a “love-becomes-hate” effect.

Originality/value

This study assessed BRQ and its sub-dimensions (self-connection, satisfaction, commitment, trust and intimacy) on sense of justice (distributive, procedural and interactional) within service recovery. Also, this study demonstrated the opposing effects of the brand relationship sub-dimensions trust and intimacy on perceptions of justice.
Insider trading laws to counter financial crime: a comparative study of Mauritius, UK and US laws
Authors: Beebeejaun Ambareen
Published: January 2023

Purpose

The rise in business activities coupled with free trade liberalisation across countries has entailed an increase in securities transaction as well as insider trading (IT). In fact, IT is characterised by the influence and usage of some prior knowledge concerning sensitive information of a corporate body which results in a financial benefit to the insider trader. The practice of IT is not only unethical but also illegal and this statement is witnessed by the mushrooming of laws across the globe categorising IT as an offence. However, the type of punishment varies in different countries depending on various factors. Consequently, the purpose of this paper is to assess the adequacy and efficiency of IT laws in the context of a developing country being Mauritius.

Design/methodology/approach

To achieve the research objective, the Mauritian laws on IT were compared with the corresponding laws of some developed countries like the USA and the UK. As such, a qualitative research method was adopted. In particular, the black letter approach was used to examine the relevant laws of Mauritius, UK and USA on IT. A comparative analysis was conducted concerning IT laws for each country with the view of suggesting recommendations for Mauritian stakeholders to adopt to enhance the existing legal and regulatory framework on IT.

Findings

It was found that Mauritian IT laws are largely inspired from both the US and UK corresponding legislation. However, Mauritian laws need to be strengthened by imposing some more severe penalties in terms of fines and terms of imprisonment like the USA has established. The Mauritian Financial Services Commission as the regulator also needs to play a more active role in disseminating particularities of IT laws, offences and penalties to the civil society at large.

Originality/value

At present, this study will be among the first academic writings on the efficiency of IT laws in Mauritius and also, because existing literature is quite scarce on assessing the adequacy of IT legislation in developing countries, this research aims at filling in the gap in literature. The study is carried out with the aim of combining a large amount of empirical, theoretical and factual information that can be of use to various stakeholders and not only to academics.