bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of nutrition education based on PRECEDE model on iron deficiency anemia among female students
Authors: Khani Jeihooni Ali , Hoshyar Sanaz , Afzali Harsini Pooyan , Rakhshani Tayebeh
Published: June 2021

Background

Iron deficiency anemia disrupts the concentration of adolescent girls; reduces their academic achievement, productivity, and physical strength, and increases the risk of infection. This research aim was to evaluate the effectiveness of the PRECEDE model nutrition education on iron deficiency anemia among female students of Fasa City, Fars Province, Iran.

Methods

This quasi-experimental study was done on 160 students (80 experimental and 80 control groups) who were selected using a random sampling method in Fasa City, Fars Province, Iran, in 2018–2019. The educational intervention included six sessions based PRECEDE model for 45 or 50 min. A scale of this study consisted of two parts; demographic information, and PRECEDE constructs were used to determine the nutritional behaviors status concluding preventing iron deficiency anemia and hemoglobin, hematocrit, and ferritin blood level in two (before and 4 months after intervention) times.

Results

In the experimental group of the students the mean age was 13.85 + 1.72 years and in the controlled group was 13.60 + 1.81 years. Moreover, there was no significant difference in the PRECEDE constructs, and nutritional behaviors preventing iron deficiency anemia before the intervention in two groups of study. However, the experimental group showed a significant increase 4 months after the intervention. Also, there was no significant difference in the mean score of hemoglobin, hematocrit, and ferritin blood level between the two groups before the intervention. However, in ferritin level, a significant increase was shown in 4 months after the intervention in the experiential group.

Conclusions

Based on results, the nutrition intervention education base on PRECEDE model has a positive effect to improve iron deficiency anemia preventive behaviors in female students.
Factors impacting hospital avoidance program utilisation in the care of acutely unwell residential aged care facility residents
Authors: Testa Luke , Ryder Tayhla , Braithwaite Jeffrey , Mitchell Rebecca J.
Published: June 2021

Background

An existing hospital avoidance program, the Aged Care Rapid Response Team (ARRT), rapidly delivers geriatric outreach services to acutely unwell or older people with declining health at risk of hospitalisation. The aim of the current study was to explore health professionals’ perspectives on the factors impacting ARRT utilisation in the care of acutely unwell residential aged care facility residents.

Methods

Semi-structured interviews were conducted with two Geriatricians, two ARRT Clinical Nurse Consultants, an ED-based Clinical Nurse Specialist, and an Extended Care Paramedic. Interview questions elicited views on key factors regarding care decisions and care transitions for acutely unwell residential aged care facility residents. Thematic analysis was undertaken to identify themes and sub-themes from interviews.

Results

Analysis of interviews identified five overarching themes affecting ARRT utilisation in the care of acutely unwell residents: (1) resident care needs; (2) family factors; (3) enabling factors; (4) barriers; and (5) adaptability and responsiveness to the COVID-19 pandemic.

Conclusion

Various factors impact on hospital avoidance program utilisation in the care of acutely unwell older aged care facility residents. This information provides additional context to existing quantitative evaluations of hospital avoidance programs, as well as informing the design of future hospital avoidance programs.
Triglyceride-glucose index in the development of peripheral artery disease: findings from the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Gao Jing-Wei , Hao Qing-Yun , Gao Ming , Zhang Kun , Li Xiong-Zhi , Wang Jing-Feng , Vuitton Dominique A. , Zhang Shao-Ling , Liu Pin-Ming
Published: June 2021

Background

It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).

Methods

We included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987–1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.

Results

Over a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049–1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028–1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132–1.740) and 1.742 (1.294–2.344), respectively] after multivariate adjustments for traditional PAD risk factors.

Conclusions

Higher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.

Trial registration: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.
Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment
Authors: Sharifi-Rad Javad , Quispe Cristina , Butnariu Monica , Rotariu Lia Sanda , Sytar Oksana , Sestito Simona , Rapposelli Simona , Akram Muhammad , Iqbal Mehwish , Krishna Akash , Kumar Nanjangud Venkatesh Anil , Braga Susana S. , Cardoso Susana M. , Jafernik Karolina , Ekiert Halina , Cruz-Martins Natália , Szopa Agnieszka , Villagran Marcelo , Mardones Lorena , Martorell Miquel , Docea Anca Oana , Calina Daniela
Published: June 2021

The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.
Effect of α-tocopheryloxy acetic acid, a vitamin E derivative mitocan, on the experimental infection of mice with Plasmodium yoelii
Authors: Kawamura Kasumi , Kume Aiko , Umemiya-Shirafuji Rika , Kasai Shunji , Suzuki Hiroshi
Published: June 2021

Background

Malaria parasites are known to be vulnerable to oxidative stress. In this study, the effects of the administration of α-tocopheryloxy acetic acid (α-TEA), which is a vitamin E analogue mitocan, on Plasmodium yoelii infection in mice were examined.

Methods

Alpha-TEA was mixed with diet and fed to C57BL/6J mice before and/or after infection. For parasite infection, 4 × 104 red blood cells infected with P. yoelii (strain 17XL) were inoculated by intraperitoneal injection. In another series of experiment, the effect of the oral administration of α-TEA on P. yoelii 17XL infection in mice was examined. Finally, the combined effect of α-TEA and dihydroartemisinin or chloroquine on P. yoelii 17XL infection was examined.

Results

When 0.25% α-TEA was mixed with the diet for 7 days before infection and 14 days after infection (in total for 21 days), for 14 days after infection, and for 11 days from the third day after infection, all P. yoelii 17XL-infected mice survived during the observation period. However, all control mice died within 12 days after infection. These results indicated that α-TEA functions effectively even when administered post-infection. The oral administration of α-TEA for P. yoelii 17XL infection was also significant. Although the infected mice in the solvent control died within 10 days after infection, 90% of the mice infected with P. yoelii 17XL survived during the observation period when treated with 10 mg/head/day of α-TEA for 3 days from day 3 after infection. Although the combined effect of α-TEA and dihydroartemisinin (DHA) or chloroquine on P. yoelii 17XL infection was significant, no synergistic or additive effects were observed from the survival curve.

Conclusions

This study showed the beneficial effects of α-TEA on the experimental infection of mice with P. yoelii 17XL. The stimulatory action of α-TEA on mitochondria and the accompanying reactions, such as reactive oxygen species production, and induction of apoptosis might have some effect on malarial infection.
SERCAP: is the perfect the enemy of the good?
Authors: White Nicholas J. , Nosten François H.
Published: June 2021

Single Encounter Radical Cure and Prophylaxis (SERCAP) describes an ideal anti-malarial drug that cures all malaria in a single dose. This target product profile has dominated anti-malarial drug discovery and development over the past decade. The operational advantage of a single encounter has to be balanced against the need for a high dose, reliable absorption, little variability in pharmacokinetic properties, slow elimination (to ensure curative drug exposures in all patients) and a very low rate of vomiting. The demanding aspirational target may have hindered anti-malarial drug development. Aiming for three-day regimens, as in current anti-malarial treatments, would be better.
Development and validity assessment of a Japanese version of the Exercise Adherence Rating Scale in participants with musculoskeletal disorders
Authors: Takasaki Hiroshi , Kawazoe Shota , Miki Takahiro , Chiba Hiroki , Godfrey Emma
Published: June 2021

Background

Exercise adherence is important for achieving a long-term effect from musculoskeletal management. The Exercise Adherence Rating Scale (EARS), which was developed in 2017 as a patient reported outcome measure to assess exercise adherence in those with chronic low back pain in the UK, has demonstrated acceptable validity and reliability and is a robust measure of exercise adherence. This study aimed to undertake cross-cultural adaptation of the EARS into Japanese and investigate its structural validity in participants with musculoskeletal disorders.

Methods

The current study was composed of two phases, where a provisional Japanese version of the EARS was developed employing an international guideline for cross-cultural adaptation (Phase A), and structural validity was then evaluated using the Rasch analysis (Phase B). Participants with musculoskeletal disorders who have individualized home exercises prescribed by a physical therapist were recruited.

Results

In Phase A, the pilot testing was conducted twice because the initial testing detected some uncertainty revealed in comments from 17 participants (5 males and 12 females, 18–79 years of age) about which activities and exercises were supposed to be included. We therefore modified the draft by identifying a person who prescribed/recommended activities and exercises as per the Working Alliance Inventory. The second pilot testing using this draft recruited 30 participants (6 males and 24 females, 18–79 years of age), who provided no further comments, demonstrating the Japanese version of the EARS (EARS-J) had been successfully developed. In Phase B, data from 200 participants who completed the EARS-J (63 males and 127 females, mean ± SD of age = 53.6 ± 17.0) were analyzed using the Andrich's Rating Scale Model. Rasch statics indicated unidimensionality of the six items of the EARS-J. The Cronbach α was 0.77. Substantial ceiling effect (21.0%) was observed, with no floor effect (0.5%).

Conclusions

A Japanese version of the EARS has been developed, which demonstrated acceptable structural validity with the evidence of unidimensionality in the Rasch analysis in Japanese people with musculoskeletal disorders who were prescribed individualized home exercises. However, there was a substantial ceiling effect and further studies are required to comprehensively establish validity and reliability of the EARS-J.
Impact of day care services on physical and cognitive functions in old people with dementia in a medical center in central Taiwan
Authors: Lin Cheng-Fu , Wu Jia-Jyun , Huang Yu-Hui , Ju Li-Ying , Lin Shih-Yi , Chou Ying-Chyi , Lin Chu-Sheng
Published: June 2021

Background

Day care service (DCS) provides various activities in a professional environment to meet the old people with functional limitations. However, relatively little is known about the effects of DCS on physical and mental functions.

Methods

This was a retrospective study that we used a comprehensive geriatric assessment to evaluate the changes before and after DCS among participants in a hospital-affiliated geriatric day care center in Taiwan. The burden of the participants’ families was also assessed.

Results

The 18 participants with a median age of 80.9 (interquartile range (IQR) 75.2–86.6 y/o) were enrolled and followed up for 6 months. Based on the clinical dementia rating (CDR), disease stage was very mild in 3 participants, mild in 10, moderate in 3, and severe in 2. The activities of daily living (ADL) scores of the participants improved significantly from 75 (IQR 60.0–80.0) at baseline to 77.5 (IQR 65.0–90.0) at the 6 month (p < 0.001), and mini-mental state examination (MMSE) scores from 15 (IQR 11.5–20.0) to 18 (IQR 15.8–24.0) (p = 0.026). There was a positive correlation of baseline mini-nutritional assessment-short form score and the 3-level version of the European Quality of Life-5 dimensions utility index with both ADL and MMSE scores at the 6-month follow-up. In addition, the family burden scale was reduced from 22 to 15 (p = 0.002).

Conclusions

The physical and cognitive functions in old people with dementia who received DCS were maintained or partially improved, and their families’ stress burden was alleviated.
A systematic mapping review of factors associated with willingness to work under emergency condition
Authors: Nafar Hamideh , Tahmazi Aghdam Emir , Derakhshani Naser , Sani’ee Nadia , Sharifian Sakineh , Goharinezhad Salime
Published: June 2021

Introduction

An effective response to an emergency situation relies on health care workers’ preparedness. The main purpose of this study was to provide a comprehensive overview of relevant studies regarding the willingness to work in emergency and disaster situations, describe and classify the most important challenges and solutions, identifying knowledge gaps in the literature which could inform future research.

Methods

In this Systematic Mapping Review required information was searched from PubMed, Scopus, the web of science, Embase databases, and Google scholar search engine in the period 2000–2020. Data were analyzed using a content framework analysis.

Results

From 2902 article search results, 26 articles met the inclusion criteria. The studies varied in terms of aim, study design, and detail of reporting. The results showed that nearly three-quarters of studies were conducted in high and middle-income countries. Most of the studies were published in 2020 due to the COVID-19 pandemic. Also, the most common types of crises reported in the included studies were emerging and re-emerging infectious diseases. The results show that most of the problems were in the dimension of mental and psychological issues, personnel health concerns, and management relationship with personnel.

Conclusion

This mapping review illustrated a big picture of health workers' resilience in disaster conditions. This review presents an overview of different kinds of strategies that address the challenges.

One of the most important challenges in health workforce retention is poor communication between managers and staff. Being away from family, which leads to mental fatigue, puts staff in moral dilemmas. Attracting adequate health professionals, especially volunteers and regulating the shifts of health personnel in crisis time will largely prevent burnout.
PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort
Authors: Santini Daniele , Zeppola Tea , Russano Marco , Citarella Fabrizio , Anesi Cecilia , Buti Sebastiano , Tucci Marco , Russo Alessandro , Sergi Maria Chiara , Adamo Vincenzo , Stucci Luigia S. , Bersanelli Melissa , Mazzaschi Giulia , Spagnolo Francesco , Rastelli Francesca , Giorgi Francesca Chiara , Giusti Raffaele , Filetti Marco , Marchetti Paolo , Botticelli Andrea , Gelibter Alain , Siringo Marco , Ferrari Marco , Marconcini Riccardo , Vitale Maria Giuseppa , Nicolardi Linda , Chiari Rita , Ghidini Michele , Nigro Olga , Grossi Francesco , De Tursi Michele , Di Marino Pietro , Pala Laura , Queirolo Paola , Bracarda Sergio , Macrini Serena , Gori Stefania , Inno Alessandro , Zoratto Federica , Tanda Enrica T. , Mallardo Domenico , Vitale Maria Grazia , Talbot Thomas , Ascierto Paolo A. , Pinato David J. , Ficorella Corrado , Porzio Giampiero , Cortellini Alessio
Published: June 2021

Background

The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy.

Methods

The present analysis aims to describe clinicians’ attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy.

Results

Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p < 0.0001) and with a higher burden of disease (69.3% vs 59.4%, p = 0.0266). In total, 35 patients (6.2%) started ICIs within 30 days of death; among them there was a higher proportion of patients with ECOG-PS ≥ 2 (45.7% vs 14.5%, p < 0.0001) and with a higher burden of disease (82.9% vs 60.9%, p = 0.0266). Primary tumors were significantly different across subgroups (p = 0.0172), with a higher prevalence of NSCLC patients (80% vs 60.9%) among those who started ICIs within 30 days of death. Lastly, 123 patients (21.7%) started ICIs within 3 months of death. Similarly, within this subgroup there was a higher proportion of patients with ECOG-PS ≥ 2 (29.3% vs 12.8%, p < 0.0001), with a higher burden of disease (74.0% vs 59.0%, p = 0.0025) and with NSCLC (74.0% vs 58.8%, p = 0.0236).

Conclusion

Our results confirmed a trend toward an increasing ICIs prescription in frail patients, during the late stages of life. Caution should be exercised when evaluating an ICI treatment for patients with a poor PS and a high burden of disease.
Respiratory Disease Occupational Biomonitoring Collaborative Project (ROBoCoP): A longitudinal pilot study and implementation research in the Parisian transport company
Authors: Guseva Canu I. , Hemmendinger M. , Sauvain J. J. , Suarez G. , Hopf N. B. , Pralong J. A. , Ben Rayana T. , Besançon S. , Sakthithasan K. , Jouannique V. , Debatisse A.
Published: June 2021

The ROBoCoP project is launched within the EU COST Action CA16113 “CliniMARK” aiming to increase the number of clinically validated biomarkers and focused on chronic obstructive pulmonary disease (COPD) biomarker development and validation. ROBoCoP encompasses two consecutive studies consisting of a pilot study followed by a field study. The pilot study is a longitudinal exposure assessment and biomarker study aiming at: 1-understanding the suitability of the candidate biomarkers in surveying populations at risk such as workers exposed to COPD causing agents; 2-determining the best sampling plan with respect to the half-life of the candidate biomarkers; 3-implementing and validating the sampling procedures and analytical methods; 4-selecting the best suitable biomarkers to be measured in the field. Each study participant is surveyed every day during the 6–8 h work-shifts for two consecutive weeks. The field study has an implementation research designe that enabled us to demonstrate the applicability of the standardized protocol for biomarker measurements in occupational settings while also assessing the biomarkers’ validity. ROBoCoP will focus on particulate matter (PM) exposure measurements, exposure biomarkers and a series of effect biomarkers, including markers of lipoperoxidation: 8-isoprostane, malondialdehyd in exhaled breath condensate (EBC) and urine, potential markers of nitrosative stress: NO2−, NO3− and formate anion in EBC; markers of DNA oxidation: 8-hydroxy-2’deoxyguanosine in EBC and urine, marker of genotoxicity: micronuclei in buccal cells, and oxidative potential in exhaled air (OPEA). OPEA appears particularly promising as a clinical biomarker for detecting COPD, and will be tested independently and as part of a biomarker panel. COPD diagnosis will be performed by an experienced occupational physician according to international diagnostic standards and confirmed by a pulmonologist.

This research will include approximatively 300 underground subway workers randomly selected from the personnel registry of a large Parisian transport company. Underground subways are suggested as the most PM polluted urban transport environment. We believe this occupational exposure is relevant for biomonitoring of workers and early detection of respiratory diseases.
Dosimetry study of three-dimensional print template for 125I implantation therapy
Authors: Chen Enli , Zhang Yuwei , Zhang Hongtao , Jia Chenfei , Liang Yansong , Wang Juan
Published: June 2021

Background

125I seed implantation has been found to show good therapeutic effects on tumors. Recent studies showed that three-dimensional (3D) print template-assisted 125I seed implantation can optimize radiation dose distribution. This study aimed to compare the dose distribution differences in 125I seed implantation among 3D print noncoplanar template- (3DPNCT), 3D print coplanar template- (3DPCT) assisted implantation and traditional free-hand implantation.

Methods

We systematically searched the PubMed, EMbase, Cochrane Library, Wan Fang Med Online, China National Knowledge Infrastructure (CNKI) from the earliest to November 2020 without time or language restrictions. And the references of primary literature were also searched. The outcome measures were dosimetry and operation time. This meta-analysis was carried out using Stata 12.0.

Results

A total of 16 original articles were selected for inclusion. The differences of D90, D100, V90, and V100 values pre- and post-implantation with traditional free-hand implantation showed statistically significant (p < 0.05). The differences of D90, D100, V100, V150, V200, and D2cc of organs at risk (OAR) values pre- and post-implantation with 3D print template showed no statistically significant (p > 0.05). Compared with traditional free-hand implantation without any templates, 3D print template could improve postoperative D90 (Standard mean difference, SMD = 0.67, 95% confidence interval (CI) = 0.35 to 0.98, p < 0.001), D100 (SMD = 0.82, 95%CI = 0.40 to 1.23, p < 0.001), V90 (SMD = 1.48, 95%CI = 0.95 to 2.00, p < 0.001), V100 (SMD = 1.41, 95%CI = 0.96 to 1.86, p < 0.001), and reduce operation time (SMD = − 0.93, 95%CI = − 1.34 to − 0.51, p < 0.001). In three studies, both 3DPNCT and 3DPCT plans were designed for all patients. The prescribed dose and seed activity were same. Pooled analysis of D90, D100, V100, D2cc of OAR, number of seeds and number of needles showed no significant differences between 3DPNCT and 3DPCT groups (p > 0.05). However, in 3DPNCT group, V150 and V200 were increased (SMD = 0.35, 0.49; 95%CI = 0.04 to 0.67, 0.02 to 0.96; p = 0.028, 0.043); the number of through bone needles was reduced (SMD = − 1.03, 95%CI = − 1.43 to − 0.64, p < 0.001).

Conclusions

Compared with traditional free-hand implantation, 3D print template-assisted 125I seeds implantation can optimize dose distribution and reduce the implantation time at the same time. Compared with 3D print coplanar template, 3D print noncoplanar template can increase the volume of high dose within tumor target and is more safer in the respect of puncture route.
In vitro zinc supplementation alters synaptic deficits caused by autism spectrum disorder-associated Shank2 point mutations in hippocampal neurons
Authors: Vyas Yukti , Jung Yewon , Lee Kevin , Garner Craig C. , Montgomery Johanna M.
Published: June 2021

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterised by deficits in social interactions and repetitive behaviours. ASDs have a strong genetic basis with mutations involved in the development and function of neural circuitry. Shank proteins act as master regulators of excitatory glutamatergic synapses, and Shank mutations have been identified in people with ASD. Here, we have investigated the impact of ASD-associated Shank2 single nucleotide variants (SNVs) at the synaptic level, and the potential of in vitro zinc supplementation to prevent synaptic deficits. Dissociated rat hippocampal cultures expressing enhanced green fluorescent protein (EGFP) tagged Shank2-Wildtype (WT), and ASD-associated Shank2 single nucleotide variants (SNVs: S557N, V717F, and L1722P), were cultured in the absence or presence of 10 μM zinc. In comparison to Shank2-WT, ASD-associated Shank2 SNVs induced significant decreases in synaptic density and reduced the frequency of miniature excitatory postsynaptic currents. These structural and functional ASD-associated synaptic deficits were prevented by chronic zinc supplementation and further support zinc supplementation as a therapeutic target in ASD.
PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia
Authors: Govaerts Inge , Prieto Cristina , Vandersmissen Charlien , Gielen Olga , Jacobs Kris , Provost Sarah , Nittner David , Maertens Johan , Boeckx Nancy , De Keersmaecker Kim , Segers Heidi , Cools Jan
Published: June 2021

Background

T cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype that comprises 10–15% of childhood and 20–25% of adult ALL cases. Over 70% of T-ALL patients harbor activating mutations in the NOTCH1 signaling pathway and are predicted to be sensitive to gamma-secretase inhibitors. We have recently demonstrated that selective inhibition of PSEN1-containing gamma-secretase complexes can overcome the dose-limiting toxicity associated with broad gamma-secretase inhibitors. In this study, we developed combination treatment strategies with the PSEN1-selective gamma-secretase inhibitor MRK-560 and other targeted agents (kinase inhibitors ruxolitinib and imatinib; XPO-1 inhibitor KPT-8602/eltanexor) for the treatment of T-ALL.

Methods

We treated T-ALL cell lines in vitro and T-ALL patient-derived xenograft (PDX) models in vivo with MRK-560 alone or in combination with other targeted inhibitors (ruxolitinib, imatinib or KPT-8602/eltanexor). We determined effects on proliferation of the cell lines and leukemia development and survival in the PDX models.

Results

All NOTCH1-signaling-dependent T-ALL cell lines were sensitive to MRK-560 and its combination with ruxolitinib or imatinib in JAK1- or ABL1-dependent cell lines synergistically inhibited leukemia proliferation. We also observed strong synergy between MRK-560 and KPT-8602 (eltanexor) in all NOTCH1-dependent T-ALL cell lines. Such synergy was also observed in vivo in a variety of T-ALL PDX models with NOTCH1 or FBXW7 mutations. Combination treatment significantly reduced leukemic infiltration in vivo and resulted in a survival benefit when compared to single treatment groups.We did not observe weight loss or goblet cell hyperplasia in single drug or combination treated mice when compared to control.

Conclusions

These data demonstrate that the antileukemic effect of PSEN1-selective gamma-secretase inhibition can be synergistically enhanced by the addition of other targeted inhibitors. The combination of MRK-560 with KPT-8602 is a highly effective treatment combination, which circumvents the need for the identification of additional mutations and provides a clear survival benefit in vivo. These promising preclinical data warrant further development of combination treatment strategies for T-ALL based on PSEN1-selective gamma-secretase inhibition.
HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML
Authors: Li Zheng , Wang Fangce , Tian Xiaoxue , Long Jun , Ling Bin , Zhang Wenjun , Xu Jun , Liang Aibin
Published: June 2021

Background:

Leukaemia stem cells (LSCs) are responsible for the initiation, maintenance, and recurrence of acute myeloid leukaemia (AML), an aggressive haematological malignancy associated with drug resistance and relapse. Identifying therapeutic LSC targets is critical to curing AML.

Methods

Bioinformatics databases were used to identify therapeutic LSC targets. The conditional knockout mice were used to analyse the role of HCK in leukaemogenesis or normal haematopoiesis. Colony-forming assays, cell counting, and flow cytometry were used to detect the viability and function of leukaemia cells. RT-PCR, western blotting, and RNA sequencing were used to detect mRNA and protein expression.

Result

HCK is expressed at higher levels in LSCs than in haematopoietic stem cells (HSCs), and high HCK levels are correlated with reduced survival time in AML patients. Knockdown of HCK leads to cell cycle arrest, which results in a dramatic decrease in the proliferation and colony formation in human AML cell lines. Moreover, HCK is required for leukemogenesis and leukaemia maintenance in vivo and in vitro. HCK is necessary for the self-renewal of LSCs during serial transplantation and limiting dilution assay. The phenotypes resulting from HCK deficiency can be rescued by CDK6 overexpression in the human cell line. RNA sequencing and gene expression have demonstrated that HCK may sustain cell cycle entry and maintain the self-renewal ability of LSCs through activating the ERK1/2-c-Myc-CDK6 signalling axis. In contrast, HCK deletion does not affect normal haematopoiesis or haematopoietic reconstruction in mice.

Conclusions

HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML and may be an ideal therapeutic target for eradicating LSCs without influencing normal haematopoiesis.
Pediatric interregional healthcare mobility in Italy
Authors: De Curtis Mario , Bortolan Francesco , Diliberto Davide , Villani Leonardo
Published: June 2021

Background

The analysis of interregional healthcare mobility represents one of the main criteria for evaluating Regional Healthcare Systems, both in terms of its economic-financial relevance and the quality and satisfaction of the services provided. The aim of the study is to analyze healthcare mobility and its associated cost in Italy in 2019 for all children ≤ 14 years of age.

Methods

We collected data from the “Rapporto annuale sull’attività di ricovero ospedaliero – Dati SDO 2019” published by the Italian Ministry of Health. These data represent the tool for collecting information relating to all hospitalization services provided in accredited public and private hospitals present throughout the national territory. We collected data for all Italian regions and clustered them in two geographical areas: Center-North regions and South regions (including Sicily and Sardinia). We have analyzed the magnitude of the mobility of children among regions and in particular from the South to the Center-North and the relative cost of this interregional mobility.

Results

 The hospitalization rate of children residing in the South regions was higher than  that of children residing in the Center-North regions (13.9% vs 12.3%). Children residing in the South were more frequently treated in other regions than those living in the Center-North (11.9% vs 6.9%). Even considering the high complexity hospitalizations, children living in the South more frequently underwent treatment in other regions (21.3% vs 10.5% of the Center-North). The cost of passive mobility amounts to € 103.9 million for the South regions (15.1% of the total hospitalizations’ expenditure) and the 87.1% of this cost refers to the mobility to the hospitals of Center-North. The cost of healthcare migration from South regions to other South regions was much lower (12.9%, equal to € 13.4 million).

Conclusions

Healthcare mobility, while affecting all Italian regions, is particularly relevant in the South regions and indicates a lack of pediatric care, which should be strengthened by creating services that are currently not evenly distributed throughout the territory.
Optimizing expression quantitative trait locus mapping workflows for single-cell studies
Authors: Cuomo Anna S. E. , Alvari Giordano , Azodi Christina B. ,   single-cell eQTLGen consortium, McCarthy Davis J. , Bonder Marc Jan
Published: June 2021

Background

Single-cell RNA sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sample multiplexing improving, population-scale scRNA-seq, and thus single-cell expression quantitative trait locus (sc-eQTL) mapping, is increasingly feasible. Mapping of sc-eQTL provides additional resolution to study the regulatory role of common genetic variants on gene expression across a plethora of cell types and states and promises to improve our understanding of genetic regulation across tissues in both health and disease.

Results

While previously established methods for bulk eQTL mapping can, in principle, be applied to sc-eQTL mapping, there are a number of open questions about how best to process scRNA-seq data and adapt bulk methods to optimize sc-eQTL mapping. Here, we evaluate the role of different normalization and aggregation strategies, covariate adjustment techniques, and multiple testing correction methods to establish best practice guidelines. We use both real and simulated datasets across single-cell technologies to systematically assess the impact of these different statistical approaches.

Conclusion

We provide recommendations for future single-cell eQTL studies that can yield up to twice as many eQTL discoveries as default approaches ported from bulk studies.
Characterization of the gut microbiota in diabetes mellitus II patients with adequate and inadequate metabolic control
Authors: Hamasaki-Matos Angie Joyce , Cóndor-Marín Katherine Marlene , Aquino-Ortega Ronald , Carrillo-Ng Hugo , Ugarte-Gil Cesar , Silva-Caso Wilmer , Aguilar-Luis Miguel Angel , del Valle-Mendoza Juana
Published: June 2021

Objective

The objective of this study was to characterize the composition of the gut microbiota in type 2 Diabetes Mellitus (T2DM) patients with adequate and inadequate metabolic control, and its relationship with fiber consumption.

Results

A total of 26 patients with type 2 diabetes mellitus (T2DM) were enrolled, of which 7 (26.9%) cases had adequate metabolic control (HbA1c < 7%) and 19 (73.1%) inadequate metabolic control (HbA1c ≥ 7%). It was observed that among patients with controlled T2DM, 2 (28.6%) cases presented good intake of fiber and 5 (71.4%) cases a regular intake. In contrast, in patients with uncontrolled T2DM, 13 (68.4%) patients reported a regular intake and 6 (31.6%) a poor intake. In relation to the identification of the gut microbiota, both groups presented a similar characterization. There were differences in the population of bacteria identified in both groups, however, the results were not statistically significant. The most frequently identified bacteria in controlled and uncontrolled T2DM patients were Prevotella (71.4% vs 52.6%), followed by Firmicutes (71.4% vs 42.1%), Proteobacteria (71.4% vs 36.8%) and Bacteroidetes (57.1% vs 37.8%). On the other hand, Fusobacterium, Actinobacteria were not identified in either of the two groups of study.
Analysis on risk factors for neck shortening after internal fixation for Pauwels II femoral neck fracture in young patients
Authors: Zhao Fulong , Guo Lijuan , Wang Xuefei , Zhang Yakui
Published: June 2021

Background

Femoral neck shortening can occur in young patients receiving internal fixation for Pauwels type II femoral neck fracture. The risk factors for neck shortening, which can affect hip function, are not clear. This study aimed to retrospectively identify risk factors for neck shortening after internal fixation with parallel partially threaded cannulated cancellous screws (FPTCS) for Pauwels type II femoral neck fracture in relatively young patients.

Methods

Clinical data from 122 cases with Pauwels type II femoral neck fracture from February 2014 to February 2019 were reviewed and analyzed, and causes of neck shortening were statistically analyzed. And the Chi-squared test or Fisher’s exact test was used to compare indicators. Multivariate analysis was conducted with non-conditional logistic regression analysis.

Results

Statistically significant differences were found in age, sex, BMD, BMI, fracture type, posterior medial cortex comminution, and reduction quality between patients with femoral neck shortening and those without femoral neck shortening. Logistic regression analysis showed that fracture type, posterior medial cortex comminution, and reduction quality were the main risk factors for neck shortening.

Conclusion

Fracture type, posterior medial cortex comminution, and reduction quality can be used as important reference indexes to predict the possibility of neck shortening after internal fixation with FPTCS for Pauwels type II femoral neck fracture in young patients. BMD and BMI may be also risk factors.
The prevalence of Listeria species in different food items of animal and plant origin in Ethiopia: a systematic review and meta-analysis
Authors: Diriba Kuma , Awulachew Ephrem , Diribsa Kuma
Published: June 2021

Background

Listeriosis is one of the important emerging zoonotic disease affecting human health following the consumption of contaminated food of animal origin. It results in serious clinical complications in humans with a high case facility rate. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of Listeria species in Ethiopia.

Methods

A systematic search was conducted on PubMed, Web of Science, EMBASE, Google Scholar and the Cochrane Library. All identified observational studies reporting the prevalence of Listeria species in different food items of animal and plant origin in Ethiopia were included. Three authors independently extracted data and analyzed them using STATA Version 13 statistical software. A random effects model was computed to estimate the pooled prevalence of Listeria species in Ethiopia.

Results

After reviewing 122 studies, five studies fulfilled the inclusion criteria were included in the meta-analysis. The findings from the five studies revealed that the pooled prevalence of Listeria species in different food items of animal and plant origin in Ethiopia was 27% (95% CI 25, 29). The highest prevalence of Listeria species was reported in beef meat followed by ice cream with prevalence rates of 62% (95% CI 50, 75) and 43% (95% CI 33, 53), respectively.

Conclusion

The presence of Listeria species in different food items of animal and plant origin in Ethiopia is an indicator of the presence of public health hazards to the consumer, particularly to the high-risk groups. Hence, awareness creation on food safety and implementation of regulations is strongly recommended.
Lithology identification from well-log curves via neural networks with additional geologic constraint
Authors: Jiang Chunbi , Zhang Dongxiao , Chen Shifeng
Published: June 2021

Lithology identification is of great importance in reservoir characterization. Recently, many researchers have applied machine-learning techniques to solve lithology identification problems from well-log curves, and their works indicate three main characteristics. First, most works predict lithofacies using features measured during logging, whereas very few consider adding stratigraphic sequence information that is available prior to drilling to solve this problem. Second, most studies predict lithofacies using measured properties of one depth point, whereas few take the influence of the neighboring formation into account. Third, due to a lack of publicly available interpreted well-log data, previous research has concentrated on applying different algorithms on their private data set, making it impossible to perform a comparison. We have developed a machine-learning framework to solve the lithology classification problem from well-log curves by incorporating an additional geologic constraint. The constraint is a stratigraphic unit, and we use it as an additional feature. We evaluate three types of recurrent neural networks (RNNs), bidirectional long short-term memory, bidirectional gated recurrent unit (Bi-GRU), and GRU-based encoder-decoder architecture with attention, as well as two types of 1D convolutional neural networks (1D CNNs), temporal convolutional network and multiscale residual network, on a publicly available data set from the North Sea. The RNN-based networks and 1D CNN-based networks can process sequential data, enabling the model to have access to information from neighboring formations when performing lithofacies prediction at a particular depth. Our experiments indicate that geologic constraint improves the performance of the models significantly, and that the overall performance of RNN-based networks is better and more consistent.
Duration of hospital admission in severe mental illness: is longer better?
Authors: Ismail Haitham
Published: June 2021

A Cochrane review has compared short-stay hospital admission with long-stay/standard admission of patients with severe mental illness for a number of outcomes in a total 2030 participants from 6 randomised trials. It reached the conclusion, supported by limited evidence, that short admissions in mental health units do not increase the risk of death, readmission or worsening of mental state, and pose less risk of delayed discharge and patient's unemployment. This commentary examines the available evidence from previous studies and discusses its relevance to current practice.
Investigating associations of childhood abuse and serum brain-derived neurotrophic factor levels with suicidal behaviours in patients with depressive disorders
Authors: Kim Jae-Min , Kim Ju-Wan , Kang Hee-Ju , Lee Ju-Yeon , Kim Sung-Wan , Shin Il-Seon , Chun Byung-Jo , Stewart Robert
Published: June 2021

Background

The role of childhood abuse and serum brain-derived neurotrophic factor (BDNF) levels in suicidal behaviour is controversial.

Aims

We aimed to investigate the individual and interactive effects of the childhood abuse and serum BDNF on suicidal behaviour before and after pharmacologic treatment in patients with depressive disorders.

Method

At baseline, reported childhood emotional, physical and sexual abuse were ascertained and serum BDNF levels were measured in 1094 patients with depressive disorder, 884 of whom were followed during a 1-year period of stepwise pharmacotherapy. Suicidal behaviours evaluated at baseline were previous suicide attempt and baseline suicide severity, and suicidal behaviours evaluated at follow-up were increased suicide severity and fatal/non-fatal suicide attempt. Individual and interactive associations of any childhood abuse and serum BDNF levels with four types of suicidal behaviours were analysed using logistic regression models, after adjusting relevant covariates.

Results

Individual associations of childhood abuse were significant only with previous suicide attempt, and no significant individual associations were found for serum BDNF with any suicide outcome. However, the presence of both childhood abuse and lower serum BDNF levels was associated with the highest prevalence/incidence of all four suicidal behaviours, with significant interactions for baseline suicide severity and fatal/non-fatal suicide attempt during follow-up.

Conclusions

Synergistic interactive effects of child abuse and serum BDNF levels on suicidal behaviours were found before and after pharmacologic treatment in patients with depressive disorders. Information combining childhood abuse and serum BDNF levels could improve predictions of suicidal behaviour in patients with depressive disorders.
Comprehensive Breast Cancer Risk Assessment for CHEK2 and ATM Pathogenic Variant Carriers Incorporating a Polygenic Risk Score and the Tyrer-Cuzick Model
Authors: Gallagher Shannon , Hughes Elisha , Kurian Allison W. , Domchek Susan M. , Garber Judy , Probst Braden , Morris Brian , Tshiaba Placede , Meek Stephanie , Rosenthal Eric , Roa Benjamin , Slavin Thomas P. , Wagner Susanne , Weitzel Jeffrey , Gutin Alexander , Lanchbury Jerry S. , Robson Mark
Published: June 2021

PURPOSE

Breast cancer risks for CHEK2 and ATM pathogenic variant (PV) carriers are modified by an 86-single nucleotide polymorphism polygenic risk score (PRS) and individual clinical factors. Here, we describe comprehensive risk prediction models for women of European ancestry combining PV status, PRS, and individual clinical variables.

MATERIALS AND METHODS

This study included deidentified clinical records from 358,095 women of European ancestry who received testing with a multigene panel (September 2013 to November 2019). Model development included CHEK2 PV carriers (n = 4,286), ATM PV carriers (n = 2,666), and women negative for other breast cancer risk gene PVs (n = 351,143). Odds ratios (ORs) were calculated using multivariable logistic regression with adjustment for familial cancer history. Risk estimates incorporating PV status, PRS, and Tyrer-Cuzick v7.02 were calculated using a Fixed-Stratified method that accounts for correlations between risk factors. Stratification of PV carriers into risk categories on the basis of remaining lifetime risk (RLR) was assessed in independent cohorts of PV carriers.

RESULTS

ORs for association of PV status with breast cancer were 2.01 (95% CI, 1.88 to 2.16) and 1.83 (95% CI, 1.68 to 2.00) for CHEK2 and ATM PV carriers, respectively. ORs for PRS per one standard deviation were 1.51 (95% CI, 1.37 to 1.66) and 1.45 (95% CI, 1.30 to 1.64) in CHEK2 and ATM PV carriers, respectively. Using the combined model (PRS plus Tyrer-Cuzick plus PV status), RLR was low (≤ 20%) for 24.2% of CHEK2 PV carriers, medium (20%-50%) for 63.8%, and high (> 50%) for 12.0%. Among ATM PV carriers, RLR was low for 31.5% of patients, medium for 58.5%, and high for 9.7%.

CONCLUSION

In CHEK2 and ATM PV carriers, risk assessment including PRS, Tyrer-Cuzick, and PV status has the potential for more precise direction of screening and prevention strategies.