bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare seeking among Swedish patients in opioid substitution treatment – a mixed methods study on barriers and facilitators
Authors: Troberg Katja , Lundqvist Karin , Hansson Helena , Håkansson Anders , Dahlman Disa
Published: February 2022

Background

Patients in opioid substitution treatment (OST) have poorer health than the general population. Thus, they do not seek somatic health care to the extent that is medically motivated. Barriers hindering patients from seeking medical help through the conventional healthcare system result in a high degree of unmet healthcare needs. Barriers to, and facilitators of, OST patients’ healthcare seeking have been sparsely examined.

Methods

Mixed methods were employed. The quantitative part consisted of a cross-sectional questionnaire covering questions on physical health, healthcare seeking, and barriers thereof, which was collected from 209 patients in OST. A sub-sample of eleven OST patients participated in semi-structured interviews, for the qualitative part of the study, covering experience of healthcare, lifestyle, and self-images, expectations, and ideals of Swedish healthcare.

Results

Confirmed by qualitative data, quantitative data revealed deprioritization, fear of stigma and of being treated badly, and problems in navigation throughout the healthcare system, leading to unsuccessful establishment of contact, being most common reasons for not seeking somatic healthcare. Thus, interviewees provided a deeper knowledge of the barriers stigma, lack of means to prioritize health and difficulties navigating throughout the healthcare system, leading to resignation and deprioritization. On-site primary healthcare (PHC) seemed to contribute to increased access and utilization of healthcare.

Conclusion

Individual and structural barriers decreasing access to healthcare lead to increased inequalities in healthcare utilization, adding to an already deteriorating health of this ageing population. Integration of on-site primary healthcare and OST could provide acceptable and accessible healthcare.
Acute normovolemic hemodilution in combination with tranexamic acid is an effective strategy for blood management in lumbar spinal fusion surgery
Authors: Li Yang , Zhang Yan , Fang Xiutong
Published: February 2022

Background

The retrospective study was designed to compare the effectiveness and safety of acute normovolemic hemodilution (ANH), tranexamic Acid (TXA), and a combination of ANH and TXA in lumbar spinal fusion surgery.

Methods

Data of 120 patients underwent multi-level posterior spinal fusion for treating degenerative lumbar disease between June 2013 and December 2017 was collected, retrospectively. Four treatment strategies were enrolled, including ANH, TXA, a combination of ANH and TXA, and without any patient blood management. Intraoperative blood loss, hemoglobin and PCV at the end of surgery and at the postoperative first day, and postoperative drain collection, and intraoperative and postoperative transfusion and rate of transfusion were also collected.

Results

Intraoperative blood loss and postoperative drain collection of the TXA group, ANH combined with TXA group were statistically lower than those in the control group and ANH group (P < 0.05). Intraoperative and postoperative transfusion amount and rate of intra-operative allogenic transfusion of the ANH group, TXA group, and ANH combined with TXA group were statistically lower than those of the control group (P < 0.05). Hemoglobin and PCV at postoperative the first day in the ANH group, TXA group, and ANH combined with TXA group were significant higher than those in the control group (P < 0.05). The combination of TXA and ANH group achieved the lowest intraoperative blood loss, postoperative drain collection and allogenic transfusion rate.

Conclusion

A combination of TXA and ANH might be an effective strategy for reducing the rate of transfusion and blood loss in patients underwent lumbar spinal fusion surgery.
Comparison of the fixation ability between lag screw and bone plate for oblique metacarpal shaft fracture
Authors: Chiu Yung-Cheng , Ho Tsung-Yu , Hsu Cheng-En , Ting Yen-Nien , Tsai Ming-Tzu , Hsu Jui-Ting
Published: February 2022

Background

For oblique metacarpal shaft fracture, if anatomical reduction is achieved through conservative cast immobilization rather than stable fixation, bone malrotation can easily occur, resulting in severe loss in hand prehensile function. However, whether bone plate fixation or only lag screw fixation is more preferable remains unclear. Few studies have evaluated whether screw fixation can provide biomechanical fixation strength similar to bone plate fixation.

Objective

We assessed the difference in fixation strength between fixtation with two lag screws and bone plate for oblique metacarpal shaft fractures.

Materials and methods

We created oblique metacarpal shaft fractures on 21 artificial bones and fixated them using (1) double lag screw (2LS group), (2) regular plate (RP group), or (3) locked plate (LP group). To obtain the force–displacement data, a cantilever bending test was conducted for each specimen through a material testing machine. One-way analysis of variance and a Tukey test were conducted to compare the maximum fracture force and stiffness of the three fixation methods.

Results

The maximum fracture force of the 2LS group (mean + SD: 153.6 ± 26.5 N) was significantly lower than that of the RP (211.6 ± 18.5 N) and LP (227.5 ± 10.0 N) groups (p < 0.001). However, no significant differences were discovered between the RP and LP groups. The coefficient of variation for the maximum fracture force of the 2LS group (17.3%) was more than twice as high as that of the RP (8.7%) and LP (4.4%) groups. In addition, the stiffness of the three fixation methods was similar.

Conclusion

Compared with bone plate fixation, double lag screw fixation yielded slightly lower maximum bearable fracture force but similar stiffness. Therefore, this technique could be used for treating oblique metacarpal shaft fractures. However, using double lag screw fixation alone is technically demanding and requires considerable surgical experiences to produce consistent results.
Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression
Authors: Wang Bin , Xu Zhengfeng , Wang Xiuhui , Xia Shengli , Cai Pan , Wang Minghui , Gao Zhenchao
Published: February 2022

Purpose

Osteosarcoma is a type of bone malignancy that mainly occurred in teenagers. This investigation is aimed to clarify the effect of long non-coding RNA (lncRNA) LINC00662 on the proliferation, migration, and invasion in osteosarcoma and explore the underlying action mechanisms.

Methods

The mRNA expression of LINC00662 was determined by real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and transwell assays, respectively. A dual-luciferase reporter assay was used to validate the target relationships Between microRNA (miR)-30b-3p and LINC00662/ ETS domain-containing protein 1 (ELK1). Western blotting was performed to determine the protein expression of ELK1. Xenograft model was established to evaluate the effects of LINC00662 silencing on tumor growth in vivo.

Results

LncRNA LINC00662 and ELK1 were significantly increased, while miR-30b-3p was reduced in osteosarcoma tissues. The results of functional experiments indicated that transfection of small hairpin (sh)-LINC00662 and miR-30b-3p mimics repressed the migration, invasion, and proliferation of osteosarcoma cells. LncRNA LINC00662 also appeared to sponge miR-30b-3p in order to affect the expression of ELK1. Simultaneously, there were weak negative correlations between the expression of miR-30b-3p and LINC00662/ELK1 in osteosarcoma tissues. Rescue experiments suggested that ELK1 overexpression and downregulation of miR-30b-3p reversed the suppressive effects of sh-LINC00662 on the cell migration, invasion, and proliferation in osteosarcoma.

Conclusions

The current study indicated that knockdown of LINC00662 repressed cell migration, invasion, and proliferation through sponging miR-30b-3p to regulate the expression of ELK1 in osteosarcoma. These results may uncover a promising target for the treatment of osteosarcoma.
Anteroinferior bundle of the acromioclavicular ligament plays a substantial role in the joint function during shoulder elevation and horizontal adduction: a finite element model
Authors: Velasquez Garcia Ausberto , Salamé Castillo Farid , Ekdahl Giordani Max , Mura Mardones Joaquin
Published: February 2022

Background

Postoperative acromioclavicular (AC) ligament deficiency has been identified as a common cause of failure after isolated coracoclavicular reconstruction. The two-bundle arrangement of the acromioclavicular ligament has recently been reported in histological and anatomical research. In addition, a clear structural advantage of the superoposterior bundle (SPB) over the less consistent anteroinferior bundle (AIB) was also found. However, the current understanding of the function of the acromioclavicular ligament in joint stability is based on uniaxial bone loading experiments and sequential ligament sectioning. Consequently, these rigid biomechanics models do not reproduce the coupled physiological kinematics, neither in the normal joint nor in the postoperative condition. Therefore, our goal was to build a quasi-static finite element model to study the function of the acromioclavicular ligament based on its biomechanical performance patterns using the benefits of computational models.

Methods

A three-dimensional bone model is reconstructed using images from a healthy shoulder. The ligament structures were modeled according to the architecture and dimensions of the bone. The kinematics conditions for the shoulder girdle were determined after the osseous axes aligned to simulate the shoulder elevation in the coronal plane and horizontal adduction. Three patterns evaluated ligament function. The peak von Mises stress values were recorded using a clock model that identified the stress distribution. In addition, the variation in length and displacement of the ligament during shoulder motion were compared using a two-tailed hypotheses test. P values < 0.01 were considered statistically significant.

Results

The peak von Mises stress was consistently observed in the AIB at 2:30 in coronal elevation (4.06 MPa) and horizontal adduction (2.32 MPa). Except in the position 2:00, statistically significant higher deformations were identified in the two bundles during shoulder elevation. The highest ligament displacement was observed on the Y- and Z-axes.

Conclusions

The AIB has the primary role in restricting the acromioclavicular joint during shoulder motion, even though the two bundles of the AC ligament have a complementary mode of action. During horizontal adduction, the SPB appears to prevent anterior and superior translation.
Incidence and risk factors of preoperative deep venous thrombosis following pelvic and acetabular fractures: a retrospective case–control study
Authors: Zhao Weiguang , Zhao Jianlong , Liu Tiantian , Liu Zhenwu , Liu Li , Zhang Yingze
Published: February 2022

The objective of this study was to investigate the prevalence of preoperative deep venous thrombosis (DVT) in the pelvic cavity and lower extremities following pelvic and acetabular fractures and to identify the risk factors of the occurrence of DVT. Duplex ultrasound (DUS) screening and blood tests were conducted in patients admitted from June 2012 to December 2020 for surgical treatment of pelvic and acetabular fractures. Univariate analyses were performed on data of demographics, comorbidities, time from injury to surgery, injury mechanism, accompanied injury, and laboratory results. The optimal cutoff values of continuous variables with statistical significance were obtained by using the receiver operating characteristic (ROC) curve. A multivariate logistic regression analysis was then employed to examine the independent values in terms of predicting preoperative DVT. A total of 607 patients with pelvic and acetabular fractures were included, among whom 82 (13.5%) patients sustained preoperative DVTs. Specifically, 31.7% (26/82) were diagnosed with proximal DVTs. Fifty-two (63.4%) patients had DVT within 7 days after injury, and 67 (81.7%) patients within 10 days. The multivariate logistic regression analysis identified 6 factors independently associated with the presence of preoperative DVT, including age > 46 years (odds ratio [OR] = 2.94), BMI > 26.73 kg/m2(OR = 3.91), time from injury to surgery > 9 days (OR = 5.39), associated injury (OR = 7.85), ALB < 32.8 g/L (OR = 2.71) and FIB > 3.095 g/L (OR = 3.34). Despite the modern prophylactic regimen, the preoperative DVT in patients with pelvic and acetabular fractures still draws the attention of orthopaedic surgeons. Better understanding these risk factors can help surgeons refine the risk stratification profile and perform early interdisciplinary management for patients at high risk of DVT.
The effect of first- and third-generation prophylactic antibiotics on hospitalization and medical expenditures for cardiac surgery
Authors: Bae Sung-Jin , Kim Inah , Song Jaechul , Chung Euy-Suk
Published: February 2022

Background

This study investigated the efficacy of first-generation (cefazolin) and third-generation (ceftizoxime) prophylactic antibiotics in patients undergoing cardiac surgery and the incidence of surgical site infections, hospitalizations, and medical costs.

Methods

All adult patients (≥ 20 years) undergoing cardiac surgery at one hospital from January 01, 2009, to December 31, 2016, were included in this study. A single prophylactic antibiotic was administered at a dose of 1 g within one hour of the surgical incision and for three days after surgery at eight-hour intervals. After propensity score matching, 194 patients in each antibiotic prophylaxis group (first-generation vs third-generation) were analyzed. Among the 388 patients, the incidence of surgical site infections was compared according to the type of prophylactic antibiotic, and risk factors were evaluated by chi-squared tests followed by multivariate logistic regression analysis.

Results

The incidence of deep surgical site infections was significantly lower in the first-generation group (5.7%) than in the third-generation group (16.5%). The pathogens isolated from the surgical infection sites were similarly distributed in both groups. However, the prevalence of highly infectious gram-positive bacteria was more than that of gram-negative bacteria (67% vs 23%). The preoperative hospitalization duration, mean operation time, and ventilator use time were similar in both groups, but the postoperative hospitalization duration was significantly shorter in the first-generation group (25.5 days) than in the third-generation group (29.8 days). In addition, the medical costs were lower in the first-generation group (20,594 USD) than in the third-generation group (26,488 USD).

Conclusion

In conclusion, the first-generation prophylactic antibiotic was better than the third-generation in reducing surgical site infection rates, hospitalization length, and medical expenditures.
Combination of pseudoephedrine and emodin ameliorates LPS-induced acute lung injury by regulating macrophage M1/M2 polarization through the VIP/cAMP/PKA pathway
Authors: Wang Wen-Ba , Li Jing-Tao , Hui Yi , Shi Jie , Wang Xu-Yan , Yan Shu-Guang
Published: February 2022

Background

Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. This study aimed to investigate the protective effects of pseudoephedrine and emodin combined treatment in experimental ALI, as well as the mechanisms underlying the regulation of inflammation and pulmonary edema via the VIP/cAMP/PKA pathway.

Methods

The wistar rats were randomly divided into fifteen groups (n = 5). Rats in each group were given intragastric administration 1 h before LPS injection. Those in the control and LPS groups were given intragastric administrations of physiological saline, rats in other groups were given intragastrically administered of differential dose therapeutic agents. The rats in the LPS and treatment groups were then injected intraperitoneally with LPS (7.5 mg/kg) to induce ALI. After being treated with pseudoephedrine and emodin for 12 h, all animals were sacrifice. Anal temperatures were taken on an hourly basis for 8 h after LPS injection. Pathological examination of lung specimen was performed by H&E staining. Cytokines (IL-1β, TNF-α, IL-6, iNOS, IL-10, Arg-1, CD86, CD206, F4/80, VIP) in lung tissue were assayed by ELISA and immunofluorescence. The expression of VIP, CAMP, AQP-1, AQP-5, p-PKA, PKA, p-IκBα, IκBα, p-p65, p65, p-P38, P38, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2 protein in lung was determined by western blotting.

Results

After rats being treated with pseudoephedrine + emodin, reduced of fever symptoms. The contents of inflammatory cytokines (IL-1β, TNF-α, IL-6, iNOS) were decreased and anti-inflammatory cytokines (IL-10, Arg-1) were significantly increased in serum. Pseudoephedrine + emodin treatment effectively promoted VIP cAMP and p-PKA protein expression in lung tissues, and significantly inhibited NF-κB, MAPK phosphorylation, Pseudoephedrine + emodin treatment can inhibit M1 polarization and promoted M2 polarization via the VIP/cAMP/PKA signaling pathway.

Conclusions

The combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing VIP/cAMP/PKA signaling. Inhibiting the NF-κB, MAPK inflammatory pathway, relief of pulmonary edema suppressing macrophage M1 polarization, and promoting macrophage M2 polarization.
Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation and suppressing osteoclastogenesis
Authors: Xu Yiming , Xue Song , Zhang Tian , Jin Xinmeng , Wang Cong , Lu Haiming , Zhong Yiming , Chen Hongjie , Zhu Libo , Ma Jinzhong , Sang Weilin
Published: February 2022

Background

Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo.

Methods

LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD.

Results

We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption.

Conclusions

These results showed that TOD can be adopted as a potential therapeutic agent for OA.
Sociodemographic and clinical characteristics of paediatric patients admitted to a neuropsychiatric care hospital in the COVID-19 era
Authors: Gatta Michela , Raffagnato Alessia , Mason Federica , Fasolato Rachele , Traverso Annalisa , Zanato Silvia , Miscioscia Marina
Published: February 2022

Background

Since the first months of 2020, Italy and the world have been facing the COVID-19 pandemic. In addition to the dangerous and potentially deadly effects on physical health, it has caused a radical change in the lifestyle of the population and a potential danger for mental health too. These events were inserted into the context of a growing epidemiological trend regarding children’s psychiatric disorders in the past decade.

Aim

To study the population of patients admitted to a Neuropsychiatric Hospital Unit of North Italy in the first COVID-19 year, comparing them with the population of patients hospitalised during the year immediately before, according to sociodemographic and clinical variables.

Methodology

The study is an observational retrospective cohort. In total, 198 patients hospitalised due to neuropsychiatric problems from February 2019 to March 2021 were recruited. Data were analysed through mean and standard deviation, t-test, percentages, chi square test, and the Fischer exact test.

Results

Risk factors associated with mental health disorders were similar between the two years. The hospitalisation modality showed a decrease in scheduled hospitalisations compared to urgent ones, and among the reasons that led patients to hospitalisation there was a conspicuous increase in eating disorders. More suicidal and self-harming behaviours occurred in the COVID-19 group too, compared to the previous year. The methods used to attempt suicide were changed considerably, with a prevalence of that attempted within the home. Changes in pharmacological therapies also occurred, necessary for more than 80% of inpatients during the COVID year, with a greater use of neuroleptics. There were alarming data about hospitalisation relapses, which increased from 12.2% in the pre-COVID year to 35.0% in the COVID year.

Conclusion

Data shed light on clinical and policy issues in mental health care during the developmental age. Since the COVID-19 health emergency is not yet over, and its effects, especially on mental health, will be long-term, it is necessary to implement services and activities dedicated to both primary and secondary prevention of neuropsychiatric diseases especially during adolescent ages.
PRACT: a pragmatic randomized adaptive clinical trial protocol to investigate a culturally adapted brief negotiational intervention for alcohol use in the emergency department in Tanzania
Authors: Staton Catherine A. , Zadey Siddhesh , O’Leary Paige , Phillips Ashley , Minja Linda , Swahn Monica H. , Hirshon Jon Mark , Boshe Judith , Sakita Francis , Vissoci Joao Ricardo Nickenig , Mmbaga Blandina T.
Published: February 2022

Background

Alcohol use in resource-limited settings results in significant morbidity and mortality. These settings lack the necessary specialty-trained personnel and infrastructure. Therefore, implementing evidence-based interventions from high-income settings, like a brief negotiational intervention (BNI) for alcohol, will require rapid production of evidence of effectiveness to guide implementation priorities. Thus, this study describes a clinical trial protocol to rapidly optimize and evaluate the impact of a culturally adapted BNI to reduce alcohol-related harms and alcohol consumption among injury patients.

Methods

Our pragmatic, adaptive, randomized controlled trial (PRACT) is designed to determine the most effective intervention approach to reduce hazardous alcohol use among adult (≥18 years old) in acute (< 24 h) injury patients. Our culturally adapted, nurse-delivered, intervention (PPKAY) has been augmented with evidence-based, culturally appropriate standards and will be evaluated as follows. Stage 1 of the trial will determine if PPKAY, either with a standard short-message-service (SMS) booster or with a personalized SMS booster is more effective than usual care (UC). While optimizing statistical efficiency, Stage 2 drops the UC arm to compare the PPKAY with a standard SMS booster to PPKAY with a personalized SMS booster. Finally, in Stage 3, the more effective arm in Stage 2 is compared to PPKAY without an SMS booster. The study population is acute injury patients who present to Kilimanjaro Christian Medical Centre, Tanzania, who (1) test alcohol positive by breathalyzer upon arrival; (2) have an Alcohol Use Disorder Identification Test of 8 or above; and/or (3) have reported drinking alcohol prior to their injury. Outcome measures will be evaluated for all arms at 3, 6, 9, 12, and 24 months. The primary outcome for the study is the reduction of the number of binge drinking days in the 4 weeks prior to follow-up. Secondary outcomes include alcohol-related consequences, measured by the Drinker Inventory of Consequences.

Discussion

The findings from this study will be critically important to identify alcohol harm reduction strategies where alcohol research and interventions are scarce. Our innovative and adaptive trial design can transform behavior change research and identify the most effective nurse-driven intervention to be targeted for integration into standard care.

Trial registration

ClinicalTrials.govNCT04535011. Registered on September 1, 2020.
Upregulated galectin-1 in Angiostrongylus cantonensis L5 reduces body fat and increases oxidative stress tolerance
Authors: Sun Wei-Wei , Yan Xiu-Mei , Qiao Ai-Jun , Zhang Yuan-Jiao , Yang Ling , Huang Hui-Cong , Shi Hong-Fei , Yan Bao-Long
Published: February 2022

Background

Angiostrongylus cantonensis L5, parasitizing human cerebrospinal fluid, causes eosinophilic meningitis, which is attributed to tissue inflammatory responses caused primarily by the high percentage of eosinophils. Eosinophils are also involved in killing helminths, using the peroxidative oxidation and hydrogen peroxide (H2O2) generated by dismutation of superoxide produced during respiratory burst. In contrast, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival. In previous study, we demonstrated the extracellular function of Acan-Gal-1 in inducing the apoptosis of macrophages. Here, the intracellular functions of Acan-Gal-1 were investigated, aiming to further reveal the mechanism involved in A. cantonensis L5 worms surviving inflammatory responses in the human central nervous system.

Methods

In this study, a model organism, Caenorhabditis elegans, was used as a surrogate to investigate the intracellular functions of Acan-Gal-1 in protecting the worm from its host’s immune attacks. First, structural characterization of Acan-Gal-1 was analyzed using bioinformatics; second, qRT-PCR was used to monitor the stage specificity of Acan-gal-1 expression in A. cantonensis. Microinjections were performed to detect the tissue specificity of lec-1 expression, the homolog of Acan-gal-1 in C. elegans. Third, microinjection was performed to develop Acan-gal-1::rfp transgenic worms. Then, oxidative stress assay and Oil Red O fat staining were used to determine the functions of Acan-Gal-1 in C. elegans.

Results

The results of detecting the stage specificity of Acan-gal-1 expression showed that Acan-Gal-1 was upregulated in both L5 and adult worms. Detection of the tissue specificity showed that the homolog of Acan-gal-1 in C. elegans, lec-1 was expressed ubiquitously and mainly localized in cuticle. Investigating the intracellular functions of Acan-Gal-1 in the surrogate C. elegans showed that N2 worms expressing pCe-lec-1::Acan-gal-1::rfp, with lipid deposition reduced, were significantly resistant to oxidative stress; lec-1 mutant worms, where lipid deposition increased, showed susceptible to oxidative stress, and this phenotype could be rescued by expressing pCe-lec-1::Acan-gal-1::rfp. Expressing pCe-lec-1::Acan-gal-1::rfp or lec-1 RNAi in fat-6;fat-7 double-mutant worms, where fat stores were reduced, had no significant effect on the oxidative stress tolerance.

Conclusion

In C. elegans worms, upregulated Acan-Gal-1 plays a defensive role against damage due to oxidative stress for worm survival by reducing fat deposition. This might indicate the mechanism by which A. cantonensis L5 worms, with upregulated Acan-Gal-1, survive the immune attack of eosinophils in the human central nervous system.

Graphical Abstract
Double burden of COVID-19 knowledge deficit: low health literacy and high information avoidance
Authors: Chen Xuewei , Li Ming , Kreps Gary L.
Published: February 2022

Objective

People with lower levels of health literacy are likely to report engaging in information avoidance. However, health information avoidance has been overlooked in previous research on responses to viral outbreaks. The purpose of this cross-sectional survey study was to assess the relationship between health literacy and COVID-19 information avoidance. Students (n = 561) at a university in the south central region of the U.S. completed our online survey conducted from April to June 2020 using simple random sampling. We measured information avoidance and the degree to which people opt not to learn about COVID-19 when given the choice. We assessed participants’ health literacy level using the Newest Vital Sign (NVS), eHealth Literacy Scale (eHEALS), and All Aspect of Health Literacy Scale (AAHLS).

Results

Those with lower health literacy were more likely to avoid information about COVID-19. This negative association between health literacy and information avoidance was consistent across all types of health literacy measures: NVS scores (b = − 0.47, p = 0.033), eHEALS scores (b = − 0.12, p = 0.003), functional health literacy (b = − 0.66, p = 0.001), communicative health literacy (b = − 0.94, p < 0.001), information appraisal (b = − 0.36, p = 0.004), and empowerment (b = − 0.62, p = 0.027). The double burden of low health literacy and high information avoidance is likely to lead to a lack of knowledge about COVID-19.
Altered central and blood glutathione in Alzheimer’s disease and mild cognitive impairment: a meta-analysis
Authors: Chen Jinghan Jenny , Thiyagarajah Mathura , Song Jianmeng , Chen Clara , Herrmann Nathan , Gallagher Damien , Rapoport Mark J. , Black Sandra E. , Ramirez Joel , Andreazza Ana C. , Oh Paul , Marzolini Susan , Graham Simon J. , Lanctôt Krista L.
Published: February 2022

Background

Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease.

Aim

To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses.

Method

Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947–June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively.

Results

For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] −1.45 [−1.83, −1.06], p<0.001) and MCI (−1.15 [−1.71, −0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (−0.87 [−1. 30, −0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (−0.66 [−1.11, −0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.

Conclusion

Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.
A review on advances in 18F-FDG PET/CT radiomics standardisation and application in lung disease management
Authors: Anan Noushin , Zainon Rafidah , Tamal Mahbubunnabi
Published: February 2022

Radiomics analysis quantifies the interpolation of multiple and invisible molecular features present in diagnostic and therapeutic images. Implementation of 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics captures various disorders in non-invasive and high-throughput manner.18F-FDG PET/CT accurately identifies the metabolic and anatomical changes during cancer progression. Therefore, the application of18F-FDG PET/CT in the field of oncology is well established. Clinical application of18F-FDG PET/CT radiomics in lung infection and inflammation is also an emerging field. Combination of bioinformatics approaches or textual analysis allows radiomics to extract additional information to predict cell biology at the micro-level. However, radiomics texture analysis is affected by several factors associated with image acquisition and processing. At present, researchers are working on mitigating these interrupters and developing standardised workflow for texture biomarker establishment. This review article focuses on the application of18F-FDG PET/CT in detecting lung diseases specifically on cancer, infection and inflammation. An overview of different approaches and challenges encountered on standardisation of18F-FDG PET/CT technique has also been highlighted. The review article provides insights about radiomics standardisation and application of18F-FDG PET/CT in lung disease management.
Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells
Authors: Jiang Jianan , Qin Jinhua , Li Jisheng , Lin Xiaosong , Zhang Bowen , Fan Zeng , He Lijuan , Zeng Quan , Yue Wen , Zheng Min , Pei Xuetao , Li Yanhua
Published: February 2022

Background

Ex vivo production of induced megakaryocytes (MKs) and platelets from stem cells is an alternative approach for supplying transfusible platelets. However, it is difficult to generate large numbers of MKs and platelets from hematopoietic stem cells and progenitor cells (HSPCs).

Methods

To optimize the differentiation efficiency of megakaryocytic cells from HSPCs, we first employed a platelet factor 4 (PF4)-promoter reporter and high-throughput screening strategy to screen for small molecules. We also investigated the effects and possible mechanisms of candidate small molecules on megakaryocytic differentiation of human HSPCs.

Results

The small molecule Ricolinostat remarkably promoted the expression of PF4-promoter reporter in the megakaryocytic cell line. Notably, Ricolinostat significantly enhanced the cell fate commitment of MK progenitors (MkPs) from cord blood HSPCs and promoted the proliferation of MkPs based on cell surface marker detection, colony-forming unit-MK assay, and quantitative real-time PCR analyses. MkPs generated from Ricolinostat-induced HSPCs differentiated into mature MKs and platelets. Mechanistically, we found that Ricolinostat enhanced MkP fate mainly by inhibiting the secretion of IL-8 and decreasing the expression of the IL-8 receptor CXCR2.

Conclusion

The addition of Ricolinostat to the culture medium promoted MkP differentiation from HSPCs and enhanced the proliferation of MkPs mainly by suppressing the IL-8/CXCR2 pathway. Our results can help the development of manufacturing protocols for the efficient generation of MKs and platelets from stem cells in vitro.
Single-cell analysis of mouse uterus at the invasion phase of embryo implantation
Authors: He Jia-Peng , Tian Qing , Zhu Qiu-Yang , Liu Ji-Long
Published: February 2022

Background

Embryo implantation into the uterus is a crucial step for human reproduction. A hypothesis has been proposed that the molecular circuit invented by trophoblasts for invasive embryo implantation during evolution might be misused by cancer cells to promote malignancy. Unfortunately, our current understanding of the molecular mechanism underlying embryo implantation is far from complete.

Results

Here we used the mouse as an animal model and generated a single-cell transcriptomic atlas of the embryo implantation site of mouse uterus at the invasion phase of embryo implantation on gestational day 6. We revealed 23 distinct cell clusters, including 5 stromal cell clusters, 2 epithelial cell clusters, 1 smooth muscle cell cluster, 2 pericyte clusters, 4 endothelial cell clusters, and 9 immune cell clusters. Through data analysis, we identified differentially expression changes in all uterine cell types upon embryo implantation. By integrated with single-cell RNA-seq data from E5.5 embryos, we predicted cell–cell crosstalk between trophoblasts and uterine cell types.

Conclusions

Our study provides a valuable resource for understanding of the molecular mechanism of embryo implantation.
RPCA-DRNN technique for monaural singing voice separation
Authors: Lai Wen-Hsing , Wang Siou-Lin
Published: February 2022

In this study, we propose a methodology for separating a singing voice from musical accompaniment in a monaural musical mixture. The proposed method uses robust principal component analysis (RPCA), followed by postprocessing, including median filter, morphology, and high-pass filter, to decompose the mixture. Subsequently, a deep recurrent neural network comprising two jointly optimized parallel-stacked recurrent neural networks (sRNNs) with mask layers and trained on limited data and computation is applied to the decomposed components to optimize the final estimated separated singing voice and background music to further correct misclassified or residual singing and background music in the initial separation. The experimental results of MIR-1K, ccMixter, and MUSDB18 datasets and the comparison with ten existing techniques indicate that the proposed method achieves competitive performance in monaural singing voice separation. On MUSDB18, the proposed method reaches the comparable separation quality in less training data and lower computational cost compared to the other state-of-the-art technique.
Under detection of depression in primary care settings in low and middle-income countries: a systematic review and meta-analysis
Authors: Fekadu Abebaw , Demissie Mekdes , Birhane Rahel , Medhin Girmay , Bitew Tesera , Hailemariam Maji , Minaye Abebaw , Habtamu Kassahun , Milkias Barkot , Petersen Inge , Patel Vikram , Cleare Anthony J. , Mayston Rosie , Thornicroft Graham , Alem Atalay , Hanlon Charlotte , Prince Martin
Published: February 2022

Background

Depression is one of the commonest mental disorders in primary care but is poorly identified. The objective of this review was to determine the level of detection of depression by primary care clinicians and its determinants in studies from low- to middle-income countries (LMICs).

Methods

A systematic review and meta-analysis was conducted using PubMed, PsycINFO, MEDLINE, EMBASE, LILAC, and AJOL with no restriction of year of publication. Risk of bias within studies was evaluated with the Effective Public Health Practice Project (EPHPP). “Gold standard” diagnosis for the purposes of this review was based on the 9-item Patient Health Questionnaire (PHQ-9; cutoff scores of 5 and 10), other standard questionnaires and interview scales or expert diagnosis. Meta-analysis was conducted excluding studies on special populations. Analyses of pooled data were stratified by diagnostic approaches.

Results

A total of 3159 non-duplicate publications were screened. Nine publications, 2 multi-country studies, and 7 single-country studies, making 12 country-level reports, were included. Overall methodological quality of the studies was good. Depression detection was 0.0% in four of the twelve reports and < 12% in another five. PHQ-9 was the main tool used: the pooled detection in two reports that used PHQ-9 at a cutoff point of 5 (combined sample size = 1426) was 3.9% (95% CI = 2.3%, 5.5%); in four reports that used PHQ-9 cutoff score of 10 (combined sample size = 5481), the pooled detection was 7.0% (95% CI = 3.9%, 10.2%). Severity of depression and suicidality were significantly associated with detection.

Conclusions

While the use of screening tools is an important limitation, the extremely low detection of depression by primary care clinicians poses a serious threat to scaling up mental healthcare in LMICs. Interventions to improve detection should be prioritized.

Systematic review registration

PROSPERO CRD42016039704.
Tuberculosis poor treatment outcomes and its determinants in Kilifi County, Kenya: a retrospective cohort study from 2012 to 2019
Authors: Katana Geoffrey G. , Ngari Moses , Maina Teresia , Sanga Deche , Abdullahi Osman A.
Published: February 2022

Background

Tuberculosis (TB) is one of the leading causes of deaths in Africa, monitoring its treatment outcome is essential to evaluate treatment effectiveness. The study aimed to evaluate proportion of poor TB treatment outcomes (PTO) and its determinants during six-months of treatment at Kilifi County, Kenya.

Methods

We conducted a retrospective analysis of data from the TB surveillance system (TIBU) in Kilifi County, Kenya from 2012 to 2019. The outcome of interest was PTO (lost-to-follow-up (LTFU), death, transferred out, treatment failure, drug resistance) or successful treatment (cured or completed treatment). We performed time-stratified (at three months follow-up) survival regression analyses accounting for sub-county heterogeneity to determine factors associated with PTO.

Results

We included 14,706 TB patients, their median (IQR) age was 37
(28–50) years and 8,791 (60%) were males. A total of 13,389 (91%) were on first line anti-TB treatment (2RHZE/4RH), 4,242 (29%) were HIV infected and 192 (1.3%) had other underlying medical conditions. During 78,882 person-months of follow-up, 2,408 (16%) patients had PTO: 1,074 (7.3%) deaths, 776 (5.3%) LTFU, 415 (2.8%) transferred out, 103 (0.7%) treatment failure and 30 (0.2%) multidrug resistance. The proportion of poor outcome increased from 7.9% in 2012 peaking at 2018 (22.8%) and slightly declining to 20% in 2019 (trend test P = 0.03). Over two-thirds 1,734 (72%) poor outcomes occurred within first three months of follow-up. In the first three months of TB treatment, overweight ((aHR 0.85 (95%CI 0.73–0.98), HIV infected not on ARVS (aHR 1.72 (95% CI 1.28–2.30)) and year of starting treatment were associated with PTO. However, in the last three months of treatment, elderly age ≥50 years (aHR 1.26 (95%CI 1.02–1.55), a retreatment patient (aHR 1.57 (95%CI 1.28–1.93), HIV infected not on ARVs (aHR 2.56 (95%CI 1.39–4.72), other underlying medical conditions (aHR 2.24 (95%CI 1.41–3.54)) and year of starting treatment were positively associated with PTO while being a female (aHR 0.83 (95%CI 0.70–0.97)) was negatively associated with PTO.

Conclusions

Over two-thirds of poor outcomes occur in the first three months of TB treatment, therefore greater efforts are needed during this phase. Interventions targeting HIV infected and other underlying medical conditions, the elderly and retreated patients provide an opportunity to improve TB treatment outcome.
Performance determinants of unsupervised clustering methods for microbiome data
Authors: Shi Yushu , Zhang Liangliang , Peterson Christine B. , Do Kim-Anh , Jenq Robert R.
Published: February 2022

Background

In microbiome data analysis, unsupervised clustering is often used to identify naturally occurring clusters, which can then be assessed for associations with characteristics of interest. In this work, we systematically compared beta diversity and clustering methods commonly used in microbiome analyses. We applied these to four published datasets where highly distinct microbiome profiles could be seen between sample groups, as well a clinical dataset with less clear separation between groups.

Results

Although no single method outperformed the others consistently, we did identify the key scenarios where certain methods can underperform. Specifically, the Bray Curtis (BC) metric resulted in poor clustering in a dataset where high-abundance OTUs were relatively rare. In contrast, the unweighted UniFrac (UU) metric clustered poorly on dataset with a high prevalence of low-abundance OTUs. To explore these hypotheses about BC and UU, we systematically modified the properties of the poorly performing datasets and found that this approach resulted in improved BC and UU performance. Based on these observations, we rationally combined BC and UU to generate a novel metric. We tested its performance while varying the relative contributions of each metric and also compared it with another combined metric, the generalized UniFrac distance. The proposed metric showed high performance across all datasets.

Conclusions

Our systematic evaluation of clustering performance in these five datasets demonstrates that there is no existing clustering method that universally performs best across all datasets. We propose a combined metric of BC and UU that capitalizes on the complementary strengths of the two metrics.
Frequencies of CYP2D6 genetic polymorphisms in Arab populations
Authors: Alali Mousa , Ismail Al-khalil Wouroud , Rijjal Sara , Al-Salhi Lana , Saifo Maher , Youssef Lama A.
Published: February 2022

CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevantCYP2D6alleles in the Arabs countries. Articles published before May 2021 that reportedCYP2D6genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. ActiveCYP2D6gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function alleleCYP2D6*4ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-functionCYP2D6*10allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function alleleCYP2D6*41was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity ofCYP2D6alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine theirCYP2D6allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.