bluuebunny/crossref_metadata_2025 huggingface dataset:
Large lateral tibial slope and lateral-to-medial slope difference are risk factors for poorer clinical outcomes after posterolateral meniscus root tear repair in anterior cruciate ligament reconstruction
Authors: Wong Cham Kit , Man Gene Chi Wai , He Xin , Ng Jonathan Patrick , Ng Alex Wing Hung , Ong Michael Tim Yun , Yung Patrick Shu Hang
Published: March 2022

Background

Meniscus root tear is an uncommon but detrimental injury of the knee. Hoop stress is lost during meniscus root tear, which can lead to excessive tibiofemoral contact pressure and early development of osteoarthritis. Posterolateral meniscus root tears (PLRT) are more commonly associated with anterior cruciate ligament (ACL) tears. As the lateral compartment is less congruent than the medial compartment, it is more susceptible to a shearing force, which is increased in the ACL-deficient knee. In accordance with the compressive axial load, the increase in the tibial slope would generate a greater shearing force. The additional lateral compartment mobility caused by ACL tear should be reduced after ACL reconstruction (ACLR). However, there is a lack of evidence to conclude that ACLR can sufficiently limit the effect of large tibial slope (LTS) on the healing after PLRT repair. This study aimed to evaluate whether a steep LTS would be a risk factor for poorer clinical outcomes after PLRT repair concomitant with ACLR.

Methods

In this retrospective study, a chart review was conducted to identify patients with concomitant unilateral primary ACLR and PLRT repair. Patients with a partial tear or healed tear were excluded. Postoperative MRI and clinical assessments were performed at a mean follow up of 35 months. MRI data was used to measure the LTS, medial tibial slope (MTS), coronal tibial slope (CTS), the lateral-to-medial slope difference (LTS-MTS) and meniscus healing and extrusion. Functional outcomes were evaluated by patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm and Tegner scores) and KT-1000 arthrometer assessment. Interobserver reproducibility was assessed by two reviewers.

Results

Twenty-five patients were identified for the analysis. Patients with larger LTS and larger LTS-MTS differences were shown to be correlated with poorer IKDC scores after surgery (R = -0.472, p = 0.017 and R = -0.429, p = 0.032, respectively). Herein, patients with LTS ≥ 6° or LTS-MTS ≥ 3° demonstrated poorer IKDC scores.

Conclusion

A large LTS (≥ 6°) and a large difference of LTS-MTS (≥ 3°) were shown to be risk factors for poorer functional and radiological outcomes for PLRT repair in patients after ACLR. Clinically, closer monitoring and a more stringent rehabilitation plan for patients with LTS ≥ 6° or LTS-MTS ≥ 3° would be recommended.
Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss
Authors: Pouwels Sjaak , Sakran Nasser , Graham Yitka , Leal Angela , Pintar Tadeja , Yang Wah , Kassir Radwan , Singhal Rishi , Mahawar Kamal , Ramnarain Dharmanand
Published: March 2022

Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.

In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.
Magnitude and associated factors of early Implanon discontinuation among rural women in public health facilities of central Ethiopia: a community-based cross-sectional study
Authors: Obsu Mekonnen , Hundessa Berecha , Garoma Sileshi , Aman Haji , Merga Hailu
Published: March 2022

Background

Advocating for and promoting contraception use is critical in reducing mother and child morbidity and mortality. Early Implanon discontinuation may result in unwanted pregnancies and induced abortions. Although there has been research in Ethiopia on long-acting reversible contraceptives, there has been none on early Implanon removal among rural women who have used and removed it. Hence, this study aimed to investigate the magnitude of Implanon discontinuation and related characteristics among women who had the Implanon removed in central Ethiopian public health facilities.

Methods

A community-based cross-sectional study was conducted among all women of the reproductive age group who had removed Implanon after using it. A simple random sampling technique was used to select 373 women after proportional allocation to each health facility. Data were collected using a pretested semi-structured interviewer-administered questionnaire adapted from previous studies. Data were entered using EpiInfo and exported to SPSS version 21 for analysis. A binary logistic regression model was used to determine the association between the outcome variable and independent variables. A p-value less than 0.25 was used as a cutoff point to select candidate variables for the final model. Then, a p value less than 0.05, AOR, and a 95% confidence level were used to declare statistical significance.

Result

A total of 360 participants responded to the questionnaires, making a response rate of 96.5%. In this study, the early discontinuation rate was 42% (95% CI 36.9–47.7). No formal education (AOR = 0.53 [95% CI 0.3–0.94], having medium monthly income (AOR = 3.02 [95% CI 1.38–6.6]), inadequate pre-insertion counseling (AOR = 0.55 [95% CI 0.31–0.98]), lack of appointment for follow up (AOR = 0.16 [95% CI 0.05–0.54]), didn`t satisfy with service provided (AOR = 0.067 [95% CI 0.015–0.29] and developed side effect (AOR) = 4.45 [95% CI 2.37–8.36] were significantly associated with Implanon discontinuation.

Conclusion

The discontinuation rate of Implanon among those who removed it after using it in this study was high. Lack of formal education, having a medium-income, inadequate pre-insertion counseling, lack of appointments for the follow-up, poor satisfaction, and problems with side effects were the factors associated with early discontinuation rate. Hence, quality family planning service provision is essential to reduce the discontinuation rate.
‘Joining a group was inspiring’: a qualitative study of service users’ experiences of yoga on social prescription
Authors: Cheshire Anna , Richards Rebecca , Cartwright Tina
Published: March 2022

Background

Yoga is becoming an increasingly popular holistic approach in the West to manage long-term health conditions. This study presents the evaluation of a pilot yoga intervention, Yoga4Health, that was developed for the NHS to be socially prescribed to patients at risk of developing specific health conditions (risk factors for cardiovascular disease, pre-diabetes, anxiety/depression or experiencing social isolation). The aim of this qualitative study was to explore service users’ experiences of Yoga4Health and the acceptability of the programme.

Methods

Qualitative data were collected from three sources: 1. Open-ended questions on questionnaires completed by services users at three different time-points (baseline, post intervention and 3 months); 2. Interviews and focus groups with a subset of participants (n = 22); 3. interviews with yoga teachers delivering Yoga4Health (n = 7). Each data source was analysed thematically, then findings were combined.

Results

Of participants completing baseline questionnaires (n = 240), 82.5% were female, 50% White, with a mean age of 53 (range 23–82) years. Baseline questionnaires revealed key motivations to attend Yoga4Health were to improve psychological and physical health, and believing Yoga4Health would be accessible for people with their health condition. Post-intervention, participants reported a range of benefits across psychological, physical and social domains from Yoga4Health. Increased confidence in self-management of health was also reported, and a number of participants described making positive lifestyle changes after attending the programme. Unanticipated benefits of yoga emerged for participants, such as enjoyment and social connectedness, which facilitated ongoing attendance and practice. Also key to facilitating practice (during and after the intervention) were suitability of the classes for those with health conditions, practising with a group and qualities of the yoga teacher. Home practice was supported by course materials (manual, videos), as well as the teaching of techniques for everyday application that offered immediate benefits, such as breathing practices. Follow-up questionnaires revealed a key challenge was continuation of practice once the intervention had finished, with the structure of a class important in supporting practice.

Conclusions

Yoga4Health was a highly acceptable intervention to services users, which brought a range of biopsychosocial improvements, suggesting yoga is an appropriate intervention to offer on social prescription.
Clinical preceptorship in Ghana in the era of COVID-19 pandemic: an interventional study
Authors: Enyan Nancy Innocentia Ebu , Boso Christian Makafui , Ofori Anastasia Adomah , Agyare Dorcas Frempomaa , Aboh Irene Korkoi , Dike Nkechi Oluwakemi , Agyei Douglas Darko , Obiri-Yeboah Dorcas
Published: March 2022

Background

Innovations in clinical nursing education are critical in enhancing the experiences of students, especially in the era of coronavirus pandemic. This study aimed at investigating nurse preceptors’ perceptions of use, intention to use and self-efficacy towards digital technology in preceptorship in the Cape Coast Metropolis of Ghana.

Methods

A concurrent type of mixed-methods design with a non-randomised interventional study using three-phase multi-methods technique was conducted among nurse preceptors in the Cape Coast Metropolis in the Central Region of Ghana. Forty-five nurse preceptors participated in a pre and post training intervention while seven were purposively selected for the qualitative interview. Complimentarity method of triangulation was used in the analysis. The quantitative data were analysed with STATA version 16 and presented using frequencies, percentages, means with standard deviations and McNemar's test while qualitative data were analysed using the six steps approach to qualitative data analysis by Braun and Clarke.

Results

Perceived usefulness statement “using technology will improve clinical teaching” increased from 19 (42.22%) at baseline to 44 (97.78%) post intervention. Perceived ease of using technology statement “I would find it easy to get this technology to do what I want it to do” also increased from 36 (80.00%) to 41 (91.11%) post intervention. Self-efficacy increased from 40 (88.89%) to 43 (95.56%) after the intervention. There was a statistically significant difference between pre-training and post-training scores regarding tablet (p = 0.016) and experience with online library resources (p = 0.039). The qualitative results yielded three themes, namely: strengths of using technology; constraints in the learning environment; and future of technological approach to clinical teaching.

Conclusions

The training intervention improved participants intentions, self-efficacy, perceived use and perceived ease of use of technology. However, there are constraints in the clinical learning environment including students and preceptor-related factors, and institutional factors that needs to be addressed as part of efforts to implement technology in clinical teaching in this era of COVID-19 pandemic and beyond.
Explaining the consequences of missed nursing care from the perspective of nurses: a qualitative descriptive study in Iran
Authors: Janatolmakan Maryam , Khatony Alireza
Published: March 2022

Background

Missed nursing care is a global challenge that can have many consequences. Knowing the experiences of clinical nurses can be helpful. Therefore, this study was conducted to explain the experiences of Iranian nurses regarding the consequences of missed nursing care.

Methods

This qualitative descriptive study was conducted with a content analysis approach. Sampling was done by the purposeful sampling method and continued until data saturation. Data were collected by in-depth semi-structured interviews. Data were analyzed using qualitative content analysis and Graneheim and Lundman’s method. MAXQDA version 10 software was used for data management.

Results

The participants included 14 nurses with a mean age of 38.7 ± 7.7 years. The data were classified into three categories: patient-related outcomes, nurse-related outcomes, and organization-related outcomes. These categories included nine subcategories entitled "moral distress", "job dissatisfaction", " decreased quality of nursing care "," patient dissatisfaction ","adverse events"," absenteeism ","intention to leave and subsequent turnover", "decreased hospital credit", and "increased hospital costs".

Conclusion

Missed nursing care can have adverse consequences for the patients, nurses, and organizations. Therefore, it is necessary to adopt management strategies such as providing sufficient manpower and increasing nurses' job satisfaction to reduce the amount of missed nursing care. Further studies are needed to explain the predictors of the missed nursing care consequences.
Analysis of echolocation behavior of bats in “echo space” using acoustic simulation
Authors: Teshima Yu , Yamada Yasufumi , Tsuchiya Takao , Heim Olga , Hiryu Shizuko
Published: March 2022

Background

Echolocating bats use echo information to perceive space, control their behavior, and adjust flight navigation strategies in various environments. However, the echolocation behavior of bats, including echo information, has not been thoroughly investigated as it is technically difficult to measure all the echoes that reach the bats during flight, even with the conventional telemetry microphones currently in use. Therefore, we attempted to reproduce the echoes received at the location of bats during flight by combining acoustic simulation and behavioral experiments with acoustic measurements. By using acoustic simulation, echoes can be reproduced as temporal waveforms (including diffracted waves and multiple reflections), and detailed echo analysis is possible even in complex obstacle environments.

Results

We visualized the spatiotemporal changes in the echo incidence points detected by bats during flight, which enabled us to investigate the “echo space” revealed through echolocation for the first time. We then hypothesized that by observing the differences in the “echo space” before and after spatial learning, the bats’ attentional position would change. To test this hypothesis, we examined how the distribution of visualized echoes concentrated at the obstacle edges after the bats became more familiar with their environment. The echo incidence points appeared near the edge even when the pulse direction was not toward the edge. Furthermore, it was found that the echo direction correlated with the turn rate of the bat’s flight path, revealing for the first time the relationship between the echo direction and the bat’s flight path.

Conclusions

We were able to clarify for the first time how echoes space affects echolocation behavior in bats by combining acoustic simulations and behavioral experiments.
Diagnostic performance of RT-PCR-based sample pooling strategy for the detection of SARS-CoV-2
Authors: Hueda-Zavaleta Miguel , Copaja-Corzo Cesar , Benites-Zapata Vicente A. , Cardenas-Rueda Pedro , Maguiña Jorge L. , Rodríguez-Morales Alfonso J.
Published: March 2022

Background

The rapid spread of SARS-CoV-2 has created a shortage of supplies of reagents for its detection throughout the world, especially in Latin America. The pooling of samples consists of combining individual patient samples in a block and analyzing the group as a particular sample. This strategy has been shown to reduce the burden of laboratory material and logistical resources by up to 80%. Therefore, we aimed to evaluate the diagnostic performance of the pool of samples analyzed by RT-PCR to detect SARS-CoV-2.

Methods

A cross-sectional study of diagnostic tests was carried out. We individually evaluated 420 samples, and 42 clusters were formed, each one with ten samples. These clusters could contain 0, 1 or 2 positive samples to simulate a positivity of 0, 10 and 20%, respectively. RT-PCR analyzed the groups for the detection of SARS-CoV-2. The area under the ROC curve (AUC), the Youden index, the global and subgroup sensitivity and specificity were calculated according to their Ct values that were classified as high (H: ≤ 25), moderate (M: 26–30) and low (L: 31–35) concentration of viral RNA.

Results

From a total of 42 pools, 41 (97.6%) obtained the same result as the samples they contained (positive or negative). The AUC for pooling, Youden index, sensitivity, and specificity were 0.98 (95% CI, 0.95–1); 0.97 (95% CI, 0.90–1.03); 96.67% (95% CI; 88.58–100%) and 100% (95% CI; 95.83–100%) respectively. In the stratified analysis of the pools containing samples with Ct ≤ 25, the sensitivity was 100% (95% CI; 90–100%), while with the pools containing samples with Ct ≥ 31, the sensitivity was 80% (95% CI, 34.94–100%). Finally, a higher median was observed in the Ct of the clusters, with respect to the individual samples (p < 0.001).

Conclusions

The strategy of pooling nasopharyngeal swab samples for analysis by SARS-CoV-2 RT-PCR showed high diagnostic performance.
PSMC2 is overexpressed in glioma and promotes proliferation and anti-apoptosis of glioma cells
Authors: Zheng Xiaoyang , Wang Yuguang , Wang Dongxu , Wan Jingru , Qin Xiangying , Mu Zhuang , Hu Nan
Published: March 2022

Background

This study aims to investigate the effect of PSMC2 expression on the clinical prognosis of glioma patients and its molecular mechanism.

Methods

TCGA multi-tumor screening and survival analysis were combined to explore the differential expression of PSMC2 in multi-tumor. PSMC2 expression in glioma and normal tissues was detected by Western blot and RT-qPCR. Kaplan-Meier survival curve was used to visualize the effect of PSMC2 expression on the overall survival rate and disease-free survival rate of patients with glioma. The highly expressed cell line U343MG was selected to construct a PSMC2 knockdown model by siRNA transfection, and the effect of PSMC2 knockdown on cell proliferation ability was evaluated by CCK-8 assay. Gene-set enrichment analysis of PSMC2 co-expression genes was carried out to predict the molecular mechanism of their regulation of tumor cell phenotypes, and the analysis results were verified by flow cytometry and Western blot.

Results

Through broad-spectrum screening of 31 kinds of tumors, we found that PSMC2 was upregulated in most tumors, but PSMC2 was most significantly overexpressed in gliomas and correlated with poor prognosis in glioma patients. The results of Western blot and qRT-PCR showed that PSMC2 was significantly overexpressed in glioma tissues. Further survival analysis revealed that the overall survival and disease-free survival of patients with low PSMC2 expression were significantly better than that of patients with high PSMC2 expression. The proliferation of U343MG cells was significantly inhibited after PSMC2 knockdown. Enrichment analysis of PSMC2 co-expression genes indicated that PSMC2 affected the apoptosis process. The expression of apoptosis-related proteins also significantly changed following PSMC2 knockdown.

Conclusions

PSMC2 promotes the proliferation of glioma cells and inhibits the apoptosis, which is expected to be a potential therapeutic target for glioma.
Circulating brain-derived neurotrophic factor as a potential biomarker in stroke: a systematic review and meta-analysis
Authors: Mojtabavi Helia , Shaka Zoha , Momtazmanesh Sara , Ajdari Atra , Rezaei Nima
Published: March 2022

Background

Stroke, an acute cerebrovascular event, is a leading cause of disability, placing a significant psycho-socioeconomic burden worldwide. The adaptation and reorganization process following any neuronal damage is regarded as neuroplasticity. Among many factors believed to attribute to this process, Brain-derived Neurotrophic Factor (BDNF) is a neurotrophin coordinating neuroplasticity after various neurological disorders such as stroke.

Methods

We conducted a systematic search in the main electronic medical databases in January 2021. Primarily we want to compare BDNF levels between patients with stroke and healthy controls (HC). Additional aims included investigation of (1) longitudinal changes in the BDNF levels post-stroke, (2) effects of physical training, (3) repeated transcranial magnetic stimulation (rTMS), and presence of depression on BDNF levels in patients with stroke.

Results

Among 6243 reviewed records from PubMed, Web of Science, and Scopus, 62 studies were eligible for inclusion in our systematic review. Subjects with stroke, n = 1856, showed lower BDNF levels compared to HC, n = 1191 (SMD [95%CI] = − 1.04 [− 1.49 to − 0.58]). No significant difference was detected in the level of BDNF through time points past stroke. BDNF levels were lower in the patients with depression compared to non-depressed subjects (SMD [95%CI] = − 0.60 [− 1.10 to − 0.10]). Physical training had an immediate positive effect on the BDNF levels and not statistically significant effect in the long term; SMD [95%CI] = 0.49 [0.09 to 0.88]) and SMD [95%CI] = 0.02 [− 0.43 to 0.47]). Lastly, rTMS showed no effect on the level of BDNF with 0.00 SMD.

Conclusions

Our study confirms that stroke significantly decreases the level of BDNF in various domains such as cognition, affect, and motor function. As BDNF is the major representative of neuroplasticity within nervous system, it is believed that stroke has a significant impact on the CNS regeneration, which is permanent if left untreated. This effect is intensified with coexisting conditions such as depression which further decrease the BDNF level but the net impact yet needs to be discovered. We also conclude that exercise and some interventions such as different medications could effectively reverse the damage but further studies are crucial to reach the exact modality and dosage for their optimal effect.
Two for one: targeting BCMA and CD19 in B-cell malignancies with off-the-shelf dual-CAR NK-92 cells
Authors: Roex Gils , Campillo-Davo Diana , Flumens Donovan , Shaw Philip Anthony Gilbert , Krekelbergh Laurens , De Reu Hans , Berneman Zwi N. , Lion Eva , Anguille Sébastien
Published: March 2022

Background

Chimeric antigen receptor (CAR) T-cell therapy has proven to be a valuable new treatment option for patients with B-cell malignancies. However, by applying selective pressure, outgrowth of antigen-negative tumor cells can occur, eventually resulting in relapse. Subsequent rescue by administration of CAR-T cells with different antigen-specificity indicates that those tumor cells are still sensitive to CAR-T treatment and points towards a multi-target strategy. Due to their natural tumor sensitivity and highly cytotoxic nature, natural killer (NK) cells are a compelling alternative to T cells, especially considering the availability of an off-the-shelf unlimited supply in the form of the clinically validated NK-92 cell line.

Methods

Given our goal to develop a flexible system whereby the CAR expression repertoire of the effector cells can be rapidly adapted to the changing antigen expression profile of the target cells, electrotransfection with CD19-/BCMA-CAR mRNA was chosen as CAR loading method in this study. We evaluated the functionality of mRNA-engineered dual-CAR NK-92 against tumor B-cell lines and primary patient samples. In order to test the clinical applicability of the proposed cell therapy product, the effect of irradiation on the proliferative rate and functionality of dual-CAR NK-92 cells was investigated.

Results

Co-electroporation of CD19 and BMCA CAR mRNA was highly efficient, resulting in 88.1% dual-CAR NK-92 cells. In terms of CD107a degranulation, and secretion of interferon (IFN)-γ and granzyme B, dual-CAR NK-92 significantly outperformed single-CAR NK-92. More importantly, the killing capacity of dual-CAR NK-92 exceeded 60% of single and dual antigen-expressing cell lines, as well as primary tumor cells, in a 4h co-culture assay at low effector to target ratios, matching that of single-CAR counterparts. Furthermore, our results confirm that dual-CAR NK-92 irradiated with 10 Gy cease to proliferate and are gradually cleared while maintaining their killing capacity.

Conclusions

Here, using the clinically validated NK-92 cell line as a therapeutic cell source, we established a readily accessible and flexible platform for the generation of highly functional dual-targeted CAR-NK cells.
Differences in addiction and recovery gains according to gender – gender barriers and specific differences in overall strengths growth
Authors: Abreu Minero Valeria , Best David , Brown Lorna , Patton David , Vanderplasschen Wouter
Published: March 2022

Background

There is growing evidence on the importance of a gendered understanding of recovery. Gender differences have been reported in relation to the nature and extent of substance use, pathways to and through substance use disorder and recovery capital acquisition and maintenance. There is little existing research on factors associated with recovery capital growth by gender.

Methods

The current paper uses the European Life in Recovery database to assess specific domains of the Strengths and Barriers Recovery Scale (SABRS) that best predict growth of recovery capital amongst people in recovery from drug addiction. The 1313 participants were drawn from the REC-PATH study and recruited by the Recovery Users Network (RUN) from across Europe. Bivariate and multivariate analyses were performed to identify relationships between specific SABRS items and gender, as well as differences in the dimensions of the SABRS scale most likely to predict recovery capital growth by gender.

Results

Between their time in active addiction and in recovery, females show greater growth in strengths, despite females reporting fewer recovery strengths during active addiction than males, and males have greater reductions in barriers to recovery compared to females. Multivariate analyses show that strengths specifically related to prosocial meaningful activities are found to be highly significant for growth of recovery capital amongst males, whereas strengths related to both prosocial meaningful activities and general health management seem particularly relevant for growth of recovery capital amongst females.

Conclusions

We conclude that this further demonstration of gender differences in recovery pathways should suggest gender-specific approaches adopted in recovery community organisations to address these different needs.
Macropinocytosis is an alternative pathway of cysteine acquisition and mitigates sorafenib-induced ferroptosis in hepatocellular carcinoma
Authors: Byun Jun-Kyu , Lee Seunghyeong , Kang Gil Won , Lee Yu Rim , Park Soo Young , Song Im-Sook , Yun Jae Won , Lee Jaebon , Choi Yeon-Kyung , Park Keun-Gyu
Published: March 2022

Background

Macropinocytosis, an important nutrient-scavenging pathway in certain cancer cells, allows cells to compensate for intracellular amino acid deficiency under nutrient-poor conditions. Ferroptosis caused by cysteine depletion plays a pivotal role in sorafenib responses during hepatocellular carcinoma (HCC) therapy. However, it is not known whether macropinocytosis functions as an alternative pathway to acquire cysteine in sorafenib-treated HCC, and whether it subsequently mitigates sorafenib-induced ferroptosis. This study aimed to investigate whether sorafenib drives macropinocytosis induction, and how macropinocytosis confers ferroptosis resistance on HCC cells.

Methods

Macropinocytosis, both in HCC cells and HCC tissues, was evaluated by measuring TMR-dextran uptake or lysosomal degradation of DQ-BSA, and ferroptosis was evaluated via C11-BODIPY fluorescence and 4-HNE staining. Sorafenib-induced ferroptosis and macropinocytosis were validated in tumor tissues taken from HCC patients who underwent ultrasound-guided needle biopsy.

Results

Sorafenib increased macropinocytosis in human HCC specimens and xenografted HCC tissues. Sorafenib-induced mitochondrial dysfunction was responsible for activation of PI3K-RAC1-PAK1 signaling, and amplified macropinocytosis in HCC. Importantly, macropinocytosis prevented sorafenib-induced ferroptosis by replenishing intracellular cysteine that was depleted by sorafenib treatment; this rendered HCC cells resistant to sorafenib. Finally, inhibition of macropinocytosis by amiloride markedly enhanced the anti-tumor effect of sorafenib, and sensitized resistant tumors to sorafenib.

Conclusion

In summary, sorafenib induced macropinocytosis, which conferred drug resistance by mitigating sorafenib-induced ferroptosis. Thus, targeting macropinocytosis is a promising therapeutic strategy to facilitate ferroptosis-based therapy for HCC.

Graphic Abstract
O-Acetyl-L-homoserine production enhanced by pathway strengthening and acetate supplementation in Corynebacterium glutamicum
Authors: Li Ning , Zeng Weizhu , Zhou Jingwen , Xu Sha
Published: March 2022

Background

O-Acetyl-L-homoserine (OAH) is an important potential platform chemical. However, low levels of production of OAH are greatly limiting its industrial application. Furthermore, as a common and safe amino acid-producing strain, Corynebacterium glutamicum has not yet achieved efficient production of OAH.

Results

First, exogenous L-homoserine acetyltransferase was introduced into an L-homoserine-producing strain, resulting in the accumulation of 0.98 g/L of OAH. Second, by comparing different acetyl-CoA biosynthesis pathways and adding several feedstocks (acetate, citrate, and pantothenate), the OAH titer increased 2.3-fold to 3.2 g/L. Then, the OAH titer further increased by 62.5% when the expression of L-homoserine dehydrogenase and L-homoserine acetyltransferase was strengthened via strong promoters. Finally, the engineered strain produced 17.4 g/L of OAH in 96 h with acetate as the supplementary feedstock in a 5-L bioreactor.

Conclusions

This is the first report on the efficient production of OAH with C. glutamicum as the chassis, which would provide a good foundation for industrial production of OAH.
A deep learning pipeline to simulate fluorodeoxyglucose (FDG) uptake in head and neck cancers using non-contrast CT images without the administration of radioactive tracer
Authors: Chandrashekar Anirudh , Handa Ashok , Ward Joel , Grau Vicente , Lee Regent
Published: March 2022

Objectives

Positron emission tomography (PET) imaging is a costly tracer-based imaging modality used to visualise abnormal metabolic activity for the management of malignancies. The objective of this study is to demonstrate that non-contrast CTs alone can be used to differentiate regions with different Fluorodeoxyglucose (FDG) uptake and simulate PET images to guide clinical management.

Methods

Paired FDG-PET and CT images (n = 298 patients) with diagnosed head and neck squamous cell carcinoma (HNSCC) were obtained from The cancer imaging archive. Random forest (RF) classification of CT-derived radiomic features was used to differentiate metabolically active (tumour) and inactive tissues (ex. thyroid tissue). Subsequently, a deep learning generative adversarial network (GAN) was trained for this CT to PET transformation task without tracer injection. The simulated PET images were evaluated for technical accuracy (PERCIST v.1 criteria) and their ability to predict clinical outcome [(1) locoregional recurrence, (2) distant metastasis and (3) patient survival].

Results

From 298 patients, 683 hot spots of elevated FDG uptake (elevated SUV, 6.03 ± 1.71) were identified. RF models of intensity-based CT-derived radiomic features were able to differentiate regions of negligible, low and elevated FDG uptake within and surrounding the tumour. Using the GAN-simulated PET image alone, we were able to predict clinical outcome to the same accuracy as that achieved using FDG-PET images.

Conclusion

This pipeline demonstrates a deep learning methodology to simulate PET images from CT images in HNSCC without the use of radioactive tracer. The same pipeline can be applied to other pathologies that require PET imaging.
Validation of Acromegaly Quality of Life Questionnaire (AcroQoL) for the Iranian population
Authors: Danaei Mina , Bahadorizadeh Leyla , Dehnad Afsaneh , Mohamadzadeh Shirin , Hashemi-Madani Nahid , Khamseh Mohammad E.
Published: March 2022

Background

Acromegaly is a chronic disease significantly affects the physical, emotional, and health-related aspects of patients' life. This study aimed to validate the Acromegaly Quality of Life Questionnaire (AcroQoL) for the Persian-speaking population.

Methods

This cross-sectional study recruited 73 Iranian patients with a confirmed diagnosis of acromegaly. The content validity of the scales was evaluated by an expert panel of eight endocrinologists applying content validity index (CVI) and content validity ratio (CVR). Construct validity was assessed by using confirmatory factor analysis. Internal consistency was assessed on the basis of Cronbach’s alpha, and a goodness-of-fit (GoF) index was calculated to display whether the model fitted the data.

Results

CVI and CVR yielded values of 0.85 and 0.80, respectively (Acceptable CVI: > 0.78 and CVR: > 0.75). The average variances extracted (AVE) from physical and psychological dimensions were 0.520 and 0.462, respectively, exceeding the minimum criterion of 0.40. Cronbach’s alpha for physical and psychological dimensions equaled 0.868 and 0.866, respectively, indicating the adequate internal consistency of multiple items for each construct. The subscales’ R square and path coefficient were greater than the recommended threshold as 0.75 (physical dimension: 0.778, psychological dimension: 0.873), demonstrating the suitability of this criterion. Finally, the GoF value of 0.29 indicated the model's moderate fit.

Conclusions

The findings revealed that the Persian version of AcroQoL is of adequate validity and reliability for evaluating the quality of life of Iranian people with acromegaly.
The magnitude of the partial volume effect in SPECT imaging of the kidneys: a phantom study
Authors: Grings Andreas , Jobic Camille , Kuwert Torsten , Ritt Philipp
Published: March 2022

Background

Single-photon emission computed tomography (SPECT) can cause an over- or underestimation of tissue activity concentration due to limitations in spatial resolution compared to the structures under study. This is commonly referred to as partial volume effect (PVE). Ideally, the PVE should be controlled for and corrected. One such correction method involves determining recovery coefficients (RC) from phantom measurements. In the literature, several studies applying simplified geometries are available. In this study, we aimed to determine kidney PVE for realistic kidney geometries. Furthermore, we proposed a new surrogate metric for predicting the extent of PVE in kidneys.

Material and methods

Based on patients’ CT data, we manufactured fillable phantoms using a 3D-printer. Nine cortex-only and ten whole-parenchyma phantoms were obtained, and one ellipsoidal phantom for comparison. To measure PVE, we placed the phantoms in a torso phantom and filled them with a specified activity concentration. The phantoms’ RCs were determined from fully quantitative SPECT/CT acquisitions at three different target-to-background ratios (TBRs). Additionally, the surface area-to-volume (SA:V) ratio was determined for all phantoms and correlated with RCs.

Results

For SPECT reconstructions with 36 iterations, average RC ± one standard deviation at a 10-to-1 TBR was 76.3 ± 1.5% and 48.4 ± 8.3% for whole-parenchyma and cortex-only phantoms, respectively. The RC for the ellipsoidal phantom was 85.4%. The RC for whole-parenchyma was significantly higher than for cortex-only phantoms (p < 0.01). The RC variance was significantly higher for cortex-only phantoms (p < 0.01). A highly significant correlation of the SA:V ratio and RC was found for all phantoms. (R2 of linear regression was between 0.96 and 0.98.)

Conclusion

Changes in the specific shape of the kidneys cause large changes in PVE magnitude. Therefore, RCs derived from more simple phantoms are most likely insufficient to correct the PVE in patient images. Furthermore, one should account for the fact that intra-renal activity distribution significantly influences the extent of PVE. Additionally, we found that the SA:V ratio excellently models kidney RCs; potentially, this approach could also be applied to other geometries and represents an alternative to full imaging process simulations to determine the extent of PVE.
Emotional competence, attachment, and parenting styles in children and parents
Authors: Mortazavizadeh Zeinab , Göllner Lars , Forstmeier Simon
Published: March 2022

The goal of this study was to examine whether a subject’s emotional competence correlates to attachment styles and parenting styles in children and their parents. The study was conducted with fifty children (9–11 years old) and their parents, both of whose emotional competence (EKF) and parenting style (PAQ) were measured. The attachment styles of parents and children were measured with the Adult Attachment Scale (AAS) and the Bochumer Bindungstest (BoBiTe), respectively. The findings provide initial support to the assumption that attachment is related to emotional competence in parents. This relationship, however, was not significantly correlated in children. In addition, authoritative parenting and permissive parenting were significantly associated with emotional competence in parents. Emotional competence in children showed to be associated with an authoritative parenting style.
Pericapsular nervegroup (PENG) block—a scoping review
Authors: Kaur Gagandeep , Saikia Priyam , Dey Samarjit , Kashyap Nayana
Published: March 2022

The obturator nerve and its accessory branch supplying the hip region, unlike the femoral nerve, are not adequately anaesthetized by conventional regional anaesthetic techniques targeting the hip region. With advancements in ultrasound-guided regional anaesthetic techniques, interests are revived in the field and efforts are being made to block them together. One such successful attempt is the novel peri-capsular nerve group (PENG) block. Consequently, further research on the PENG block began to explore its versatilities. The present study undertakes a scoping review of research on the PENG block in humans for any indication to determine the extent of the research done, the methodologies used, and other practical issues addressed in the research. This will help to identify potential research gaps that should be addressed in the future. PubMed, Google Scholar, Cochrane Library, KoreaMed, Latin American and Caribbean Health Science Literature, and the directory of open access journals were searched with the keyword “PENG block” and “pericapsular nerve group”. Manual search of electronically retrieved papers was also carried out. Among the 67 articles selected in our review, eighteen are case series; twenty-nine are case reports; two are randomized studies; one each of prospective cohort study, review, and cadaveric study; and 15 are editorials. However, only 64 articles were included later due to the retraction of three case reports. Data is insufficient to provide firm recommendations for or against different aspects of the block. The review encourages future work addressing different aspects of the PENG block.
Carbon composites from iron-chelating pyridine nitrogen-rich coordinated nanosheets for oxygen reduction
Authors: Zhang Bing , Guo Hele , Zhang Longsheng , Zhang Xu , Zhang Chao , Liu Tianxi
Published: March 2022

The exploration of a noble-metal-free and nitrogen-doped carbon (M–N/C) composite electrocatalyst for the oxygen reduction reaction (ORR) remains a great challenge. The activities of the M–N/C composite electrocatalysts are mainly affected by the metal active sites, pyridinic nitrogen, and graphitic nitrogen. In the present work, the iron-coordinated self-assembly is proposed for the preparation of iron-chelating pyridine nitrogen-rich coordinated nanosheet (IPNCN) composites as electrocatalysts. Due to the highly conjugated structure of the IPNCN precursor, the pyridine nitrogen elements at both ends of the tetrapyrido [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TP) provide the multiple ligands, and the coordination interactions between the irons and the pyridine nitrogen further improve the thermodynamic stability, where the metal active sites and nitrogen elements are uniformly distributed in the whole structure. The resultant IPNCN composites exhibit excellent ORR performance with an onset potential of 0.93 V and a half potential of 0.84 V. Furthermore, the IPNCN composite electrocatalysts show the higher methanol resistance and electrochemical durability than the commercial Pt/C catalysts. It could be convinced that the as-designed IPNCN composite catalysts would be a promising alternative to the noble metal Pt-based catalysts in the practical applications.
Hydrogen and formate production and utilisation in the rumen and the human colon
Authors: Kelly William J. , Mackie Roderick I. , Attwood Graeme T. , Janssen Peter H. , McAllister Tim A. , Leahy Sinead C.
Published: March 2022

Molecular hydrogen (H2) and formate (HCOO−) are metabolic end products of many primary fermenters in the mammalian gut. Both play a vital role in fermentation where they are electron sinks for individual microbes in an anaerobic environment that lacks external electron acceptors. If H2 and/or formate accumulate within the gut ecosystem, the ability of primary fermenters to regenerate electron carriers may be inhibited and microbial metabolism and growth disrupted. Consequently, H2- and/or formate-consuming microbes such as methanogens and homoacetogens play a key role in maintaining the metabolic efficiency of primary fermenters. There is increasing interest in identifying approaches to manipulate mammalian gut environments for the benefit of the host and the environment. As H2 and formate are important mediators of interspecies interactions, an understanding of their production and utilisation could be a significant entry point for the development of successful interventions. Ruminant methane mitigation approaches are discussed as a model to help understand the fate of H2 and formate in gut systems.
Nontraditional risk factors in chronic kidney disease: correlation between creatinine clearance, Framingham risk score, endothelial dysfunction, and inflammation
Authors: Tawfik Ahmed Mohamed , Tawfik Heba Mohamed
Published: March 2022

Background

Chronic kidney disease became a public health problem increasing healthcare burden. Our aim was to detect the relationship between cardiovascular risk, endothelial dysfunction, inflammation, and kidney function in chronic kidney disease patients and to detect the nontraditional factors affecting the decline in kidney functions.

Methods

A cross-sectional study including 30 male and female patients with chronic kidney disease stages 3–5. Creatinine clearance and Framingham risk score points were calculated. Carotid intimal medial thickness was measured as well as absolute flow mediated dilatation in brachial artery. Highly sensitive C-reactive protein, parathyroid hormone, kidney function tests, and lipid profile were measured.

Results

Framingham risk score points and carotid intimal medial thickness increased significantly with decreasing creatinine clearance (p0.0025, 0.0285) respectively. A significant correlation was found between highly sensitive C-reactive protein and Framingham risk score points but not with carotid intimal medial thickness (p0.0043, 0.2229) respectively. An inverse correlation was found between creatinine clearance and highly sensitive C-reactive protein (p0.0174). Absolute flow mediated dilatation in brachial artery decreases with increasing Framingham risk score points and decreasing creatinine clearance (p0.0044, 0.0269) respectively.

Conclusion

There is correlation between chronic kidney disease and impaired vascular function, subclinical atherosclerosis, and heightened inflammatory response. Chronic kidney disease patients are at increased risk of cardiovascular events with higher [10-]year cardiovascular risk.
Epidemiological trends of mosquito-borne viral diseases in Pakistan
Authors: Imran Muhammad , Ye Jing , Saleemi Muhammad K. , Shaheen Iqra , Zohaib Ali , Chen Zheng , Cao Shengbo
Published: March 2022

Globally, arboviruses are public health problems. Pakistan has seen a fast-paced increase in mosquito-borne Flavivirus diseases such as dengue because of deforestation, climate change, urbanization, poor sanitation and natural disasters. The magnitude and distribution of these diseases are poorly understood due to the lack of a competitive nationwide surveillance system. In dengue-endemic countries, the recent epidemics of chikungunya (CHIKV) and human West Nile virus (WNV) have created panic among the public and are thought to provoke an outbreak of Zika virus (ZIKV) in Pakistan. Recently, hospital-based surveillance has indicated the presence of Japanese encephalitis virus (JEV), which is deeply concerned by developing countries such as Pakistan. The situation could become more devastating because of poorly developed diagnostic infrastructure. To date, no licensed vaccine has been used in Pakistan, and preventive measures are mainly based on vector control. This review provides comprehensive information concerning the association of risk factors with disease occurrence, epidemiological trends, and prediction of the spread of mosquito-borne diseases, attention to new threats of ZIKV, and future perspectives by benchmarking global health policies.