bluuebunny/crossref_metadata_2025 huggingface dataset:
Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children
Authors: Schoettler Michelle , Stenger Elizabeth , Spencer Kathleen , Lutterman Deborah , Rumbika Savanah , Jones Jayre , Haight Ann , Parikh Suhag , Qayed Muna , Watkins Benjamin , Krishnamurti Lakshmanan , Williams Kirsten M. , Chonat Satheesh
Published: September 2022

Transplant-associated thrombotic microangiopathy (TA-TMA) and sickle cell disease (SCD) share features of endothelial and complement activation. Thus, we hypothesized that SCD is a risk factor for TA-TMA and that prehematopoietic cellular transplantation (HCT) markers of endothelial dysfunction and complement activation would be higher in patients with SCD. Children who underwent initial haploidentical or matched sibling donor HCT between January 2015 and June 2020 were included in this institutional review board–approved, single institution, retrospective study. Of the 115 children, 52 had SCD, and 63 underwent HCT for non-SCD indications. There was no significant difference in severe grade 3 to 4 acute graft-versus-host disease (GVHD) between recipients of HCT with or without SCD. The non-SCD cohort had significantly more cytomegalovirus-positive recipients, radiation-containing preparative regimens, and peripheral blood stem cell graft sources (P ≤ .05), all described risk factors for developing TA-TMA. Despite this, 7 of 52 patients (13%) with SCD developed TA-TMA compared with 1 of 63 patients (2%) without SCD (P = .015). Risk was highest in those who underwent haploidentical HCT (odds ratio [OR], 33; 95% confidence interval [CI], 1.4-793.2). Adjusting for HLA match, GVHD, post-HCT viral infection, stem cell source, and myeloablation, SCD remained a risk for developing TA-TMA (OR, 12.22; 95% CI, 1.15-129.6). In available pre-HCT samples, there was no difference in complement biomarkers between those with SCD and those without, though patients with SCD did have significantly higher levels of markers of endothelial activation, soluble vascular cell adhesion molecule 1, and P-selectin. In conclusion, children with SCD merit careful screening for TA-TMA after HCT, particularly those receiving a haploidentical HCT.
The outcome of older adults with classic Hodgkin lymphoma in British Columbia
Authors: Cheng Phoebe T. M. , Villa Diego , Gerrie Alina S. , Freeman Ciara L. , Slack Graham W. , Gascoyne Randy D. , Farinha Pedro , Craig Jeffrey W. , Skinnider Brian , Wilson Don , Scott David W. , Connors Joseph M. , Sehn Laurie H. , Savage Kerry J.
Published: September 2022

Outcomes in older adults with classic Hodgkin lymphoma (cHL) have traditionally been poor, in part, related to poor tolerance to standard chemotherapy. Herein, we evaluated the survival of patients with cHL aged ≥60 years in British Columbia in a population-based analysis. From 1961 to 2019, 744 patients with newly diagnosed cHL were identified. With a median follow-up of 9 years, 5-year disease-specific survival (DSS) and overall survival (OS) have improved by decade comparison (both P < .001), remaining stable in the past 20 years (DSS, P = .35; OS, P = .26). In the modern management era (2000-present), 361 of 401 patients (90%) received active therapy for cHL and had a 5-year OS of 60%. For those who received curative-intent therapy (n = 327), the 5-year progression-free survival (PFS), OS, and DSS were 60%, 65%, and 76%, respectively, and estimates were superior in those who were 60 to 69 years of age (72%, 77%, and 83%, respectively) compared with those who were 70 to 79 years of age (54%, 57%, and 70%, respectively) and ≥80 years of age (28%, 39%, and 63%, respectively) (P < .05 for all). Overall, pulmonary toxicity occurred in 58 of 279 patients (21%) treated with bleomycin, with 22 of 58 (38%) occurring after cycles 1 or 2, accounting for 8 of 20 (40%) treatment-related deaths. Outcomes in older adults with cHL have improved in recent decades; however, they remain poor for those aged ≥70 years, even in the modern treatment era. Furthermore, treatment-related toxicity remains a significant concern and use of bleomycin should be avoided in most patients.
A reinforcement learning approach for protein–ligand binding pose prediction
Authors: Wang Chenran , Chen Yang , Zhang Yuan , Li Keqiao , Lin Menghan , Pan Feng , Wu Wei , Zhang Jinfeng
Published: September 2022

Protein ligand docking is an indispensable tool for computational prediction of protein functions and screening drug candidates. Despite significant progress over the past two decades, it is still a challenging problem, characterized by the still limited understanding of the energetics between proteins and ligands, and the vast conformational space that has to be searched to find a satisfactory solution. In this project, we developed a novel reinforcement learning (RL) approach, the asynchronous advantage actor-critic model (A3C), to address the protein ligand docking problem. The overall framework consists of two models. During the search process, the agent takes an action selected by the actor model based on the current location. The critic model then evaluates this action and predict the distance between the current location and true binding site. Experimental results showed that in both single- and multi-atom cases, our model improves binding site prediction substantially compared to a naïve model. For the single-atom ligand, copper ion (Cu2+), the model predicted binding sites have a median root-mean-square-deviation (RMSD) of 2.39 Å to the true binding sites when starting from random starting locations. For the multi-atom ligand, sulfate ion (SO42−), the predicted binding sites have a median RMSD of 3.82 Å to the true binding sites. The ligand-specific models built in this study can be used in solvent mapping studies and the RL framework can be readily scaled up to larger and more diverse sets of ligands.
Plastome structure, phylogenomics, and divergence times of tribe Cinnamomeae (Lauraceae)
Authors: Xiao Tian-Wen , Ge Xue-Jun
Published: September 2022

Background

Tribe Cinnamomeae is a species-rich and ecologically important group in tropical and subtropical forests. Previous studies explored its phylogenetic relationships and historical biogeography using limited loci, which might result in biased molecular dating due to insufficient parsimony-informative sites. Thus, 15 plastomes were newly sequenced and combined with published plastomes to study plastome structural variations, gene evolution, phylogenetic relationships, and divergence times of this tribe.

Results

Among the 15 newly generated plastomes, 14 ranged from 152,551 bp to 152,847 bp, and the remaining one (Cinnamomum chartophyllum XTBGLQM0164) was 158,657 bp. The inverted repeat (IR) regions of XTBGLQM0164 contained complete ycf2, trnICAU, rpl32, and rpl2. Four hypervariable plastid loci (ycf1, ycf2, ndhF-rpl32-trnLUAG, and petA-psbJ) were identified as candidate DNA barcodes. Divergence times based on a few loci were primarily determined by prior age constraints rather than by DNA data. In contrast, molecular dating using complete plastid protein-coding genes (PCGs) was determined by DNA data rather than by prior age constraints. Dating analyses using PCGs showed that Cinnamomum sect. Camphora diverged from C. sect. Cinnamomum in the late Oligocene (27.47 Ma).

Conclusions

This study reports the first case of drastic IR expansion in tribe Cinnamomeae, and indicates that plastomes have sufficient parsimony-informative sites for molecular dating. Besides, the dating analyses provide preliminary insights into the divergence time within tribe Cinnamomeae and can facilitate future studies on its historical biogeography.
Newly reported chloroplast genome of Sinosenecio albonervius Y. Liu & Q. E. Yang and comparative analyses with other Sinosenecio species
Authors: Peng Jing-Yi , Zhang Xiao-Shuang , Zhang Dai-Gui , Wang Yi , Deng Tao , Huang Xian-Han , Kuang Tian-Hui , Zhou Qiang
Published: September 2022

Background

Sinosenecio B. Nordenstam (Asteraceae) currently comprises 44 species. To investigate the interspecific relationship, several chloroplast markers, including ndhC-trnV, rpl32-trnL, matK, and rbcL, are used to analyze the phylogeny of Sinosenecio. However, the chloroplast genomes of this genus have not been thoroughly investigated. We sequenced and assembled the Sinosenecio albonervius chloroplast genome for the first time. A detailed comparative analysis was performed in this study using the previously reported chloroplast genomes of three Sinosenecio species.

Results

The results showed that the chloroplast genomes of four Sinosenecio species exhibit a typical quadripartite structure. There are equal numbers of total genes, protein-coding genes and RNA genes among the annotated genomes. Per genome, 49–56 simple sequence repeats and 99 repeat sequences were identified. Thirty codons were identified as RSCU values greater than 1 in the chloroplast genome of S. albonervius based on 54 protein-coding genes, indicating that they showed biased usage. Among 18 protein-coding genes, 46 potential RNA editing sites were discovered. By comparing these chloroplast genomes' structures, inverted repeat regions and coding regions were more conserved than single-copy and non-coding regions. The junctions among inverted repeat and single-copy regions showed slight difference. Several hot spots of genomic divergence were detected, which can be used as new DNA barcodes for species identification. Phylogenetic analysis of the whole chloroplast genome showed that the four Sinosenecio species have close interspecific relationships.

Conclusions

The complete chloroplast genome of Sinosenecio albonervius was revealed in this study, which included a comparison of Sinosenecio chloroplast genome structure, variation, and phylogenetic analysis for related species. These will help future research on Sinosenecio taxonomy, identification, origin, and evolution to some extent.
The tomato CONSTANS-LIKE protein SlCOL1 regulates fruit yield by repressing SFT gene expression
Authors: Cui Long , Zheng Fangyan , Wang Jiafa , Zhang Chunli , Zhang Dedi , Gao Sunan , Zhang Chenhui , Ye Jie , Zhang Yuyang , Ouyang Bo , Wang Taotao , Hong Zonglie , Ye Zhibiao , Zhang Junhong
Published: September 2022

Background

CONSTANS (CO) and CONSTANS-LIKE (COL) transcription factors have been known to regulate a series of cellular processes including the transition from the vegetative growth to flower development in plants. However, their role in regulating fruit yield in tomato is poorly understood.

Result

In this study, the tomato ortholog of Arabidopsis CONSTANS, SlCOL1, was shown to play key roles in the control of flower development and fruit yield. Suppression of SlCOL1 expression in tomato was found to lead to promotion of flower and fruit development, resulting in increased tomato fruit yield. On the contrary, overexpression of SlCOL1 disturbed flower and fruit development, and significantly reduced tomato fruit yield. Genetic and biochemical evidence indicated that SlCOL1 controls inflorescence development by directly binding to the promoter region of tomato inflorescence-associated gene SINGLE-FLOWER TRUSS (SFT) and negatively regulating its expression. Additionally, we found that SlCOL1 can also negatively regulate fruit size in tomato.

Conclusions

Tomato SlCOL1 binds to the promoter of the SFT gene, down-regulates its expression, and plays a key role in reducing the fruit size.
Takostubo syndrome combined with ventricular septal perforation: a case report
Authors: Yang Kexin , LI Xinghui , Xie Ping , Zhong Xiang , Zhang Yifan , Xiao Chenmeng , Yao Xiaotao , Cai Jia , Lin Meng
Published: September 2022

Background

The precise clinical features and etiologic basis of Takotsubo syndrome remain unclear, although an association with emotional or stressful triggers has been recognized. Ventricular septal perforation is a very rare life-threatening complication.

Case presentation

A 77-year-old female patient presented to the hospital with unrelieved chest tightness and shortness of breath. Three months ago, the patient's electrocardiogram revealed ischemic T wave inversion of the anterior wall, along with an increase in myocardial injury markers. There was no evidence of a ventricular septal defect on echocardiography. The patient was admitted to the respiratory department to treat lung lesions. The electrocardiogram demonstrated dynamic changes following admission, and the myocardial markers returned to normal, but the echocardiography revealed a ventricular septal defect. The initial diagnosis was ventricular septal perforation because of myocardial infarction with acute anterior ST-segment elevation. Coronary angiography revealed no abnormalities, but left ventricular angiography revealed an enlarged apex and VSD, with a right ventricular shunt bundle. Later, cardiac MRI revealed an apical ventricular septal defect. Further inquiry of the patient's medical history revealed that her husband died unexpectedly three months ago, and her daughter was seriously injured in a car accident, causing the patient severe emotional distress. Takotsubo syndrome was then determined in conjunction with the patient's medical history, symptoms, signs, and pertinent examinations. Without using a catheter or a surgical procedure, we managed the patient's medical condition. Two weeks later, the patient was discharged with symptoms improved.

Conclusions

Takotsubo syndrome is comparable to an acute myocardial infarction on clinical and electrocardiographic examination in the absence of significant coronary disease. Although ventricular septal perforation is most commonly associated with acute myocardial infarction, it can also happen following Takotsubo syndrome. Takotsubo syndrome complicated by ventricular septal perforation is easily misdiagnosed. The early recognition and management of this condition can avoid or reduce morbidity and mortality.
Phase II study of carboplatin/nab-paclitaxel/atezolizumab combination therapy for advanced nonsquamous non–small cell lung cancer patients with impaired renal function: RESTART trial
Authors: Shiraishi Yoshimasa , Kishimoto Junji , Shimose Takayuki , Toi Yukihiro , Sugawara Shunichi , Okamoto Isamu
Published: September 2022

Background

 First-line treatment of nonsquamous non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with immune checkpoint inhibitors (ICIs). However, phase III studies of combinations of cytotoxic chemotherapy and ICIs have included only patients with maintained organ function, not those with renal impairment.

Methods

Cytotoxic chemotherapy–naïve advanced nonsquamous NSCLC patients aged 20 years or older with impaired renal function (creatinine clearance of 15 to 45 mL/min) are prospectively registered in this single-arm phase II study and receive combination therapy with carboplatin, nanoparticle albumin-bound (nab-) paclitaxel, and atezolizumab. Individuals with known genetic driver alterations including those affecting EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK are excluded. We plan to enroll 40 patients over 2 years at 32 oncology facilities in Japan. The primary end point is confirmed objective response rate.

Discussion

If the study demonstrates efficacy and safety of carboplatin/nab-paclitaxel/atezolizumab, then this combination regimen may become a treatment option even for nonsquamous NSCLC patients with impaired renal function.

Trial registration

Registered with Japan Registry for Clinical Trials on 25 February 2021 (jRCTs071200102).
Does financial literacy influence preventive health check-up behavior in Japan? a cross-sectional study
Authors: Lal Sumeet , Nguyen Trinh Xuan Thi , Sulemana Abdul-Salam , Khan Mostafa Saidur Rahim , Kadoya Yoshihiko
Published: September 2022

Background

General health check-ups are an important element of healthcare, as they are designed to detect diseases, thereby reducing morbidity and mortality. Recent studies have found that financial literacy promotes preventive healthcare usage and reduces risky health behaviors such as smoking, lack of exercise, and gambling. Based on this evidence, we hypothesize that financial literacy, as a rational decision-making tool, is positively associated with health check-up behavior in Japan.

Methods

We extracted data on financial literacy, the main explanatory variable of this study, from the 2010 wave of the Preference Parameter Study (PPS) of Osaka University. Data on health check-up behavior as a dependent variable, along with control variables, were obtained from the 2011 PPS wave. Our sample focused on Japan’s middle-aged working population (40–64 years), and we applied probit regressions to test our hypothesis.

Results

Our final sample size was 2,208 participants after merging the two datasets. Descriptive statistics show that respondents had moderate financial literacy (mean = 0.62, SD = 0.33), low financial education (mean = 0.17, SD = 0.38), and low participation (mean = 31.75%, SD = 46.56%) in the health check-up. The probit regression analysis showed that financial literacy is insignificantly associated with health check-up behavior in Japan (coefficient = -0.0229; 95% CI: -0.2011—0.1551; p-value = 0.801). However, demographic factors such as being male (coefficient = -0.2299; 95% CI: -0.3649—-0.0950; p-value = 0.001), older (coefficient = 0.0280; 95% CI: 0.0188 – 0.0371; p-value = 0.000), and married (coefficient = 0.3217; 95% CI: 0.0728 – 0.5705; p-value = 0.011), as well as risky health behavior such as smoking (coefficient = -0.2784; 95% CI: -0.4262—-0.1305; p-value = 0.000) are significantly related to health check-up behavior.

Conclusions

Our results suggest that financial literacy insignificantly motivates people to behave rationally and understand the value of health check-ups as a tool for sustainable health.
Household expenditure of smokers and ex-smokers across socioeconomic groups: results from a large nationwide Australian longitudinal survey
Authors: Lal Anita , Mohebi Mohammadreza , White Sarah L. , Scollo Michelle , McCaffrey Nikki
Published: September 2022

Background

Countries with best practice tobacco control measures have experienced significant reductions in smoking prevalence, but socioeconomic inequalities remain. Spending on tobacco products, particularly by low-income groups can negatively affect expenditure on other goods and services. This study aims to compare the household expenditure of adults who smoke tobacco products and those who formerly smoked across socioeconomic groups.

Methods

Daily smokers and ex-smokers were compared using the Household, Income and Labour Dynamics in Australia Survey, over 7 waves. Adults who never smoked were not included. Participants were continuing sample members across waves. Mean number of participants per wave was 2505, 25% were smokers and 75% ex-smokers. The expenditure variables investigated included tobacco products, alcohol, motor vehicle fuel, health practitioners, insurance, education, and meals eaten out. Regression models using the generalized estimating equation technique were employed to compare expenditure data aggregated across the waves by Socioeconomic Index for Areas (SEIFA) quintiles of relative socio-economic advantage/disadvantage while accounting for within-participant autocorrelation. Quintiles are ranked by information such as the income, occupation and access to material and social resources of the residents.

Results

Smokers from all quintiles spent significantly less per year on meals out, education and insurance than ex-smokers (p < 0.001). Smokers from quintiles 2–5 spent less on groceries, medicines, and health practitioners (p < 0.01). Smokers from quintiles 1 and 2 (most disadvantaged), spent less on motor vehicle fuel than ex-smokers ($280;95%CI: $126–$434), ($213;95%CI: $82–$344). Smokers from quintiles 2 and 3 spent more on alcohol ($212;95%CI: $86–$339), ($231.8;95%CI: $94–$370) than ex-smokers. Smokers from the least disadvantaged groups spent less on clothing than ex-smokers ($348;95%CI: $476–$221), ($501; 95%CI: $743–$258). Across the whole sample, smokers spent more than ex-smokers on alcohol ($230;95%CI:$95–$365) and less on meals out ($361;95%CI:$216–$379), groceries ($529;95%CI:$277–$781), education ($456;95%CI:$288–$624), medicine ($71;95%CI:$38–$104), health practitioners ($345;95%CI:$245–$444) and insurance ($318;95%CI:$229–$407).

Conclusions

Smoking cessation leads to reallocation of spending across all socioeconomic groups, which could have positive impacts on households and their local communities. Less spending on alcohol by ex-smokers across the whole sample could indicate a joint health improvement associated with smoking cessation.
Prevalence and risk factors of general and abdominal obesity and hypertension in rural and urban residents in Bangladesh: a cross-sectional study
Authors: Ali Nurshad , Mohanto Nayan Chandra , Nurunnabi Shaikh Mirja , Haque Tangigul , Islam Farjana
Published: September 2022

Background

Obesity and hypertension are global health concerns. Both are linked with increased risks of all-cause and cardiovascular mortality. Several early studies reported the prevalence of obesity and hypertension in Bangladeshi adults, but the associated factors in this country population are not clear yet. We aimed to estimate the prevalence and related risk factors of general and abdominal obesity and hypertension in rural and urban adults in Bangladesh.

Methods

In this cross-sectional study, data (n = 1410) was collected on rural (n = 626) and urban (n = 784) adults from eight divisional regions of Bangladesh. Both anthropometric and socio-demographic measurements were recorded in a standardized questionnaire form. General and abdominal obesity were defined based on WHO proposed cut-off values and hypertension was defined by SBP ≥ 140 mmHg and/or, DBP ≥ 90 mmHg and/or, intake of anti-hypertensive drugs at the time of data collection. Multivariable logistic regression analyses were performed to assess the relationship of general and abdominal obesity and hypertension with various factors.

Results

The overall prevalence of general obesity, abdominal obesity and hypertension was 18.2, 41.9 and 30.9%, respectively. The women had a higher prevalence of general obesity (25.2%), abdominal obesity (56.1%) and hypertension (32.3%) compared to the men (12.2, 29.0, and 29.7%, respectively). The prevalence of both general and abdominal obesity was higher in urban participants (21.7 and 46.6%, respectively) than in the rural participants (13.8 and 35.1%, respectively), whereas, the rural participants had a higher prevalence of hypertension (35.1%) compared to the urban participants (27.5%). In geographical region comparison, the prevalence of general and abdominal obesity and hypertension were higher in participants enrolled from Dhaka (30.8%), Khulna (63.6%) and Mymensingh (43.5%) regions, respectively compared to other regions. In regression analysis, increased age, place of residence and less physical activity were positively associated with the increased risk of both types of obesity and hypertension. The analysis also showed a significant positive association between high BMI and an increased risk of hypertension.

Conclusion

This study shows a high prevalence of obesity and hypertension in rural and urban adults. Increased age, inadequate physical activity and place of residence were significant determinants of general and abdominal obesity and hypertension. A comprehensive intervention program focusing on modifiable risk factors such as lifestyles and food habits is needed to increase awareness and prevent the burden of obesity and hypertension in the Bangladeshi population.
Diagnosis and treatment of left ureteral injury as a rare complication of oblique lumbar interbody fusion surgery: a case report and literature review
Authors: Wang Weiheng , Xiao Bing , Huang Xiaodong , Yu Jiangming , Xi Yanhai , Xu Guohua , Ye Xiaojian
Published: September 2022

Background

Oblique lumbar interbody fusion (OLIF) surgery has been performed as a minimally invasive lateral lumbar fusion technique in recent years. Reports of operative complications of OLIF are limited, and there are fewer reports of ureteral injuries.

Case presentation

A 62-year-old Chinese woman diagnosed with "lumbar spondylolisthesis (L4 forward slip, I degree)" underwent OLIF treatment. The surgical decompression process was smooth, and the cage was successfully placed. After the expansion sleeve of OLIF was removed, clear liquid continuous outflow from the peritoneum was found. The patient was diagnosed with a ureteral injury. The urological surgeon expanded the original incision, and left ureteral injury anastomosis and ureteral stent implantation were performed. The patient was changed to the prone position and a percutaneous pedicle screw was placed in the corresponding vertebral body. The patient was indwelled with a catheter for 2 weeks, and regular oral administration of levofloxacin to prevent urinary tract infection. After 2 months, the double J tube was removed using a cystoscope. One year after surgery, the symptoms of lumbar back were significantly improved, and there were no urinary system symptoms. However, the patient needed an annual left ureter and kidney B-ultrasound.

Conclusion

Ureteral injury is a rare complication and is easily missed in OLIF surgery. If the diagnosis is missed, the consequences can be serious. Patients should undergo catheterization before the operation and hematuria should be observed during the operation. We emphasize the careful use of surgical instruments to prevent intraoperative complications. In addition, after withdrawing the leaf in the operation, it is necessary to carefully observe whether a clear liquid continues to leak. If ureteral injury is found, one-stage ureteral injury repair operation should be performed to prevent ureteral stricture.
Apoptosis evasion via long non-coding RNAs in colorectal cancer
Authors: Irfan Muhammad , Javed Zeeshan , Khan Khushbukhat , Khan Naila , Docea Anca Oana , Calina Daniela , Sharifi-Rad Javad , Cho William C.
Published: September 2022

Long non-coding RNA (LncRNA) is a novel and diverse class of regulatory transcripts that are frequently dysregulated in numerous tumor types. LncRNAs are involved in a complicated molecular network, regulating gene expression, and modulating diverse cellular activities in different cancers including colorectal cancer (CRC). Evidence indicates that lncRNAs can be used as a potential biomarker for the prognosis and diagnosis of CRC as they are aberrantly expressed in CRC cells. The high expression or silencing of lncRNAs is associated with cell proliferation, invasion, metastasis, chemoresistance and apoptosis in CRC. LncRNAs exert both pro-apoptotic and anti-apoptotic functions in CRC. The expression of some oncogene lncRNAs is upregulated which leads to the inhibition of apoptotic pathways, similarly, the tumor suppressor lncRNAs are downregulated in CRC. In this review, we describe the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in CRC. Furthermore, we also discussed the different apoptotic pathways in normal cells and the mechanisms by which CRC evade apoptosis.
Prevalence of G6PD deficiency and distribution of its genetic variants among malaria-suspected patients visiting Metehara health centre, Eastern Ethiopia
Authors: Shenkutie Tassew Tefera , Nega Desalegn , Hailu Asrat , Kepple Daniel , Witherspoon Logan , Lo Eugenia , Negash Meshesha Tsigie , Adamu Aderaw , Gebremichael Shewayiref Geremew , Gidey Bokretsion , Tasew Geremew , Feleke Sindew M. , Kebede Tadesse
Published: September 2022

Background

Glucose-6-phosphate dehydrogenase (G6PD) is cytosolic enzyme, which has a vital role for the integrity and functioning of red blood cells. Lower activity of this enzyme leads to the occurrence of acute haemolytic anaemia after exposure to oxidative stressors like primaquine. Primaquine is an important drug for the radical cure of Plasmodium vivax and blocking transmission of Plasmodium falciparum, and thereby enhancing malaria elimination. However, there is a need to identify G6PD deficient individuals and administer the drug with caution due to its haemolytic side effects. The main objective of this study is to determine the prevalence of G6PD deficiency among malaria-suspected individuals.

Methods

A facility-based cross-sectional study was conducted from September 2020 to September 2021 in Metehara Health Centre, Eastern Ethiopia. A structured questionnaire was used to collect the socio-demographic and clinical information of the study participants. Capillary and venous blood samples were collected based on standard procedures for onsite screening, dried blood spot preparation, and malaria microscopy. The G6PD enzyme activity was measured by careSTART™ G6PD biosensor analyzer. Data was entered and analysed by SPSS.

Results

A total of 498 study participants were included in the study, of which 62% (309) were males. The overall prevalence of G6PD deficiency based on the biosensor screening was 3.6% (18/498), of which 2.9% and 4.8% were males and females, respectively. Eleven of the G6PD deficient samples had mutations confirmed by G6PD gene sequencing analysis. Mutations were detected in G267 + 119C/T, A376T, and ChrX:154535443. A significant association was found in sex and history of previous malaria infection with G6PD deficiency.

Conclusions

The study showed that the G6PD deficient phenotype exists in Metehara even if the prevalence is not very high. G267 + 119C/T mutation is the predominant G6PD variant in this area. Therefore, malaria patient treatment using primaquine should be monitored closely for any adverse effects.
Health-related quality of life in severe psychotic disorders during integrated care: 5-year course, prediction and treatment implications (ACCESS II)
Authors: Rohenkohl Anja Christine , Daubmann Anne , Gallinat Jürgen , Karow Anne , Kraft Vivien , Rühl Friederike , Schöttle Daniel , Lambert Martin , Schröter Romy
Published: September 2022

Purpose

Studies on outcomes mapping Quality of Life (QoL) as patient-reported outcome over a longer period in severe psychotic disorders are scarce. However, such data would be particularly important for structuring, implementing and operating effective and efficient care models and for promoting satisfaction with care, service engagement and adherence.

Methods

The ACCESS II study is a prospective long-term study of an integrated care model for people with severe psychotic disorders. The model includes Therapeutic Assertive Community Treatment within a cross-sectoral and interdisciplinary network. This publication analyses the course of QoL assessed with the Q-LES-Q-18 using a mixed model for repeated measures.

Results

Mapping the course of QoL in N = 329 participants, there is a significant increase in the first 6 weeks of treatment (early course). Comparison to a published norm show significant lower QoL for severe psychotic disorders. The variable having a traumatic event before the age of 18 was significantly negatively associated with QoL. A decrease in the severity of depressive as well as in positive symptomatology in the first six weeks after admission was associated with increase of QoL.

Conclusion

Results indicate that the overall symptom burden at time of inclusion is not decisive for the perceived QoL in the long-term course while the reduction in the severity of depressive and positive symptoms is important. This means focusing even more on the treatment of depressive symptoms and include traumatherapeutic aspects in the long-term treatment of severe psychotic disorders if needed.

Trail registration

ClinicalTrials.gov (identifier: NCT01888627).
THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours
Authors: Sun Jianyi , Zhang Qiang , Sun Xiangfei , Xue Anwei , Gao Xiaodong , Shen Kuntang
Published: September 2022

Background

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and are characterized by activating mutations of c-KIT or PDGFRa receptor tyrosine kinases (RTKs). Despite the clinical success of tyrosine kinase inhibitors (TKIs), more than half of GIST patients develop resistance due to a second mutation. Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of CDK-activating kinase (CAK), and it plays an important role in the regulation of cell cycle transitions and gene transcription. THZ1, a CDK7 inhibitor, exhibits a dose-dependent inhibitory effect in various cancers.

Methods

Data from the public GEO database and tissue microarray were used to analyse the gene expression levels of CDKs in GISTs. The impact of CDK7 knockdown and the CDK7 inhibitor THZ1 on GIST progression was investigated in vitro using CCK-8, colony formation, and flow cytometry assays and in vivo using a xenograft mouse model. RNA sequencing was performed to investigate the mechanism of GIST cell viability impairment mediated by THZ1 treatment.

Results

Our study demonstrated that CDK7 is relatively overexpressed in high-risk GISTs and predicts a poor outcome. A low concentration of THZ1 exhibited a pronounced antineoplastic effect in GIST cells in vivo and in vitro. Moreover, THZ1 exerted synergistic anticancer effects with imatinib. THZ1 treatment resulted in transcriptional modulation by inhibiting the phosphorylation of Ser2, Ser5, and Ser7 within RNA polymerase II (RNAPII). c-KIT, an oncogene driver of GIST, was transcriptionally repressed by THZ1 treatment or CDK7 knockdown. Transcriptome sequencing analysis showed that OSR1 acts as a downstream target of CDK7 and regulates c-KIT expression. Taken together, our results highlight elevated CDK7 expression as a predictor of poor outcome in GIST and present the combination of CDK7 and RTK inhibitors as a potent therapeutic strategy to improve the efficacy of GIST treatment.
Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases
Authors: Boyd Rachel J. , Avramopoulos Dimitri , Jantzie Lauren L. , McCallion Andrew S.
Published: September 2022

Multifactorial diseases are characterized by inter-individual variation in etiology, age of onset, and penetrance. These diseases tend to be relatively common and arise from the combined action of genetic and environmental factors; however, parsing the convoluted mechanisms underlying these gene-by-environment interactions presents a significant challenge to their study and management. For neurodegenerative disorders, resolving this challenge is imperative, given the enormous health and societal burdens they impose. The mechanisms by which genetic and environmental effects may act in concert to destabilize homeostasis and elevate risk has become a major research focus in the study of common disease. Emphasis is further being placed on determining the extent to which a unifying biological principle may account for the progressively diminishing capacity of a system to buffer disease phenotypes, as risk for disease increases. Data emerging from studies of common, neurodegenerative diseases are providing insights to pragmatically connect mechanisms of genetic and environmental risk that previously seemed disparate. In this review, we discuss evidence positing inflammation as a unifying biological principle of homeostatic destabilization affecting the risk, onset, and progression of neurodegenerative diseases. Specifically, we discuss how genetic variation associated with Alzheimer disease and Parkinson disease may contribute to pro-inflammatory responses, how such underlying predisposition may be exacerbated by environmental insults, and how this common theme is being leveraged in the ongoing search for effective therapeutic interventions.
Central nervous system aspergillosis misdiagnosed as Toxoplasma gondii encephalitis in a patient with AIDS: a case report
Authors: Yang Hong-Hong , He Xue-Jiao , Nie Jing-Min , Guan Shao-Shan , Chen Yao-Kai , Liu Min
Published: September 2022

Background

Patients with acquired immunodeficiency syndrome (AIDS) tend to suffer from several central nervous system (CNS) infections due to hypoimmunity. However, CNS aspergillosis (CNSAG) is extremely rare and difficult to diagnose. Thus, it is easily misdiagnosed.

Case presentation

We reported a 47-year-old male AIDS patient with ghosting vision and anhidrosis on the left head and face. He was accordingly diagnosed with Toxoplasma gondii encephalitis (TE) at other hospitals, for which he received regular anti-Toxoplasma gondii and anti-human immunodeficiency virus (anti-HIV) treatment. Then, the patient was transferred to our hospital due to a lack of any improvement with the prescribed treatment. The patient's neurological examination revealed no abnormalities at admission, only a slight change in the cerebrospinal fluid. His cranial magnetic resonance imaging (MRI) revealed multiple abnormal signals in the brain parenchyma, and his blood was positive for Toxoplasma gondii IgG antibody. The initial diagnosis at our hospital was also TE. Considering the poor efficacy of anti-TE treatment, cerebrospinal fluid metagenomics next-generation sequencing (mNGS) was performed, but no pathogenic bacteria were detected. However, Aspergillus fumigatus was detected in the cerebrospinal fluid via targeted next-generation sequencing (tNGS) and bronchoalveolar alveolar lavage fluid via mNGS. The diagnosis was accordingly revised to CNSAG combined with his other clinical manifestations. After administering voriconazole antifungal therapy, the patient’s symptoms were relieved, with improved absorption of the intracranial lesions.

Conclusions

The present case experience indicates the need for clinicians to strengthen their understanding of CNSAG. Moreover, for patients with diagnostic difficulties, early mNGS and tNGS (using biological samples with only a few pathogens) are helpful for early diagnosis and treatment, potentially allowing patients to achieve favorable outcomes.
SARS-CoV-2 infection in pediatric population before and during the Delta (B.1.617.2) and Omicron (B.1.1.529) variants era
Authors: Khemiri Haifa , Ayouni Kaouther , Triki Henda , Haddad-Boubaker Sondes
Published: September 2022

Background

COVID-19, the coronavirus disease that emerged in December 2019, caused drastic damage worldwide. At the beginning of the pandemic, available data suggested that the infection occurs more frequently in adults than in infants. In this review, we aim to provide an overview of SARS-CoV-2 infection in children before and after B.1.617.2 Delta and B.1.1.529 Omicron variants emergence in terms of prevalence, transmission dynamics, clinical manifestations, complications and risk factors.

Methods

Our method is based on the literature search on PubMed, Science Direct and Google Scholar. From January 2020 to July 2022, a total of 229 references, relevant for the purpose of this review, were considered.

Results

The incidence of SARS-CoV-2 infection in infants was underestimated. Up to the first half of May, most of the infected children presented asymptomatic or mild manifestations. The prevalence of COVID-19 varied from country to another: the highest was reported in the United States (22.5%). COVID-19 can progress and become more severe, especially with the presence of underlying health conditions. It can also progress into Kawasaki or Multisystem Inflammatory Syndrome (MIS) manifestations, as a consequence of exacerbating immune response. With the emergence of the B.1.617.2 Delta and B.1.1.529 Omicron variants, it seems that these variants affect a large proportion of the younger population with the appearance of clinical manifestations similar to those presented by adults with important hospitalization rates.

Conclusion

The pediatric population constitutes a vulnerable group that requires particular attention, especially with the emergence of more virulent variants. The increase of symptomatic SARS-CoV-2 infection and hospitalization rate among children highlights the need to extend vaccination to the pediatric population.
Systematic review of products with potential application for use in the control of Campylobacter spp. in organic and free-range broilers
Authors: Lassen Brian , Helwigh Birgitte , Kahl Petersen Channie , Ellis-Iversen Johanne
Published: September 2022

Campylobacter spp. are some of the most important food-borne zoonoses in Europe and broiler meat is considered the main source of Campylobacter infections. Organic and free-range broilers have access to outdoor reservoirs of Campylobacter and are more frequently infected at slaughter than the conventional broiler flocks. Limitations to biosecurity and treatment options in these production types calls for additional solutions. This review examines intervention methods with sufficient strength and quality, which are able to reduce the load of Campylobacter safely and efficiently and discuss their applicability in organic and free-range broiler production. Four different products passed the inclusion criteria and their quality examined: ferric tyrosine chelate, a prebiotic fermentation product of Saccharomyces cerevisiae, short-chain fatty acid butyrate coated on microbeads added to feed, and a mix of organic acids added to the drinking water. Though potential candidates for reducing Campylobacter in broilers were identified, there is a lack of large scale intervention studies that demonstrate an effect under field conditions of a free-range broiler production.
Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial
Authors: Afolabi Bosede B. , Babah Ochuwa A. , Akinajo Opeyemi R. , Adaramoye Victoria O. , Adeyemo Titilope A. , Balogun Mobolanle , Banke-Thomas Aduragbemi , Quao Rachel A. , Olorunfemi Gbenga , Abioye Ajibola I. , Galadanci Hadiza S. , Sam-Agudu Nadia A.
Published: September 2022

Background

Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa.

The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose.

Methods

This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20–32 weeks’ gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum.

Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks’ gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks’ gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions.

Discussion

The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned.

Trial registration

ISRCTN registry ISRCTN63484804. Registered on 10 December 2020

Clinicaltrials.govNCT04976179. Registered on 26 July 2021

The current protocol version is version 2.1 (080/080/2021).
Label-free quantitative proteomic analysis of ethanamizuril-resistant versus -sensitive strains of Eimeria tenella
Authors: Cheng Peipei , Wang Chunmei , Zhang Lifang , Fei Chenzhong , Liu Yingchun , Wang Mi , Zhang Keyu , Wang Xiaoyang , Gu Feng , Xue Feiqun
Published: September 2022

Background

Avian coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The extensive use of anticoccidial drugs has resulted in an increase in drug resistance. Ethanamizuril (EZL) is a novel triazine with high anticoccidial activity.

Methods

We compared oocyst production and sporulation between EZL-sensitive (S) and EZL-resistant Eimeria tenella strains (R10 and R200) and used label-free quantitative proteomics to identify differentially expressed proteins (DEPs) between these strains.

Results

We generated two EZL-resistant E. tenella strains: strain R10, which was induced using a constant dose of 10 mg EZL/kg poultry feed, and strain R200, which was generated by gradually increasing the EZL dosage to 200 mg EZL/kg poultry feed. With an increase in resistance, the total oocyst output decreased, but the percentage of sporulation did not change significantly. We identified a total of 7511 peptides and 1282 proteins, and found 152 DEPs in the R10 strain versus the S strain, 426 DEPs in the R200 strain versus the S strain and 494 DEPs in the R200 strain versus the R10 strain. When compared with the S strain, 86 DEPs were found to have consistent trends in both resistant strains. The DEPs were primarily involved in ATP and GTP binding, invasion, and membrane components. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEPs suggested that they are involved in transcription and translation processes. Protein–protein interaction network analysis of the 86 DEPs showed that 10 proteins were hubs in the functional interaction network (≥ 8 edges) and five of them were ribosomal proteins.

Conclusions

The results of the present study indicate that the resistance mechanisms of E. tenella against EZL might be related to the transcriptional and translational processes, especially in the factors that inhibit the growth of parasites. The DEPs found in this study provide new insights into the resistance mechanisms of E. tenella against EZL. Further research on these potential targets holds promise for new chemotherapeutic approaches for controlling E. tenella infections.

Graphical Abstract
Some new φ-fixed point and φ-fixed disc results via auxiliary functions
Authors: Sun Yan , Liu Xiao-lan , Deng Jia , Zhou Mi , Zhang Huan
Published: September 2022

In this paper, we first introduce several new contractions by some auxiliary functions. Then we establish some φ-fixed point results for $(\gamma ,\psi ,\varphi ,\phi )$
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contractions and almost-$(\gamma ,\psi , \varphi ,\phi )$
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contractions and φ-fixed disc results for $(\psi ,\varphi ,\phi )_{x_{0}}$

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type 3 contractions in metric spaces. We generalize some existing φ-fixed point and φ-fixed circle results in the literature. Further, we give some examples to demonstrate the usefulness of our results and investigate the existence and uniqueness of solutions of nonlinear integral equations.