bluuebunny/crossref_metadata_2025 huggingface dataset:
GATA6-AS1 suppresses epithelial–mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability
Authors: Zhou Yunhui , Zhou Xinyi , Ben Qiwen , Liu Ningning , Wang Jiahui , Zhai Yongpeng , Bao Yichen , Zhou Lin
Published: December 2023

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a hypoxic microenvironment, a high rate of heterogeneity as well as a high likelihood of recurrence. Mounting evidence has affirmed that long non-coding RNAs (lncRNAs) participate in the carcinogenesis of PDAC cells. In this study, we revealed significantly decreased expression of GATA6-AS1 in PDAC based on the GEO dataset and our cohorts, and showed that low GATA6-AS1 expression was linked to unfavorable clinicopathologic characteristics as well as a poor prognosis. Gain- and loss-of-function studies demonstrated that GATA6-AS1 suppressed the proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT) process of PDAC cells under hypoxia. In vivo data confirm the suppressive roles of GATA6-AS1/SNAI1 in tumor growth and lung metastasis of PDAC. Mechanistically, hypoxia-driven E26 transformation-specific sequence-1 (ETS1), as an upstream modulatory mechanism, was essential for the downregulation of GATA6-AS1 in PDAC cells. GATA6-AS1 inhibited the expression of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) eraser, and repressed SNAI1 mRNA stability in an m6A-dependent manner. Our data suggested that GATA6-AS1 can inhibit PDAC cell proliferation, invasion, migration, EMT process and metastasis under hypoxia, and disrupting the GATA6-AS1/FTO/SNAI1 axis might be a viable therapeutic approach for refractory hypoxic pancreatic cancers.
RUNX1 knockdown induced apoptosis and impaired EMT in high-grade serous ovarian cancer cells
Authors: Chen Yuanzhi , He Zhicheng , Yang Shuting , Chen Cheng , Xiong Wenyong , He YingYing , Liu Shubai
Published: December 2023

Ovarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.
Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis
Authors: Cao Ting , Ni Rui , Ding Weimin , Ji Xiaoyun , Fan Guo-Chang , Zhang Zhuxu , Peng Tianqing
Published: December 2023

Background

Sepsis-caused multi-organ failure remains the major cause of morbidity and mortality in intensive care units with limited therapeutics. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has been recently reported to be protective in sepsis; however, its therapeutic effects remain to be determined. This study sought to investigate the therapeutic effects of NMN in septic organ failure and its underlying mechanisms.

Methods

Sepsis was induced by feces-injection-in-peritoneum in mice. NMN was given after an hour of sepsis onset. Cultured neutrophils, macrophages and endothelial cells were incubated with various agents.

Results

We demonstrate that administration of NMN elevated NAD+ levels and reduced serum lactate levels, oxidative stress, inflammation, and caspase-3 activity in multiple organs of septic mice, which correlated with the attenuation of heart dysfunction, pulmonary microvascular permeability, liver injury, and kidney dysfunction, leading to lower mortality. The therapeutic effects of NMN were associated with lower bacterial burden in blood, and less ROS production in septic mice. NMN improved bacterial phagocytosis and bactericidal activity of macrophages and neutrophils while reducing the lipopolysaccharides-induced inflammatory response of macrophages. In cultured endothelial cells, NMN mitigated mitochondrial dysfunction, inflammation, apoptosis, and barrier dysfunction induced by septic conditions, all of which were offset by SIRT3 inhibition.

Conclusion

NAD+ repletion with NMN prevents mitochondrial dysfunction and restrains bacterial dissemination while limiting inflammatory damage through SIRT3 signaling in sepsis. Thus, NMN may represent a therapeutic option for sepsis.
An engineered Fc fusion protein that targets antigen-specific T cells and autoantibodies mitigates autoimmune disease
Authors: Janakiraman Mathangi , Leliavski Alexei , Varadarajulu Jeeva , Jenne Dieter , Krishnamoorthy Gurumoorthy
Published: December 2023

Current effective therapies for autoimmune diseases rely on systemic immunomodulation that broadly affects all T and/or B cell responses. An ideal therapeutic approach would combine autoantigen-specific targeting of both T and B cell effector functions, including efficient removal of pathogenic autoantibodies. Albeit multiple strategies to induce T cell tolerance in an autoantigen-specific manner have been proposed, therapeutic removal of autoantibodies remains a significant challenge. Here, we devised an approach to target both autoantigen-specific T cells and autoantibodies by producing a central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG)-Fc fusion protein. We demonstrate that MOG-Fc fusion protein has significantly higher bioavailability than monomeric MOG and is efficient in clearing anti-MOG autoantibodies from circulation. We also show that MOG-Fc promotes T cell tolerance and protects mice from MOG-induced autoimmune encephalomyelitis. This multipronged targeting approach may be therapeutically advantageous in the treatment of autoimmunity.
Coagulation parameters correlate to venous thromboembolism occurrence during the perioperative period in patients with spinal fractures
Authors: Jiao Yong , Mu Xiaohong
Published: December 2023

Background

Venous thromboembolism (VTE) is one of the leading causes of mortality in hospitalized patients. However, whether the coagulation-related parameters of the hospitalized patients could be used to predict the occurrence of VTE in patients with spinal injury surgery remained unclear.

Method

The patients with spinal fractures who met the inclusion and exclusion criteria were enrolled to be analyzed using a retrospective analysis approach. The association of risk factors of enrolled patients and operations to VTE occurrence were analyzed. The activated partial thromboplastin time, prothrombin time, thrombin time, D-dimer (D-D), fibrinogen (FIB) and fibrinogen degradation products (FDP) were detected. ROC and HR analysis were applied to evaluate the correlation of coagulation-related parameters and other parameters to VTE occurrence.

Result

The indicators of D-D, FIB and FDP were significantly elevated in VTE patients compared to non-VTE patients. The multivariate analysis of OR showed that six risk factors, including age ≥ 60, spinal cord injury, postoperative bedtime over 5 days, plasma D-dimer ≥ 0.54 mg/L, plasma fibrinogen ≥ 3.75 g/L and plasma FDP ≥ 5.19 mg/L, were positively correlated to VTE.

Conclusion

The six risk factors, including D-D, FIB, FDP, age ≥ 60, spinal cord injury, and postoperative bedtime over 5 days, could be used to predict the occurrence of VTE.
The effect of extracorporeal shock wave on joint capsule fibrosis based on A2AR-Nrf2/HO-1 pathway in a rat extending knee immobilization model
Authors: Yuan Hai , Wang Kui , Zhang Quan-Bing , Wang Feng , Zhou Yun
Published: December 2023

Joint capsule fibrosis, a common complication of joint immobilization, is mainly characterized by abnormal collagen deposition. The present study aimed to investigate the effect of extracorporeal shock wave therapy (ESWT) on reduced collagen deposition in the joint capsule during immobilization-induced joint capsule fibrosis. Additionally, the potential involvement of the adenosine A2A receptor (A2AR)-Neurotrophic factor e2-related factor 2 (Nrf2)/Haem oxygenase-1 (HO-1) pathway was explored. Thirty 3-month-old male Sprague–Dawley rats were randomly assigned to five groups: control (C), immobilization model (IM), natural recovery (NR), ESWT intervention (EI), and ESWT combined with A2AR antagonist SCH 58261 intervention (CI). After the left knee joints of rats in the IM, NR, EI and CI groups were immobilized using a full-extension fixation brace for 4 weeks, the EI and CI groups received ESWT twice a week for 4 weeks. The CI group was also treated with ESWT following intraperitoneal injection of SCH 58261 (0.01 mg/kg) for 4 weeks. The range of motion of the left knee joint was measured, and the protein levels of collagens I and III, A2AR, phosphorylated-protein kinase A/protein kinase A (p-PKA/PKA), p-Nrf2/Nrf2, and HO-1 were analysed by Western blotting. The IM and NR groups showed significantly greater arthrogenic contracture than the C group (P < 0.05). Compared to the NR group, the EI and CI groups exhibited significant improvement in arthrogenic contracture (P < 0.05). Conversely, the EI group showed lower contracture than the CI group (P < 0.05). Similar results were observed for collagen deposition and the protein levels of collagens I and III. The intervention groups (EI and CI groups) showed higher levels of p-Nrf2/Nrf2 and HO-1 than the NR group (P < 0.05). Moreover, the EI group exhibited higher levels of p-PKA/PKA, p-Nrf2/Nrf2, and HO-1 than the CI group (P < 0.05). However, no significant difference was found in the A2AR levels among the five groups (P > 0.05). ESWT may activate A2AR, leading to the phosphorylation of PKA. Subsequently, Nrf2 may be activated, resulting in the upregulation of HO-1, which then reduces collagen deposition and alleviates immobilization-induced joint capsule fibrosis.
Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology
Authors: Jin Dian , Le Jing , Yang Qianqian , Cai Qianqian , Dai Hui , Luo Liufei , Tong Jiaqi , Shu Wenxiu
Published: December 2023

Background

Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF).

Methods

Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared.

Results

Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids.

Conclusion

Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.
Impact of the COVID-19 pandemic on mental health care and people with mental health conditions in Ethiopia: the MASC mixed-methods study
Authors: Mihretu Awoke , Fekadu Wubalem , Alemu Azeb Asaminew , Amare Beakal , Assefa Dereje , Misganaw Eleni , Ayele Abebaw , Esleman Ousman , Assefa Zewdu , Alem Atalay , Thornicroft Graham , Hanlon Charlotte
Published: December 2023

Background

The COVID-19 pandemic has had far-reaching effects on the mental health of populations around the world, but there has been limited focus on the impact on people with existing mental health conditions in low-income countries. The aim of this study was to examine impact of the pandemic on mental health care and people with mental health conditions in Ethiopia.

Methods

A convergent mixed methods study was conducted. We systematically mapped information from publicly available reports on impacts of the pandemic on mental health care. Monthly service utilisation data were obtained from Amanuel Mental Specialised Hospital, the main psychiatric hospital, and analysed using segmented Poisson regression (2019 vs. 2020). In-depth interviews were conducted with 16 purposively selected key informants. Framework analysis was used for qualitative data. Findings from each data source were integrated.

Results

In the early stages of the pandemic, participants indicated a minimal response towards the mental health aspects of COVID-19. Mental health-related stigma and discrimination was evident. Scarce mental health service settings were diverted to become COVID-19 treatment centres. Mental health care became narrowly biomedical with poorer quality of care due to infrequent follow-up. Households of people with pre-existing mental health conditions in the community reported worsening poverty and decreased access to care due to restricted movement, decreased availability and fear. Lack of reliable medication supplies increased relapse and the chance of becoming chained at home, abandoned or homeless. Caregiver burden was exacerbated. Within mental health facilities, prisons and residential units, infection control procedures did not adequately safeguard those with mental health conditions. Meanwhile, the needs of people with mental health conditions in COVID-19 quarantine and treatment facilities were systematically neglected. Only late in the day were integrated services developed to address both physical and mental health needs.

Conclusions

The COVID-19 pandemic had substantial negative impacts on the lives of people with mental health conditions in Ethiopia. Future emergency response should prioritise the human rights, health, social and economic needs of people with mental health conditions. Integration of mental and physical health care would both expand access to care and increase resilience of the mental health system.
Prenatal diagnosis of mosaic chromosomal aneuploidy and uniparental disomy and clinical outcomes evaluation of four fetuses
Authors: Qin Shengfang , Wang Xueyan , Wang Jin , Xi Na , Yan Mengjia , He Yuxia , Ye Mengling , Zhang Zhuo , Yin Yan
Published: December 2023

Background

Few co-occurrence cases of mosaic aneuploidy and uniparental disomy (UPD) chromosomes have been reported in prenatal periods. It is a big challenge for us to predict fetal clinical outcomes with these chromosome abnormalities because of their highly heterogeneous clinical manifestations and limited phenotype attainable by ultrasound.

Methods

Amniotic fluid samples were collected from four cases. Karyotype, chromosome microarray analysis, short tandem repeats, and whole exome sequencing were adopted to analyze fetal chromosomal aneuploidy, UPD, and gene variation. Meanwhile, CNVseq analysis proceeded for cultured and uncultured amniocytes in case 2 and case 4 and MS-MLPA for chr11 and chr15 in case 3.

Results

All four fetuses showed mosaic chromosomal aneuploidy and UPD simultaneously. The results were: Case 1: T2(7%) and UPD(2)mat(12%). Case 2: T15(60%) and UPD(15)mat(40%). Case 3: 45,X(13%) and genome-wide paternal UPD(20%). Case 4: <10% of T20 and > 90% UPD(20)mat in uncultured amniocyte. By analyzing their formation mechanism of mosaic chromosomal aneuploidy and UPD, at least two adverse genetic events happened during their meiosis and mitosis. The fetus of case 1 presented a benign with a normal intrauterine phenotype, consistent with a low proportion of trisomy cells. However, the other three fetuses had adverse pregnancy outcomes, resulting from the UPD chromosomes with imprinted regions involved or a higher level of mosaic aneuploidy.

Conclusion

UPD is often present with mosaic aneuploidy. It is necessary to analyze them simultaneously using a whole battery of analyses for these cases when their chromosomes with imprinted regions are involved or known carriers of a recessive allele. Fetal clinical outcomes were related to the affected chromosomes aneuploidy and UPD, mosaic levels and tissues, methylation status, and homozygous variation of recessive genes on the UPD chromosome. Genetic counseling for pregnant women with such fetuses is crucial to make informed choices.
Reconstruction of private genomes through reference-based genotype imputation
Authors: Mosca Matthew J. , Cho Hyunghoon
Published: December 2023

Background

Genotype imputation is an essential step in genetic studies to improve data quality and statistical power. Public imputation servers are widely used by researchers to impute their data using otherwise access-controlled reference panels of high-fidelity genomes held by these servers.

Results

We report evidence against the prevailing assumption that providing access to panels only indirectly via imputation servers poses a negligible privacy risk to individuals in the panels. To this end, we present algorithmic strategies for adaptively constructing artificial input samples and interpreting their imputation results that lead to the accurate reconstruction of reference panel haplotypes. We illustrate this possibility on three reference panels of real genomes for a range of imputation tools and output settings. Moreover, we demonstrate that reconstructed haplotypes from the same individual could be linked via their genetic relatives using our Bayesian linking algorithm, which allows a substantial portion of the individual’s diploid genome to be reassembled. We also provide population genetic estimates of the proportion of a panel that could be linked when an adversary holds a varying number of genomes from the same population.

Conclusions

Our results show that genomes in imputation server reference panels can be vulnerable to reconstruction, implying that additional safeguards may need to be considered. We suggest possible mitigation measures based on our findings. Our work illustrates the value of adversarial algorithms in uncovering new privacy risks to help inform the genomics community towards secure data sharing practices.
A blueprint for a multi-disease, multi-domain Bayesian adaptive platform trial incorporating adult and paediatric subgroups: the Staphylococcus aureus Network Adaptive Platform trial
Authors: Mahar Robert K. , McGlothlin Anna , Dymock Michael , Lee Todd C. , Lewis Roger J. , Lumley Thomas , Mora Jocelyn , Price David J. , Saville Benjamin R. , Snelling Tom , Turner Rebecca , Webb Steven A. , Davis Joshua S. , Tong Steven Y. C. , Marsh Julie A. ,   on behalf of the SNAP Global Trial Steering Committee, Bowen Asha , Cheng Matthew , Daneman Nick , Davis Joshua , Goodman Anna , Heriot George , Lee Todd C. , Lewis Roger , Lye David , Marsh Julie , McGlothlin Anna , McQuilten Zoe , Mora Jocelyn , Morpeth Susan , Paterson David , Price David , Roberts Jason , Robinson Owen , Scarborough Matthew , Tong Steven , van Hal Sebastiaan , Walls Genevieve , Webb Steve , Whiteway Lynda , Yahav Dafna
Published: December 2023

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.

Trial registrationNCT05137119. Registered on 30 November 2021.
Challenges of conducting a randomised placebo-controlled trial of spinal surgery: the SUcceSS trial of lumbar spine decompression
Authors: Ho Emma Kwan-Yee , Mobbs Ralph Jasper , van Gelder James Montague , Harris Ian Andrew , Davis Gavin , Stanford Ralph , Beard David John , Maher Christopher Gerard , Prior Joanna , Knox Michael , Anderson David Barrett , Buchbinder Rachelle , Ferreira Manuela Loureiro
Published: December 2023

Although placebo-controlled trials are considered the gold standard for evaluating the efficacy of healthcare interventions, they can be perceived to be controversial and challenging to conduct for surgical treatments. The SUcceSS trial is the first placebo-controlled trial of lumbar decompression surgery for symptomatic lumbar canal stenosis. The SUcceSS trial has experienced common issues affecting the implementation of randomised placebo-controlled surgery trials, accentuated by the COVID-19 pandemic. Using the SUcceSS trial as an example, we discuss key challenges and mitigation strategies specific to the conduct of a randomised placebo-controlled surgical trial. Overall, the key lessons learned were (i) involving key stakeholders early and throughout the trial design phase may increase clinician and patient willingness to participate in a placebo-controlled trial of surgical interventions, (ii) additional resources (e.g. budget, staff time) are likely required to successfully operationalise trials of this nature, (iii) the level of placebo fidelity, timing of randomisation relative to intervention delivery, and nuances of the surgical procedure under investigation should be considered carefully. Findings are based on one example of a placebo-controlled surgical trial; however, researchers may benefit from employing or building from the strategies described and lessons learned when designing or implementing future trials of this nature.
Lipid accumulation mechanism of Amphora coffeaeformis under nitrogen deprivation and its application as a feed additive in Carassius auratus aquaculture
Authors: Cui Yulin , Wang Kang , Zhou Xiuzhi , Meng Chunxiao , Gao Zhengquan
Published: December 2023

Background

Amphora coffeaeformis, a unicellular diatom, can significantly accumulate lipids under nitrogen (N) limitation. However, the molecular mechanism underlying lipid accumulation in A. coffeaeformis remains unknown and its application development is lagging.

Results

This work analyzed the lipid composition of A. coffeaeformis under N deprivation and investigated its mechanism underlying lipid accumulation using RNA-seq. The results showed that the total lipid content of A. coffeaeformis increased from 28.22 to 44.05% after 5 days of N deprivation, while the neutral lipid triacylglycerol (TAG) content increased from 10.41 to 25.21%. The transcriptional profile showed that N deprivation induced wide-ranging reprogramming of regulation and that most physiological activities were repressed, while the upregulation of glycerol-3-phosphate acyltransferase directly determined TAG accumulation. Moreover, we explored the effect of A. coffeaeformis as a food additive on the lipid composition of crucian carp. The results showed that the contents of unsaturated fatty acids in the meat of fish supplemented with A. coffeaeformis were significantly increased, indicating its potential application in animal nutrition for improving meat quality indicators.

Conclusion

The findings shed light on the molecular mechanisms of neutral lipid accumulation and revealed the key genes involved in lipid metabolism in A. coffeaeformis. Moreover, we also confirmed that A. coffeaeformis can be used as feed additive for improving the lipid composition of crucian carp meat, which provided evidence for the biotechnology application of this high-oil microalgae.
Evaluation of subclinical left ventricular systolic dysfunction in obese patients by global myocardial work
Authors: Huang Jun , Li Guang-an , Wang Jing , Jiao Yu-wen , Qian Zhi-feng , Fan Li , Tang Li-ming
Published: December 2023

Objective

To evaluate subclinical LV systolic dysfunction in obese patients by global myocardial work (MW).

Methods

A total of 589 obese patients and 100 normal controls were enrolled in the study. The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were generated by a noninvasive pressure-strain loop (PSL) in apical 3-, 4- and 2-chamber views acquired by two-dimensional echocardiography. All obese patients were divided into three groups: class I obesity (mild) 30–35 kg/m2, class II obesity (moderate) 35–40 kg/m2 and class III obesity (severe) > 40 kg/m2. These values were compared among the three groups. The independent influencing factors of subclinical LV systolic dysfunction in obese patients were explored by constructing a multiple regression model. ROC analysis was performed to determine the performance of MW to detect subclinical LV systolic dysfunction in obese patients.

Results

The absolute value of GLS in obese patients was significantly lower than that in normal controls (P < 0.001). The values of GWI, GCW, GWE and GCW/GWW in obese patients were significantly lower than those in normal controls (P < 0.05), while GWW was significantly larger than that in normal controls (P < 0.001). Subgroup analysis and trend analysis showed that the values of GWI, GCW, GWE and GCW/GWW in severe obese patients were lower than those in moderate obese patients and lower than those in mild obese patients (P < 0.01), while GWW in severe obese patients was larger than that in moderate obese patients and larger than that in mild obese patients (P < 0.05). Female sex, BMI and SBP were independent influencing factors of impaired GWI (β = 0.15, P < 0.001) (β=-0.18, P < 0.001) (β = 0.50, P < 0.001) and GCW (β = 0.17, P < 0.001) (β=-0.19, P < 0.001) (β = 0.57, P < 0.001). ROC analysis showed that the AUC of the combined global MW was significantly higher than the AUCs of the individual indices (P < 0.05).

Conclusion

In this study, we conclude that subclinical LV systolic dysfunction was detected by the novel global MW technique in obese patients. Elevated BMI in obese patients results in an increased risk of subclinical LV systolic dysfunction, although the LVEF is normal. Controlling BMI in obese patients may reduce the impairment to the LV myocardial systolic function. Global MW is a novel and reproducible technique that can be well applied in the clinical evaluation of subclinical LV systolic dysfunction.
Antimicrobial growth promoters approved in food-producing animals in South Africa induce shiga toxin-converting bacteriophages from Escherichia coli O157:H7.
Authors: Ngoma Nomonde F. N. , Malahlela Mogaugedi N. , Marufu Munyaradzi C. , Cenci-Goga Beniamino T. , Grispoldi Luca , Etter Eric , Kalake Alan , Karama Musafiri
Published: December 2023

In this study, four antimicrobial growth promoters, including virginiamycin, josamycin, flavophospholipol, poly 2-propenal 2-propenoic acid and ultraviolet light, were tested for their capacity to induce stx-bacteriophages in 47 Shiga toxin-producing E. coli O157:H7 isolates. Induced bacteriophages were characterized for shiga toxin subtypes and structural genes by PCR, DNA restriction fragment length polymorphisms (RFLP) and morphological features by electron microscopy. Bacteriophages were induced from 72.3% (34/47) of the STEC O157:H7 isolates tested. Bacteriophage induction rates per induction method were as follows: ultraviolet light, 53.2% (25/47); poly 2-propenal 2-propenoic acid, 42.6% (20/47); virginiamycin, 34.0% (16/47); josamycin, 34.0% (16/47); and flavophospholipol, 29.8% (14/47). A total of 98 bacteriophages were isolated, but only 59 were digestible by NdeI, revealing 40 RFLP profiles which could be subdivided in 12 phylogenetic subgroups. Among the 98 bacteriophages, stx2a, stx2c and stx2d were present in 85.7%, 94.9% and 36.7% of bacteriophages, respectively. The Q, P, CIII, N1, N2 and IS1203 genes were found in 96.9%, 82.7%, 69.4%, 40.8%, 60.2% and 73.5% of the samples, respectively. Electron microscopy revealed four main representative morphologies which included three bacteriophages which all had long tails but different head morphologies: long hexagonal head, oval/oblong head and oval/circular head, and one bacteriophage with an icosahedral/hexagonal head with a short thick contractile tail. This study demonstrated that virginiamycin, josamycin, flavophospholipol and poly 2-propenal 2-propenoic acid induce genetically and morphologically diverse free stx-converting bacteriophages from STEC O157:H7. The possibility that these antimicrobial growth promoters may induce bacteriophages in vivo in animals and human hosts is a public health concern. Policies aimed at minimizing or banning the use of antimicrobial growth promoters should be promoted and implemented in countries where these compounds are still in use in animal agriculture.
Feature-enhanced fusion of U-NET-based improved brain tumor images segmentation
Authors: Nizamani Abdul Haseeb , Chen Zhigang , Nizamani Ahsan Ahmed , Shaheed Kashif
Published: December 2023

The field of medical image segmentation, particularly in the context of brain tumor delineation, plays an instrumental role in aiding healthcare professionals with diagnosis and accurate lesion quantification. Recently, Convolutional Neural Networks (CNNs) have demonstrated substantial efficacy in a range of computer vision tasks. However, a notable limitation of CNNs lies in their inadequate capability to encapsulate global and distal semantic information effectively. In contrast, the advent of Transformers, which has established their prowess in natural language processing and computer vision, offers a promising alternative. This is primarily attributed to their self-attention mechanisms that facilitate comprehensive modeling of global information. This research delineates an innovative methodology to augment brain tumor segmentation by synergizing UNET architecture with Transformer technology (denoted as UT), and integrating advanced feature enhancement (FE) techniques, specifically Modified Histogram Equalization (MHE), Contrast Limited Adaptive Histogram Equalization (CLAHE), and Modified Bi-histogram Equalization Based on Optimization (MBOBHE). This integration fosters the development of highly efficient image segmentation algorithms, namely FE1-UT, FE2-UT, and FE3-UT. The methodology is predicated on three pivotal components. Initially, the study underscores the criticality of feature enhancement in the image preprocessing phase. Herein, techniques such as MHE, CLAHE, and MBOBHE are employed to substantially ameliorate the visibility of salient details within the medical images. Subsequently, the UT model is meticulously engineered to refine segmentation outcomes through a customized configuration within the UNET framework. The integration of Transformers within this model is instrumental in imparting contextual comprehension and capturing long-range data dependencies, culminating in more precise and context-sensitive segmentation. Empirical evaluation of the model on two extensively acknowledged public datasets yielded accuracy rates exceeding 99%.
Sensitivity of non-conventional electro-diagnostic techniques to detect neuropathy in patients with hepatitis “C” viral infection
Authors: Gabr Reem M. , Elkholy Saly H. , Basheer Mye A. , Khairy Marwa , El Salmawy Dina A.
Published: December 2023

Background

Hepatitis “C” virus (HCV) infection has become a growing global health concern. Chronic HCV infection is usually accompanied by extra-hepatic manifestations. Peripheral neuropathies are the most common neurological complications. Electrophysiological tests play an important role in diagnosing polyneuropathy and identifying its pathophysiology. This study aimed at highlighting the sensitivity of non-conventional, quantitative, electrophysiological techniques in the detection of neuropathy in patients having HCV infection. Forty-five HCV patients were recruited for this study. Conventional motor and sensory conduction studies (NCS) were initially performed followed by interference pattern analysis (IPA). Two quantitative nerve conduction scores were also studied: motor amplitude score (MAS) and sensory amplitude score (SAS).

Results

In the two patients’ subgroups (having numbness versus having no numbness), MAS showed a significant difference, while the SAS showed a non-significant difference. In the two subgroups (with normal NCS versus those with abnormal/suspected NCS), the MAS and the SAS mean values were significantly different. Also, there was a positive significant correlation found between the IPA mean amplitude and the SAS parameter. Finally, we presented the results of the diagnostic performance of the MAS and the SAS in detecting abnormal NCS.

Conclusions

MAS and/or SAS scores could be used as good screening tools for the detection of neuropathy. We here recommend expanding the non-conventional NCSs to other etiologies of polyneuropathy.
Land cover, land use, climate change and food security
Authors: Bununu Yakubu Aliyu , Bello Ashiru , Ahmed Adamu
Published: December 2023

The article discusses the intricate relationships between land cover and land use change on the one hand and climate on the other. It explores the current state of the climate change debate and submits that evidence abounds that human-induced climate change is indeed happening. It further explains the concepts of land cover and land use and the similarities, differences and relationships between them. The article then goes on to explore the subject of land use and land cover changes and modifications and how these processes can occur as a consequence of climate change and can also be the drivers of climate change. It then discusses how land cover, land use and climate interact to impact food security using secondary data from Nigeria and also outlines other impacts of climate change and their consequences on food security.
Continuous-time modeling of the multivariate relationships between physical activity levels and stationary time in preschool-aged children: an investigation of the ActivityStat hypothesis
Authors: Lamboglia Carminda Goersch , Ruissen Geralyn R. , Kuzik Nicholas , Carson Valerie , Spence John C.
Published: December 2023

Background

The ActivityStat hypothesis proposes that an increase or decrease in physical activity (PA) greater than a certain set point activates behavioural and/or energy compensatory responses to maintain a stable level of total energy expenditure. Few studies have tested this hypothesis in children and even fewer have focused on young children. Therefore, the purpose of this study was to investigate the ActivityStat hypothesis by examining the presence and timeframe of the relationships among PA levels and stationary time (ST) in preschool-aged children.

Methods

A secondary analysis was performed on repeated measurement data (i.e., day-to-day activity) involving 98 preschool-aged children (age: 4.5 ± 0.7 years) in Edmonton, Canada. Participants were asked to wear an ActiGraph wGT3X-BT on the waist for 7 consecutive days to assess PA levels (i.e., light PA [LPA], and moderate-to-vigorous PA[MVPA]) and ST. Bayesian continuous-time structural equation modeling (CT-SEM) was used to examine the relationship between behaviours over time and the timeframe during which these relationships occur.

Results

Each behaviour (i.e., LPA, MVPA, and ST) positively and meaningfully predicted itself at a later time. These relationships persisted up to 0.5 days later, at which point past behaviour no longer meaningfully predicted future behaviour. In contrast, no relationships were observed between the three behaviours.

Conclusions

This is the first study to investigate the ActivityStat hypothesis using Bayesian CT-SEM in preschool-aged children. When simultaneously taking into account all dynamic relationships suggested by the ActivityStat, the findings fail to support the hypothesis.
Genetic Characterization of Primary Mediastinal B-Cell Lymphoma: Pathogenesis and Patient Outcomes
Authors: Noerenberg Daniel , Briest Franziska , Hennch Cornelius , Yoshida Kenichi , Hablesreiter Raphael , Takeuchi Yasuhide , Ueno Hiroo , Staiger Annette M. , Ziepert Marita , Asmar Fazila , Locher Benjamin N. , Toth Erika , Weber Thomas , Amini Rose-Marie , Klapper Wolfram , Bouzani Maria , Poeschel Viola , Rosenwald Andreas , Held Gerhard , Campo Elías , Ishaque Naveed , Stamatopoulos Kostas , Kanellis George , Anagnostopoulos Ioannis , Bullinger Lars , Goldschmidt Neta , Zinzani Pier Luigi , Bödör Csaba , Rosenquist Richard , Vassilakopoulos Theodoros P. , Ott German , Ogawa Seishi , Damm Frederik
Published: December 2023

PURPOSE

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking.

PATIENTS AND METHODS

To elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions.

RESULTS

Whole-genome sequencing revealed a commonly disrupted p53 pathway with nonredundant somatic structural variations (SVs) in TP53-related genes ( TP63, TP73, and WWOX) and identified novel SVs facilitating immune evasion ( DOCK8 and CD83). Integration of mutation and copy-number data expanded the repertoire of known PMBCL alterations (eg, ARID1A, P2RY8, and PLXNC1) with a previously unrecognized role for epigenetic/chromatin modifiers. Multivariable analysis identified six genetic lesions with significant prognostic impact. CD58 mutations (31%) showed the strongest association with worse PFS (hazard ratio [HR], 2.52 [95% CI, 1.50 to 4.21]; P < .001) and overall survival (HR, 2.33 [95% CI, 1.14 to 4.76]; P = .02). IPI high-risk patients with mutated CD58 demonstrated a particularly poor prognosis, with 5-year PFS and OS rates of 41% and 58%, respectively. The adverse prognostic significance of the CD58 mutation status was predominantly observed in patients treated with nonintensified regimens, indicating that dose intensification may, to some extent, mitigate the impact of this high-risk marker. By contrast, DUSP2-mutated patients (24%) displayed durable responses (PFS: HR, 0.2 [95% CI, 0.07 to 0.55]; P = .002) and prolonged OS (HR, 0.11 [95% CI, 0.01 to 0.78]; P = .028). Upon CHOP-like treatment, these patients had very favorable outcome, with 5-year PFS and OS rates of 93% and 98%, respectively.

CONCLUSION

This large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.
John Bunyan in Abolitionist Print Culture
Authors: Kolding Isaac
Published: December 2023

John Bunyan’s The Pilgrim’s Progress (1678) was enormously popular in the nineteenth-century United States. This article shows that abolitionists appropriated that text, as well as the reputation and biography of its author, as a guide to their own political action. References to Bunyan and The Pilgrim’s Progress in abolitionist print culture, including newspapers and book-length responses to The Pilgrim’s Progress, reveal that abolitionists saw Bunyan as a virtuous progenitor who helped to legitimate and unify their political movement while representing both political commitment and religious toleration.
Assessing the potential of Other Effective area-based Conservation Measures (OECMs) for contributing to conservation targets: A global scoping review protocol
Authors: Petza Dimitra , Amorim Eva , Ben Lamine Emma , Colloca Francesco , Dominguez Crisóstomo Esther , Fabbrizzi Erika , Fraschetti Simonetta , Galparsoro Ibon , Giakoumi Sylvaine , Kruse Maren , Stelzenmüller Vanessa , Katsanevakis Stelios
Published: December 2023

This scoping review (ScR) protocol aims to establish the methodological approach for identifying and mapping the evidence regarding the actual contribution of Other Effective area-based Conservation Measures (OECMs) to spatial conservation targets. Emphasis will be placed on examining the research conducted, including the methodologies applied. OECMs, introduced by the Convention on Biological Diversity (CBD) in 2010, refer to areas outside of protected areas, such as fisheries restricted areas, archaeological sites, and military areas, that effectively conserve biodiversity in-situ over the long term. OECMs are recognized rather than designated. Many countries currently endeavor to identify, recognize and report OECMs to the CBD for formal acceptance to support the implementation of spatial conservation targets. Studies that assess the contribution of OECMs to spatial conservation targets will be considered. Potential OECMs with primary, secondary or ancillary conservation objectives established by all sectors in the terrestrial, freshwater and marine realm worldwide will be considered. Peer-reviewed and grey literature will be considered without imposing limitations based on publication year, stage, subject area and source type. Both experimental and observational studies in English, French, German, Greek, Italian, and Spanish will be reviewed. The ScR will follow the Joanna Briggs Institute (JBI) methodology. The protocol will be guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping reviews. The search will encompass bibliographic databases such as Scopus, Web of Science and Google Scholar. Grey literature sources will include databases, pre-print archives and organizational websites. The Covidence platform will be utilized for data management and extraction.
The genome sequence of the Box Bug, Gonocerus acuteangulatus (Goeze, 1778)
Authors: Sivell Olga ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: December 2023

We present a genome assembly from an individual female Gonocerus acuteangulatus (the Box Bug; Arthropoda; Insecta; Hemiptera; Coreidae). The genome sequence is 1,106.2 megabases in span. Most of the assembly is scaffolded into 10 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 15.31 kilobases in length. Gene annotation of this assembly on Ensembl identified 22,286 protein coding genes.
Self-Compassion, Body Satisfaction, and Eating Disorders in Male Collegiate Athletes: A Longitudinal Analysis
Authors:   , Cusack Kaleb W.
Published: December 2023

Research identifies male athletes as a subpopulation at risk for developing eating disorders and disordered eating (ED/DE). Petrie and Greenleaf's sociocultural model proposes that various correlates contribute to the etiology of ED/DE in athletes. Among the correlates, body satisfaction has been identified as a direct precursor to ED/DE symptomatology in male and female athletes. Recent research has noted self-compassion's utility in alleviating the outcomes of poor body image and ED/DE through several pathways. However, researchers have yet to examine self-compassion in relation to body satisfaction and ED/DE in male athletes or the temporal relationship between these variables. This study longitudinally examined the direct and indirect effects of self-compassion on body satisfaction and ED/DE symptomatology in a mixed-sport sample of 452 male collegiate athletes by testing the cross-lagged, temporal relationships among self-compassion, body satisfaction, and ED/DE symptomatology across a four-month time frame. Time 1 self-compassion was neither directly related to Time 2 body satisfaction (β = 0.02, p = .755), nor indirectly to Time 2 ED/DE (β = -0.002, 95% BCaCI [-0.028, 0.014]) when controlling for Time 1 scores. Recent research supports my finding and suggests that the effects of self-compassion on body satisfaction and ED/DE symptomatology may be dependent on gender. In contrast, Time 2 body satisfaction was directly related to Time 2 ED/DE (β = -0.12, p < 0.05), which adds to a substantial body of research in that body satisfaction is a primary antecedent to ED/DE.
The Examination for the Professional Practice of Psychology (EPPP): An Examination of Criterion Validity
Authors:   , Saldana Samantha
Published: December 2023

The Examination for Professional Practice in Psychology (EPPP) is a requirement for licensure as a psychologist across the entire United States as well as in numerous territories and provinces. Despite many longstanding criticisms and findings of bias, the EPPP is being expanded (adding a second, putatively competency-based, portion to the overall exam) and rebranded as the Enhanced EPPP. A review of literature reveals strong skepticism surrounding these developments, particularly with respect to the issue of criterion validity. The current study sought to examine the criterion validity of the EPPP by (1) drawing archival competency assessment data from existing measures (convergent validity) and (2) gathering new neurocognitive and emotional intelligence data, along with demographic data (discriminant validity), with copies of EPPP score reports from individuals who have recently taken the EPPP. Competency ratings did not significantly positively correlate with EPPP scores and, instead, indicated the opposite trend. Analyses also revealed a significant relationship between ethnicity and exam scores, with White individuals scoring higher than other ethnicities. Finally, performance on neurocognitive tests significantly positively correlated with exam scores, indicating that general test taking abilities play a larger role than abilities and competencies unique to the psychology field. Given the gatekeeping role the EPPP plays in the profession of psychology, external validation of the EPPP is of vital importance and was not supported in this study. Implications for the exam and the field are discussed.