bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical cancer screening among HIV-positive women in urban Uganda: a cross sectional study
Authors: Sarah Maria Najjuka , Olwit Connie , Kaggwa Mark Mohan , Nabirye Rose Chalo , Ngabirano Tom Denis
Published: May 2022

Background

Women living with Human Immunodeficiency Virus (HIV) are at a high risk for early development of cervical cancer. Adherence to cervical cancer prevention strategies in this population is vital for the early detection and treatment of cervical cancer. This study aimed to determine the prevalence and factors associated with cervical cancer screening among HIV-positive women attending an urban HIV care center in Uganda.

Methods

This cross-sectional study included 205 HIV-positive women receiving care at an urban HIV care center. An interviewer-administered questionnaire was used to capture sociodemographic information, history of screening for cervical cancer, and reproductive health characteristics. Logistic regression analysis was used to determine the factors associated with cervical cancer screening.

Results

Of the 205 HIV-positive women with a mean age of 37.5 ± 8.87 that participated in the study, majority (n = 201, 98%) were aware of cervical cancer screening. Ninety participants (44%) had ever been screened for cervical cancer and only 33 (16.1%) had been screened in the past year. Obtaining information about cancer of the cervix and cervical cancer screening from health care professionals was significantly associated with higher levels of cervical cancer screening (adjusted odds ratio = 5.61, 95% confidence interval: 2.50–12.61, p value < 0.001).

Conclusion

This study highlights the low prevalence of cervical cancer screening among HIV-positive women and underscores the role of health professionals as an effective source of information on cervical cancer and cervical cancer screening. Patient education programs in HIV prevention and care facilities should emphasize cervical cancer screening messages to enhance the uptake of screening services.
Faculty appointment and promotion in Taiwan’s medical schools, a systematic analysis
Authors: Yeh Jiunn-Tyng , Shulruf Boaz , Lee Hsin-Chen , Huang Pin-Hsiang , Kuo Wen-Hua , Hwang Tyzh-Chang , Chen Chen-Huan
Published: May 2022

Background

A rigorous faculty appointment and promotion (FAP) system is vital for the success of any academic institution. However, studies examining the FAP system in Asian universities are lacking. We surveyed the FAP policies of Taiwan’s medical schools and identified an overreliance on the CJA score (manuscript Category, Journal quality, and Author order). The potential shortcomings of this metric and recommendations for refinement were discussed.

Methods

We obtained the FAP documents from all 12 medical schools in Taiwan, and analyzed their use of traditional versus non-traditional criteria for FAP according to a published methodology. The influence of the journal impact factor (JIF) on the FAP process was quantified by comparing its relative weight between papers with two extreme JIFs. To better understand the research impact and international standing of each school, we utilized the public bibliographic database to rank universities by the number of papers, and the proportions of papers within the top 10% or 50% citation.

Results

Compared with other countries, Taiwan’s medical schools focus more on the quantifiable quality of the research, mostly using a “CJA” score that integrates the category, JIF or ranking, and authorship of a paper, with the JIF being the most influential factor. The CJA score for an article with a JIF of 20 can be up to three times the threshold for promotion to Assistant Professor. The emphasis on JIF is based on a presumed correlation between JIF and citation counts. However, our analysis shows that Taiwan’s medical schools have lower-than-average citation counts despite a competitive rank in the number of publications.

Conclusions

The JIF plays an unrivaled role in determining the outcome of FAP in Taiwan’s medical schools, mostly via the CJA system. The questionable effectiveness of the current system in elevating the international standing of Taiwan’s higher-education institutions calls for a re-examination of the FAP system. We recommend a reduction in the relative importance of CJA score in the FAP system, adopting more rigorous metrics such as the h-index for evaluating research quality, and supporting more research aimed at improving the FAP system.
Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial
Authors: Song Zhengbo , Lou Guangyuan , Wang Yina , Yang Zhiping , Wang Wenxian , Ji Yongling , Chen Shiqing , Xu Chunwei , Hu Xiao , Zhang Yiping
Published: May 2022

Background

Thymic epithelial tumors (TETs) are rare malignancies and the treatment options are limited. We aimed to evaluate the efficacy and safety of apatinib, an angiogenesis inhibitor, in advanced TETs.

Methods

This was an open-label, single-arm, phase II trial at three centers in China. Patients with TET who had progressed after failure of at least one line of platinum-based chemotherapy were enrolled. Patients received apatinib 500 mg orally per day. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety.

Results

From June 29, 2017, to April 18, 2019, 25 patients were enrolled. At data cut off (September 30, 2021), one patient achieved complete response, nine achieved partial response, and 11 achieved stable disease, with an ORR of 40% (95% CI 21–61%) and DCR of 84% (95% CI 64–95%). The median PFS was 9.0 (95% CI 5.4–12.6) months. The median OS was 24.0 (95% CI 8.2–39.8) months. All patients reported treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred 26 times in 15 patients. No grade 4 or 5 toxicities occurred.

Conclusions

This is the first trial of apatinib for the treatment of TETs. Apatinib showed promising antitumor activity and the toxicities were tolerable and manageable.
Reliability analysis of exonic-breakpoint fusions identified by DNA sequencing for predicting the efficacy of targeted therapy in non-small cell lung cancer
Authors: Li Weihua , Wan Rui , Guo Lei , Chang Geyun , Jiang Dong , Meng Lin , Ying Jianming
Published: May 2022

Background

Diverse genomic breakpoints of fusions that localize to intronic, exonic, or intergenic regions have been identified by DNA next-generation sequencing (NGS), but the role of exonic breakpoints remains elusive. We investigated whether exonic-breakpoint fusions could predict matched targeted therapy efficacy in non-small cell lung cancer (NSCLC).

Methods

NSCLC samples were analyzed by DNA NGS, RNA NGS, immunohistochemistry (IHC), and fluorescence in situ hybridization.

Results

Using DNA NGS, kinase fusions were identified in 685 of 7148 (9.6%) NSCLCs, with 74 harboring exonic-breakpoint fusions, mostly anaplastic lymphoma kinase (ALK) fusions. RNA NGS and IHC revealed that 11 of 55 (20%) exonic-breakpoint fusions generated no aberrant transcript/protein, possibly due to open reading frame disruption or different gene transcriptional orientations. Four cases of genomic-positive but RNA/protein-negative fusions were treated with matched targeted therapy, but progressive disease developed within 2 months. Nevertheless, 44 of 55 (80%) exonic-breakpoint fusions produced chimeric transcripts/proteins, possibly owing to various alternative splicing patterns, including exon skipping, alternative splice site selection, and intron retention. Most of these genomic- and RNA/protein-positive fusion cases showed a clinical response to matched targeted therapy. Particularly, there were no differences in objective response rate (P = 0.714) or median progression-free survival (P = 0.500) between intronic-breakpoint (n = 56) and exonic-breakpoint ALK fusion subtypes (n = 11) among ALK RNA/protein-validated patients who received first-line crizotinib.

Conclusions

Exonic-breakpoint fusions may generate in-frame fusion transcripts/proteins or not, and thus are unreliable for predicting the efficacy of targeted therapy, which highlights the necessity of implementing RNA or protein assays for functional validation in exonic-breakpoint fusion cases.
Molecular cloning, characterization, and functional analysis of the uncharacterized C11orf96 gene
Authors: Yang Hongzao , Zhu Jie , Guo Hongyuan , Tang Aoxing , Chen Shaoyu , Zhang Da , Yuan Ligang , Liu Guangqing
Published: May 2022

Background

The mammalian genome encodes millions of proteins. Although many proteins have been discovered and identified, a large part of proteins encoded by genes are yet to be discovered or fully characterized. In the present study, we successfully identified a host protein C11orf96 that was significantly upregulated after viral infection.

Results

First, we successfully cloned the coding sequence (CDS) region of the cat, human, and mouse C11orf96 gene. The CDS region of the C11orf96 gene is 372 bp long, encodes 124 amino acids, and is relatively conserved in different mammals. From bioinformatics analysis, we found that C11orf96 is rich in Ser and has multiple predicted phosphorylation sites. Moreover, protein interaction prediction analysis revealed that the protein is associated with several transmembrane family proteins and zinc finger proteins. Subsequently, we found that C11orf96 is strictly distributed in the cytoplasm. According to the tissue distribution characteristics, C11orf96 is distributed in all tissues and organs, with the highest expression levels in the kidney. These results indicate that C11orf96 may play a specific biological role in the kidney.

Conclusions

Summarizing, these data lay the foundation for studying the biological functions of C11orf96 and for exploring its role in viral replication.
The ultrasound-guided funicular block in cats undergoing orchiectomy: ropivacaine injection into the spermatic cord to improve intra and postoperative analgesia
Authors: Cicirelli Vincenzo , Matteo Burgio , Di Bella Caterina , Lacalandra Giovanni Michele , Aiudi Giulio
Published: May 2022

Background

The orchiectomy in cats is a common surgical procedure with medium level of pain and for this reason requires intra and postoperative analgesia management. The aim of this study was to compare intra and postoperative pain in two groups of cats undergoing orchiectomy. Sixty healthy cats were randomly assigned in two groups (n = 30) to receive pre surgery ropivacaine hydrochloride (0.2 mL/kg at 0.5%) (R Group) or NaCl 0.9% (C group) into the spermatic cord. The intraoperative evaluation was carried out using the cardiorespiratory stability parameters and eventually administration of rescue analgesia. A rescue analgesia (fentanyl 2 µg/kg) was administered during orchiectomy in case of considerable increase of blood pressure, heart rate or respiratory rate. The postoperative evaluation was been done using scores following a UNESP-Botucatu multimodal scale for 6 h post-surgery.

Results

As result, cats in R group responded better to surgical procedure, maintaining lower postoperative pain scores than C group.

Conclusions

The ultrasound-guided funicular block used in this study, as already demonstrated in dogs, is a good method to protect the cats from surgical pain and ensure a good level of surgical analgesia.
De novo biosynthesis of p-coumaric acid and caffeic acid from carboxymethyl-cellulose by microbial co-culture strategy
Authors: Cai Miao , Liu Jiayu , Song Xiaofei , Qi Hang , Li Yuanzi , Wu Zhenzhou , Xu Haijin , Qiao Mingqiang
Published: May 2022

Background

Aromatic compounds, such as p-coumaric acid (p-CA) and caffeic acid, are secondary metabolites of various plants, and are widely used in diet and industry for their biological activities. In addition to expensive and unsustainable methods of plant extraction and chemical synthesis, the strategy for heterologous synthesis of aromatic compounds in microorganisms has received much attention. As the most abundant renewable resource in the world, lignocellulose is an economical and environmentally friendly alternative to edible, high-cost carbon sources such as glucose.

Results

In the present study, carboxymethyl-cellulose (CMC) was utilized as the sole carbon source, and a metabolically engineered Saccharomyces cerevisiae strain SK10-3 was co-cultured with other recombinant S. cerevisiae strains to achieve the bioconversion of value-added products from CMC. By optimizing the inoculation ratio, interval time, and carbon source content, the final titer of p-CA in 30 g/L CMC medium was increased to 71.71 mg/L, which was 155.9-fold higher than that achieved in mono-culture. The de novo biosynthesis of caffeic acid in the CMC medium was also achieved through a three-strain co-cultivation. Caffeic acid production was up to 16.91 mg/L after optimizing the inoculation ratio of these strains.

Conclusion

De novo biosynthesis of p-CA and caffeic acid from lignocellulose through a co-cultivation strategy was achieved for the first time. This study provides favorable support for the biosynthesis of more high value-added products from economical substrates. In addition, the multi-strain co-culture strategy can effectively improve the final titer of the target products, which has high application potential in the field of industrial production.
Dairy food intake is not associated with spinal trabecular bone score in men and women: the Framingham Osteoporosis Study
Authors: Millar Courtney L. , Kiel Douglas P. , Hannan Marian T. , Sahni Shivani
Published: May 2022

Background

Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone texture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt and milk + yogurt + cheese) with spinal trabecular bone score (TBS).

Methods

In this cross-sectional study, a validated semi-quantitative food frequency questionnaire was used to assess dairy food intake (servings/wk). TBS, an analysis of bone texture, was calculated from dual energy X-ray absorptiometry (DXA) scans. Sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted via residual methods) with each bone measure adjusting for covariates.

Results

Mean age of 4,740 participants was 49 (SD: 13) years and mean milk + yogurt + cheese intake was 10.1 (SD: 8.4) servings/week in men and 10.9 (SD: 8.0) servings/week in women. There were no associations between dairy food intake and spinal TBS in adjusted models.

Conclusions

In this cohort of primarily healthy adults, dairy intake was not associated with bone texture.
A multimodal analytical method to simultaneously determine monoacetyldiacylglycerols, medium and long chain triglycerides in biological samples during routine lipidomics
Authors: Manful Charles F. , Pham Thu H. , Spicer Heather , Thomas Raymond H.
Published: May 2022

Background

Monoacetyldiglycerides (MAcDG), are acetylated triglycerides (TG) and an emerging class of bioactive or functional lipid with promising nutritional, medical, and industrial applications. A major challenge exists when analyzing MAcDG from other subclasses of TG in biological matrices, limiting knowledge on their applications and metabolism.

Methods

Herein a multimodal analytical method for resolution, identification, and quantitation of MAcDG in biological samples was demonstrated based on thin layer chromatography-flame ionization detection complimentary with C30-reversed phase liquid chromatography-high resolution accurate mass tandem mass spectrometry. This method was then applied to determine the MAcDG molecular species composition and quantity in E. solidaginis larvae. The statistical method for analysis of TG subclass composition and molecular species composition of E. solidaginis larvae was one-way analysis of variance (ANOVA).

Results

The findings suggest that the proposed analytical method could simultaneously provide a fast, accurate, sensitive, high throughput analysis of MAcDG from other TG subclasses, including the fatty acids, isomers, and molecular species composition.

Conclusion

This method would allow for MAcDG to be included during routine lipidomics analysis of biological samples and will have broad interests and applications in the scientific community in areas such as nutrition, climate change, medicine and biofuel innovations.

Graphical abstract
The impact of body mass index on short-term and long-term surgical outcomes of laparoscopic hepatectomy in liver carcinoma patients: a retrospective study
Authors: Zhao Lei , Wang Jiangang , Kong Jingxia , Zheng Xing , Yu Xin
Published: May 2022

Background

It was generally accepted that obesity could increase the morbidity and mortality of surgical patients. However, the influence of body mass index (BMI) on short-term and long-term surgical outcomes of laparoscopic hepatectomy (LH) for patients with liver carcinoma remains unclear. The aim of this study was to evaluate the influence of BMI on surgical outcomes.

Methods

From August 2003 to April 2016, 201 patients with liver carcinoma who underwent LH were enrolled in our study. Based on their BMI in line with the WHO’s definition of obesity for the Asia-Pacific region, patients were divided into three groups: underweight (BMI< 18.5 kg/m2), normal weight (18.5≤BMI< 23 kg/m2), and overweight (BMI≥ 23 kg/m2). Demographics and surgical outcomes of laparoscopic hepatectomy were compared in different BMI stratification. We investigated overall survival and relapse-free survival across the BMI categories.

Results

Of the 201 patients, 23 (11.44%) were underweight, 96 (47.76%) were normal weight, and 82 (40.80%) were overweight. The overall complication rate in the underweight group was much higher than that in the normal weight and overweight groups (p=0.048). Postoperative complications, underweight patients developed grade III or higher Clavien-Dindo classifications (p=0.042). Among the three BMI groups, there were no significant differences in overall and relapse-free survival with Kaplan-Meier analysis (p=0.104 and p=0.190, respectively). On the other hand, gender, age, liver cirrhosis, bile leak, ascites, and Clavien classification (III-IV) were not independent risk factors for overall and relapse-free survival in multivariable Cox proportional hazards models.

Conclusions

BMI status does not affect patients with liver carcinoma long-term surgical outcomes concerned to overall survival and relapse-free survival after laparoscopic hepatectomy. However, being underweight was associated with an increased perioperative complication rate, and perioperative careful monitoring might be required after hepatectomy for underweight with liver carcinoma.
The “Great Debate” at Melanoma Bridge 2021, December 2nd–4th, 2021
Authors: Ascierto Paolo A. , Warner Allison Betof , Blank Christian , Caracò Corrado , Demaria Sandra , Gershenwald Jeffrey E. , Khushalani Nikhil I. , Long Georgina V. , Luke Jason J. , Mehnert Janice M. , Robert Caroline , Rutkowski Piotr , Tawbi Hussein A. , Osman Iman , Puzanov Igor
Published: May 2022

The Great Debate session at the 2021 Melanoma Bridge virtual congress (December 2–4) featured counterpoint views from experts on seven important issues in melanoma. The debates considered the use of adoptive cell therapy versus use of bispecific antibodies, mitogen-activated protein kinase (MAPK) inhibitors versus immunotherapy in the adjuvant setting, whether the use of corticosteroids for the management of side effects have an impact on outcomes, the choice of programmed death (PD)-1 combination therapy with cytotoxic T-lymphocyte-associated antigen (CTLA)-4 or lymphocyte-activation gene (LAG)-3, whether radiation is needed for brain metastases, when lymphadenectomy should be integrated into the treatment plan and then the last debate, telemedicine versus face-to-face. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. Audiences voted both before and after each debate.
Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study
Authors: Husain-Syed Faeq , Emlet David R. , Wilhelm Jochen , Danesi Tommaso Hinna , Ferrari Fiorenza , Bezerra Pércia , Lopez-Giacoman Salvador , Villa Gianluca , Tello Khodr , Birk Horst-Walter , Seeger Werner , Giavarina Davide , Salvador Loris , Fuhrman Dana Y. , Kellum John A. , Ronco Claudio ,   the IRRIV-AKI Study Group, Caprara Carlotta , Corradi Valentina , Cal Massimo , Estremadoyro Carla , Lu Renhua , Samoni Sara , Sharma Aashish , Tofani Lorenzo , Virzì Grazia Maria
Published: May 2022

Background

Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects.

Methods

The prospective “Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation” study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations.

Results

The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI − 1.4, − 1.7] vs. − 3.3 [95% CI − 4.4, − 2.2] ml/min/1.73 m2) and 12 months (− 2.7 [95% CI − 4.2, − 1.2] vs − 10.2 [95% CI − 11.3, − 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (− 8.0 [95% CI − 14.1, − 1.9] vs. − 18.6 [95% CI − 23.3, − 14.0] ml/min/1.73 m2; p = 0.008). A dose–response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression.

Conclusions

A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells.

Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).
Aluminium oxide nanoparticles compromise spatial memory performance and proBDNF-mediated neuronal function in the hippocampus of rats
Authors: Sun Wei , Li Jia , Li Xiaoliang , Chen Xiao , Mei Yazi , Yang Yang , An Lei
Published: May 2022

Background

Alumina nanoparticles (aluminaNPs), which are widely used in a range of daily and medical fields, have been shown to penetrate blood-brain barrier, and distribute and accumulate in different brain areas. Although oral treatment of aluminaNPs induces hippocampus-dependent learning and memory impairments, characteristic effects and exact mechanisms have not been fully elucidated. Here, male adult rats received a single bilateral infusion of aluminaNPs (10 or 20 µg/kg of body weight) into the hippocampal region, and their behavioral performance and neural function were assessed.

Results

The results indicated that the intra-hippocampus infusions at both doses of aluminaNPs did not cause spatial learning inability but memory deficit in the water maze task. This impairment was attributed to the effects of aluminaNP on memory consolidation phase through activation of proBDNF/RhoA pathway. Inhibition of the increased proBDNF by hippocampal infusions of p75NTRantagonist could effectively rescue the memory impairment. Incubation of aluminaNPs exaggerated GluN2B-dependent LTD induction with no effects on LTD expression in hippocampal slices. AluminaNP could also depress the amplitude of NMDA-GluN2B EPSCs. Meanwhile, increased reactive oxygen specie production was reduced by blocking proBDNF-p75NTRpathway in the hippocampal homogenates. Furthermore, the neuronal correlate of memory behavior was drastically weakened in the aluminaNP-infused groups. The dysfunction of synaptic and neuronal could be obviously mitigated by blocking proBDNF receptor p75NTR, implying the involvement of proBDNF signaling in aluminaNP-impaired memory process.

Conclusions

Taken together, our findings provide the first evidence that the accumulation of aluminaNPs in the hippocampus exaggeratedly activates proBDNF signaling, which leads to neural and memory impairments.
A novel protein encoded by ZCRB1-induced circHEATR5B suppresses aerobic glycolysis of GBM through phosphorylation of JMJD5
Authors: Song Jian , Zheng Jian , Liu Xiaobai , Dong Weiwei , Yang Chunqing , Wang Di , Ruan Xuelei , Zhao Yubo , Liu Libo , Wang Ping , Zhang Mengyang , Liu Yunhui
Published: May 2022

Background

RNA-binding proteins (RBPs) and circular RNAs (circRNAs) play important roles in glioblastoma multiforme (GBM). Aerobic glycolysis is a metabolic characteristic of GBM. However, the roles of RBPs and circRNAs in aerobic glycolysis in GBM remain unclear. The aim of this study is to explore the mechanisms by which RBPs and circRNAs regulate aerobic glycolysis in GBM cells.

Methods

RNA sequencing and circRNA microarray analysis were performed to identify RBPs and circRNAs for further study. Mass spectrometry validated the encoded protein and its interacting proteins. Quantitative reverse transcription PCR and western blot assays were used to determine the mRNA and protein expression, respectively. Furthermore, immunofluorescence and fluorescence in situ hybridization assays were used to determine the protein and RNA localization, respectively. Glucose and lactate measurement assays, Seahorse XF glycolysis stress assays and cell viability assays were conducted to investigate the effects on glycolysis and proliferation in GBM cells.

Results

We selected zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1) and circRNA HEAT repeat containing 5B (circHEATR5B) as candidates for this study. These genes were expressed at low levels in GBM tissues and cells. Both ZCRB1 and circHEATR5B overexpression suppressed aerobic glycolysis and proliferation in GBM cells. ZCRB1 overexpression promoted the Alu element-mediated formation of circHEATR5B. In addition, circHEATR5B encoded a novel protein HEATR5B-881aa which interacted directly with Jumonji C-domain-containing 5 (JMJD5) and reduced its stability by phosphorylating S361. JMJD5 knockdown increased pyruvate kinase M2 (PKM2) enzymatic activity and suppressed glycolysis and proliferation in GBM cells. Finally, ZCRB1, circHEATR5B and HEATR5B-881aa overexpression inhibited GBM xenograft growth and prolonged the survival time of nude mice.

Conclusions

This study reveals a novel mechanism of regulating aerobic glycolysis and proliferation in GBM cells through the ZCRB1/circHEATR5B/HEATR5B-881aa/JMJD5/PKM2 pathway, which can provide novel strategies and potential targets for GBM therapy.
Acute glycemic variability and mortality of patients with acute stroke: a meta-analysis
Authors: Lin Jinbo , Cai Chunsheng , Xie Yituan , Yi Li
Published: May 2022

Background

Increased glucose fluctuation has been related to poor prognosis in patients with critical illnesses, while its prognostic role in patients with acute stroke remains unknown. The meta-analysis aimed to evaluate the association between the acute glycemic variation (GV) and mortality risk in patients with acute stroke.

Methods

Cohort studies were obtained by searching Medline, Web of Science, Embase, Wanfang and CNKI databases. A random-effect model which incorporates the intra-study heterogeneity was chosen to pool the results.

Results

Ten cohort studies with 1433 patients were included, and 280 (19.5%) of them died within 90 days of disease onset. Results of the meta-analyses showed that a higher acute GV was associated with an increased risk of early mortality in patients with acute stroke, as indicated by GV measured with the coefficient of variation of blood glucose (CVBG, odds ratio [OR]: 2.24, 95% CI 1.40 to 3.58, p < 0.001, I2 = 73%), the standard deviation of blood glucose (SDBG, OR: 2.31, 95% CI 1.70 to 3.13, p < 0.001, I2 = 50%), and the mean amplitude of glycemic excursion (OR: 3.57, 95% CI 1.44 to 8.85, p = 0.006, I2 = 23%). For acute GV measured with CVBG and SDBG, subgroup analyses showed consistent results in patients with acute ischemic and hemorrhagic stroke, and for studies reporting 28-day and 90-day all-cause mortality (p for subgroup analysis all > 0.05).

Conclusions

Higher acute GV may be an independent risk factor of early mortality in patients with acute stroke.
FirmiData: a set of 40 genomes of Firmicutes with a curated annotation of ICEs and IMEs
Authors: Guédon Gérard , Lao Julie , Payot Sophie , Lacroix Thomas , Chiapello Hélène , Leblond-Bourget Nathalie
Published: May 2022

Objectives

‘Integrative and Conjugative Elements’ (ICEs) and ‘Integrative and Mobilizable Elements’ (IMEs) are two classes of mobile genetic elements that are complex to detect and delineate. Therefore, they are yet poorly annotated in bacterial genomes. FirmiData provides to the scientific community of microbiologists and bioinformaticians a reference resource of annotated ICEs and of IMEs from Firmicutes. It illustrates their prevalence and their diversity but also gives information on their organization.

FirmiData was designed to assist the scientific community in identifying and annotating these elements by using the sequences of these ICEs and IMEs for the identification of related elements in other genomes of Firmicutes. Therefore, Firmidata meets the needs of the scientific community.

Data description

Firmidata provides a manually curated annotation of 98 ICEs and 148 IMEs identified in 40 chromosomes of Firmicutes. The delineation at the nucleotide level of almost all of these elements allows for the characterization of the genes they carry.
Brazilian spatial, demographic, and socioeconomic data from 1996 to 2020
Authors: Fernandes Santos Alves Ronaldo , de Moraes Mello Boccolini Patricia , Baroni Lais Ribeiro , de Almeida Relvas-Brandt Laís , de Abreu Junqueira Gritz Raquel , Siqueira Boccolini Cristiano
Published: May 2022

Objectives

We present a database on Brazilian spatial, demographic, and socioeconomic characteristics from 1996 to 2020. This database aims for integration and harmonization with epidemiological data from two major studies. It can also be a valuable database for designing and conducting various types of epidemiologic research, such as health inequality studies, ecological studies (mapping and time-trends), and multi-level analysis.

Data description

The database gathers official information obtained via open sources from the Brazilian Institute of Geography and Statistics, the Institute for Applied Economic Research, and the Ministry of Health. It includes 139,153 observations and 26 attributes aggregated by years and policy-relevant geographic units on geocoding of municipality centroids, total population size, child population by age-group, birth and mortality measures, Brazilian Municipal Human Development Index, Gini coefficient, Gross Domestic Product, and sanitation. We automated all data processing and curation in the free and open software R.
DNA methylation analysis of tumor suppressor genes in liquid biopsy components of early stage NSCLC: a promising tool for early detection
Authors: Markou Α. , Londra D. , Tserpeli V. , Kollias Ι. , Tsaroucha E. , Vamvakaris I. , Potaris K. , Pateras I. , Kotsakis Α. , Georgoulias V. , Lianidou Ε.
Published: May 2022

Purpose

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) analysis represents a liquid biopsy approach for real-time monitoring of tumor evolution. DNA methylation is considered to be an early event in the process of cancer development and progression. The aim of the present study was to evaluate whether detection of DNA methylation of selected tumor suppressor genes in CTC and matched ctDNA provides prognostic information in early stage NSCLC.

Experimental design

The methylation status of five selected gene promoters (APC, RASSFIA1, FOXA1, SLFN11, SHOX2) was examined by highly specific and sensitive real-time methylation specific PCR assays in: (a) a training group of 35 primary tumors and their corresponding adjacent non-cancerous tissues of early stage NSCLC patients, (b) a validation group of 22 primary tumor tissues (FFPEs) and 42 peripheral blood samples of early stage NSCLC patients. gDNA was isolated from FFPEs, CTCs (size-based enriched by Parsortix; Angle and plasma, and (c) a control group of healthy blood donors (n = 12).

Results

All five gene promoters tested were highly methylated in the training group; methylation of SHOX2 promoter in primary tumors was associated with unfavorable outcome. RASSFIA and APC were found methylated in plasma-cfDNA samples at 14.3% and 11.9%, respectively, whereas in the corresponding CTCs SLFN11 and APC promoters were methylated in 7.1%. The incidence of relapses was higher in patients with a) promoter methylation of APC and SLFN11 in plasma-cfDNA (P = 0.037 and P = 0.042 respectively) and b) at least one detected methylated gene promoter in CTC or plasma-cfDNA (P = 0.015).

Conclusions

DNA methylation of these five gene promoters was significantly lower in CTCs and plasma-cfDNA than in the primary tumors. Combination of DNA methylation analysis in CTC and plasma-cfDNA was associated with worse DFI of NSCLC patients. Additional studies are required to validate our findings in a large cohort of early stage NSCLC patients.
Considerations for artificial intelligence clinical impact in oncologic imaging: an AI4HI position paper
Authors: Marti-Bonmati Luis , Koh Dow-Mu , Riklund Katrine , Bobowicz Maciej , Roussakis Yiannis , Vilanova Joan C. , Fütterer Jurgen J. , Rimola Jordi , Mallol Pedro , Ribas Gloria , Miguel Ana , Tsiknakis Manolis , Lekadir Karim , Tsakou Gianna
Published: May 2022

To achieve clinical impact in daily oncological practice, emerging AI-based cancer imaging research needs to have clearly defined medical focus, AI methods, and outcomes to be estimated. AI-supported cancer imaging should predict major relevant clinical endpoints, aiming to extract associations and draw inferences in a fair, robust, and trustworthy way. AI-assisted solutions as medical devices, developed using multicenter heterogeneous datasets, should be targeted to have an impact on the clinical care pathway. When designing an AI-based research study in oncologic imaging, ensuring clinical impact in AI solutions requires careful consideration of key aspects, including target population selection, sample size definition, standards, and common data elements utilization, balanced dataset splitting, appropriate validation methodology, adequate ground truth, and careful selection of clinical endpoints. Endpoints may be pathology hallmarks, disease behavior, treatment response, or patient prognosis. Ensuring ethical, safety, and privacy considerations are also mandatory before clinical validation is performed. The Artificial Intelligence for Health Imaging (AI4HI) Clinical Working Group has discussed and present in this paper some indicative Machine Learning (ML) enabled decision-support solutions currently under research in the AI4HI projects, as well as the main considerations and requirements that AI solutions should have from a clinical perspective, which can be adopted into clinical practice. If effectively designed, implemented, and validated, cancer imaging AI-supported tools will have the potential to revolutionize the field of precision medicine in oncology.
Diabetic foot infections: how to investigate more efficiently? A retrospective study in a quaternary university center
Authors: Ibrahim Aisin , Berkache Moncef , Morency-Potvin Philippe , Juneau Daniel , Koenig Martial , Bourduas Karine , Freire Véronique
Published: May 2022

Background

Diabetic foot infections are frequent and associated with substantial morbidity and substantial cost to the healthcare system. Up to 34% of diabetic patients will develop an ulcer potentially leading to osteomyelitis. Imaging plays a crucial role in the diagnostic process. Imaging modalities to investigate the diabetic foot infection are many and imaging prescription habits remain heterogeneous across physicians. We aimed to improve the appropriateness of imaging examination requested, and performed, for diabetic foot osteomyelitis and we aimed to reduce the overall imaging-related cost.

Methods

Local committee was created to develop an algorithm for suspected diabetic foot osteomyelitis. Best practices were defined by the local algorithm. The algorithm was shared with our physicians. Pre- and post-intervention analysis was conducted retrospectively. All adult diabetic patients with suspected foot osteomyelitis were included. Adherence to best practices was measured. Statistical analysis with Chi-Square and two tailed unpaired t-test was performed.

Results

Pre-intervention cohort had 223 patients (mean age: 63; 168 men). Adherence to best practice was 43%. Scintigraphy (48%) preferred over MRI (44%) and performed simultaneously in 15 patients. Post-intervention cohort had 73 patients (mean age: 66; 62 men). Adherence to best practice was 78%, improved by 35% (p < 0.001). MRI (51%) preferred over scintigraphy (23%) and performed simultaneously in three patients. Scintigraphy examinations decreased by 25% (p < 0.001). MRI examinations increased by 7% (p = 0.32). Hospital imaging related fees decreased by 22% per patient (p = 0.002).

Conclusion

Interval improvement in adequate adherence while reducing unnecessary examinations for patients and decreasing costs for the healthcare system was observed.
Existence and multiplicity of nontrivial solutions for poly-Laplacian systems on finite graphs
Authors: Zhang Xuechen , Zhang Xingyong , Xie Junping , Yu Xiaoli
Published: May 2022

In this paper, we investigate the existence and multiplicity of nontrivial solutions for poly-Laplacian system on a finite graph $G=(V, E)$
G
=
(
V
,
E
)
, which is a generalization of the Yamabe equation on a finite graph. When the nonlinear term F satisfies the super-$(p, q)$
(
p
,
q
)
-linear growth condition, by using the mountain pass theorem we obtain that the system has at least one nontrivial solution, and by using the symmetric mountain pass theorem, we obtain that the system has at least dim W nontrivial solutions, where W is the working space of the poly-Laplacian system. We also obtain the corresponding result for the poly-Laplacian equation. In some sense, our results improve some results in (Grigor’yan et al. in J. Differ. Equ. 261(9):4924–4943, 2016).
Novel Chloroflexi genomes from the deepest ocean reveal metabolic strategies for the adaptation to deep-sea habitats
Authors: Liu Rulong , Wei Xing , Song Weizhi , Wang Li , Cao Junwei , Wu Jiaxin , Thomas Torsten , Jin Tao , Wang Zixuan , Wei Wenxia , Wei Yuli , Zhai Haofeng , Yao Cheng , Shen Ziyi , Du Jiangtao , Fang Jiasong
Published: May 2022

Background

The deep sea harbors the majority of the microbial biomass in the ocean and is a key site for organic matter (OM) remineralization and storage in the biosphere. Microbial metabolism in the deep ocean is greatly controlled by the generally depleted but periodically fluctuating supply of OM. Currently, little is known about metabolic potentials of dominant deep-sea microbes to cope with the variable OM inputs, especially for those living in the hadal trenches—the deepest part of the ocean.

Results

In this study, we report the first extensive examination of the metabolic potentials of hadal sedimentChloroflexi, a dominant phylum in hadal trenches and the global deep ocean. In total, 62 metagenome-assembled-genomes (MAGs) were reconstructed from nine metagenomic datasets derived from sediments of the Mariana Trench. These MAGs represent six novel species, four novel genera, one novel family, and one novel order within the classesAnaerolineaeandDehalococcoidia. Fragment recruitment showed that these MAGs are globally distributed in deep-sea waters and surface sediments, and transcriptomic analysis indicated their in situ activities. Metabolic reconstruction showed that hadalChlorofleximainly had a heterotrophic lifestyle, with the potential to degrade a wide range of organic carbon, sulfur, and halogenated compounds. Our results revealed for the first time that hadalChloroflexiharbor pathways for the complete hydrolytic or oxidative degradation of various recalcitrant OM, including aromatic compounds (e.g., benzoate), polyaromatic hydrocarbons (e.g., fluorene), polychlorobiphenyl (e.g., 4-chlorobiphenyl), and organochlorine compounds (e.g., chloroalkanes, chlorocyclohexane). Moreover, these organisms showed the potential to synthesize energy storage compounds (e.g., trehalose) and had regulatory modules to respond to changes in nutrient conditions. These metabolic traits suggest thatChlorofleximay follow a “feast-or-famine” metabolic strategy, i.e., preferentially consume labile OM and store the energy intracellularly under OM-rich conditions, and utilize the stored energy or degrade recalcitrant OM for survival under OM-limited condition.

Conclusion

This study expands the current knowledge on metabolic strategies in deep-oceanChlorolfexiand highlights their significance in deep-sea carbon, sulfur, and halogen cycles. The metabolic plasticity likely providesChloroflexiwith advantages for survival under variable and heterogenic OM inputs in the deep ocean.
Impact of pharmacist services on economic, clinical, and humanistic outcome (ECHO) of South Asian patients: a systematic review
Authors: Shrestha Sunil , Shrestha Rajeev , Ahmed Ali , Sapkota Binaya , Khatiwada Asmita Priyadarshini , Christopher Christina Malini , Thapa Parbati , KC Bhuvan , Blebil Ali Qais , Khanal Saval , Paudyal Vibhu
Published: May 2022

Background

Pharmacists in high-income countries routinely provide efficient pharmacy or pharmaceutical care services that are known to improve clinical, economic, and humanistic outcomes (ECHO) of patients. However, pharmacy services in low- and middle-income countries, mainly South Asia, are still evolving and limited to providing traditional pharmacy services such as dispensing prescription medicines. This systematic review aims to assess and evaluate the impact of pharmacists’ services on the ECHO of patients in South Asian countries.

Methods

We searched PubMed/Medline, Scopus, EMBASE, CINAHL, and Cochrane Library for relevant articles published from inception to 20th September 2021. Original studies (only randomised controlled trials) conducted in South Asian countries (published only in the English language) and investigating the economic, clinical (therapeutic and medication safety), and humanistic impact (health-related quality of life) of pharmacists’ services, from both hospital and community settings, were included.

Results

The electronic search yielded 430 studies, of which 20 relevant ones were included in this review. Most studies were conducted in India (9/20), followed by Pakistan (6/20), Nepal (4/20) and Sri Lanka (1/20). One study showed a low risk of bias (RoB), 12 studies showed some concern, and seven studies showed a high RoB. Follow-up duration ranged from 2 to 36 months. Therapeutic outcomes such as HbA1c value and blood pressure (systolic blood pressure and diastolic blood pressure) studied in fourteen studies were found to be reduced. Seventeen studies reported humanistic outcomes such as medication adherence, knowledge and health-related quality of life, which were found to be improved. One study reported safety and economic outcomes each. Most interventions delivered by the pharmacists were related to education and counselling of patients including disease monitoring, treatment optimisation, medication adherence, diet, nutrition, and lifestyle.

Conclusion

This systematic review suggests that pharmacists have essential roles in improving patients’ ECHO in South Asian countries via patient education and counselling; however, further rigorous studies with appropriate study design with proper randomisation of intervention and control groups are anticipated.
Jejunogastric intussusception after pancreaticoduodenectomy: a case report
Authors: Yogo Konosuke , Sando Masanori , Kobayashi Ryutaro , Yano Genta , Ohara Noriaki , Kawai Kiyotaka , Takagi Kenji , Kawai Satoru , Kamiya Satoaki
Published: May 2022

Background

Jejunogastric intussusception (JGI) is a rare, but potentially fatal complication that can occur following gastric surgery, and the reported incidence of JGI is as low as 0.1%. Early diagnosis and treatment are critical for JGI to prevent major complications such as bowel necrosis and death. Although emergency surgery is the standard treatment, endoscopic reduction has also been reported to be effective in JGI patients without bowel necrosis. Several early recurrent cases treated with surgical or endoscopic reduction have been reported. We report an extremely rare case of JGI after pancreaticoduodenectomy (PD) using Child’s procedure that was successfully treated with surgical reduction and fixation.

Case presentation

An 81-year-old man who had undergone PD using Child’s procedure 3 years ago presented to our hospital with epigastric pain and nausea. His vital signs were stable, and abdominal examination revealed mild tenderness with a palpable mass in the mid-epigastrium. Abdominal computed tomography (CT) and gastroscopy revealed a JGI of the efferent loop, and exploratory laparotomy was immediately performed. During the operation, the efferent loop showed no adhesions and was intussuscepted through the gastrojejunostomy into the gastric lumen. An incision in the anterior wall of the stomach revealed no evidence of ischemia of the intussusceptum. The efferent loop was reduced using Hutchinson’s maneuver and fixed to the afferent loop to prevent a recurrence. The postoperative course was uneventful, and there was no sign of recurrence 12 months postoperatively.

Conclusions

JGI after PD is an extremely rare, but has severe complications. Surgery might be the optimal treatment for JGI in terms of preventing recurrence, even in cases without bowel necrosis.
Tone of language, financial disclosure, and earnings management: a textual analysis of form 20-F
Authors: Li Shuangyan , Wang Guangrui , Luo Yongli
Published: May 2022

This study investigates the relationship between the tone of financial disclosures and managers’ earnings management behavior using Form 20-F filings of Chinese firms listed in the U.S. during 2002–2014. The results show that the proportion of positive, uncertain, or modal words used in financial disclosures is positively related to corporate earnings management, implying that managers attempt to conceal earnings management behavior by manipulating the tone of their financial reports. In addition, robustness tests are conducted using an alternative proxy for earnings management that considers the effects of the financial crisis and separately examines the information and non-information technology industries. The results suggest that the tone used in financial disclosures has informative value, and textual analysis can be an effective tool for identifying earnings management.