bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel prognostic biomarker in progression free survival for patients with cervical cancer, glucose to c-reactive protein ratio (GCR)
Authors: Buyukbayram Mehmet Emin , Hannarici Zekeriya , Turhan Aykut , Caglar Alperen Akansel , Esdur Pınar Çoban , Bilici Mehmet , Tekin Salim Basol , Erdemci Burak
Published: May 2024

Background

Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer.

Methods

We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined.

Results

Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001).

Conclusion

In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration.
Mesenteric and omental lymphatic malformations in children: seven-year surgical experience from two centers in China
Authors: Yan Jiayu , Fu Yao , Liu Shuting , Bai Yuzuo , Chen Yajun
Published: May 2024

Purpose

To compare the clinical characteristics, surgical management and prognosis of mesenteric lymphatic malformations (ML) and omental lymphatic malformations (OL) in children.

Methods

This retrospective study included 148 ML patients and 53 OL patients who underwent surgical treatment at two centers between January 2016 and December 2022. Details about the patients’ clinical characteristics, cyst characteristics, preoperative complications, surgical methods, and prognosis were retrieved and compared.

Results

No significant differences in sex ratio, prenatal diagnosis, or age of diagnosis were noted between ML and OL patients. Vomiting was more common in ML patients than in OL patients (46.6% vs. 22.6%, P = 0.002), but OL patients were more likely to be misdiagnosed (35.8% vs. 18.9%, P = 0.012). The size of the cysts in OL patients was significantly larger than that in ML patients (14.0 [4.0–30.0] vs. 10.0 [2.0–50.0] cm, P<0.001), and cysts with turbid fluid were more common in OL patients (38.0% vs. 20.6%, P<0.001). More OL patients than ML patients had preoperative hemorrhage or infection of cysts (41.5% vs. 31.8%, P<0.016). Cyst excision was performed in 137 (92.6%) ML patients and 51 (96.2%) OL patients, and the incidence of postoperative complications was lower (12.6% vs. 4.2%, P = 0.165) among OL patients. The main postoperative complications included adhesive ileus and recurrence of cysts. Additionally, more OL patients than ML patients were treated with laparoscopic surgery (69.8% vs. 39.2%, P<0.001).

Conclusions

There were differences in clinical characteristics, cyst characteristics and preoperative complications between ML and OL patients. Cyst excision was the most common surgical method that was used to treat both ML and OL patients, and laparoscopic surgery could be a feasible surgical approach for treating OL patients with a good prognosis.

Trial registration

Retrospectively registered.
Prevalence and factors associated with rotavirus diarrhea among children aged 3–24 months after the introduction of the vaccine at a referral hospital in Uganda: a cross-sectional study
Authors: Laker Goretty , Nankunda Jolly , Melvis Bernis Maren , Kajoba Dickson , Nduwimana Martin , Kimera Joel , Odong Richard Justine , Edyedu Isaac
Published: May 2024

Background

Rotavirus has a significant morbidity and mortality in children under two years. The burden of rotavirus diarrhea 4 years post introduction of rotavirus vaccine in Uganda is not well established. This study aimed to determine the prevalence, severity of dehydration and factors associated with rotavirus diarrhea among children aged 3 to 24 months after the introduction of the vaccine at Fort Portal Regional Referral hospital.

Methods

This was a cross-sectional hospital-based study in which children with acute watery diarrhea were included. A rectal tube was used to collect a stool sample for those unable to provide samples. Stool was tested for rotavirus using rapid immunochromatographic assay. Data was analysed using SPSS version 22 with logistic regression done to determine the factors.

Results

Out of 268 children with acute watery diarrhea, 133 (49.6%) were females. Rotavirus test was positive in 42 (15.7%), majority of whom had some dehydration 28(66.7%). The factors that were independently associated with rotavirus diarrhea were; age < 12 months (AOR = 8.87, P = 0.014), male gender (AOR = 0.08, P = 0.001), coming from a home with another person with diarrhea (AOR = 17.82, P = 0.001) or a home where the water source was a well (AOR = 50.17, P = 0.002).

Conclusion

The prevalence of rotavirus diarrhea was three times less in the post rotavirus vaccination period compared to pre-rota vaccination period. Majority of the participants with rotavirus diarrhea had some dehydration. There is need for provision of safe water sources to all homes. Surveillance to determine the cause of the non rota diarrhea should be done.
Family cohesion and quality of life significantly affecting personality changes in adult epilepsy patients: a case-control study
Authors: Li Jiaai , Mijiti Salamaitiguli , Xie Yinyin , Lin Jingqi , Zhu Lixia , Meng Hongmei
Published: May 2024

Objective

The goal of epilepsy treatment is not only to control convulsive seizures but also to improve the quality of life of patients. This study aimed to investigate personality changes and the risk factors for their development in adult epilepsy patients.

Methods

A case-control study in a Class III, Class A hospital. The study comprised 206 adult epilepsy patients admitted to the Neurology Department at the First Hospital of Jilin University between October 2019 and December 2021, while the control group consisted of 154 community volunteers matched with the epilepsy group based on age, sex, and education. No additional treatment interventions were determined to be relevant in the context of this study.

Results

There is a significantly higher incidence of personality changes in epilepsy than in the general population, and patients with epilepsy were more likely to become psychoticism, neuroticism, and lie. Epilepsy patient’s employment rate and average quality of life score were significantly lower than that of the general population and had strong family intimacy but poor adaptability in this study. There are many factors affecting personality change: sleep disorders, economic status, quality of life, use of anti-seizure drugs, family cohesion and adaptability. The independent risk factors were quality of life and family cohesion.
Exercise, grit, and life satisfaction among Korean adolescents: a latent growth modeling analysis
Authors: Bae Myeong-Hun , Zhang Xiaoyu , Lee Je-Seong
Published: May 2024

Background

Life satisfaction among Korean students is declining substantially, and multifaceted improvement efforts are required.

Methods

We analyzed longitudinal change trajectories for exercise, grit, and life satisfaction levels among Korean adolescents using latent growth modeling with longitudinal data from the Korean Children and Youth Panel Surveys of 2,142 students (male: 1,070, female: 1,072) from sixth grade (2020) through eighth grade (2022).

Results

The model, which tracked linear changes in the students’ exercise, grit, and life satisfaction, showed consistent declines over three school years for all variables. We also identified a longitudinal causal relationship among exercise, grit, and life satisfaction. A higher grit intercept was associated with higher intercept for—and a partial mediating effect between—exercise and life satisfaction. The grit slope was positively related to the life satisfaction slope, and both the intercept and exercise slope had positive effects on life satisfaction. Moreover, grit had a longitudinal mediating effect between exercise and life satisfaction.

Conclusions

We discuss the longitudinal change trajectories of exercise, grit, and life satisfaction, the causal and mediating effects among them, and the implications of the findings. These findings bolster our understanding of Korean adolescents’ life satisfaction and have practical significance for designing programs to improve their quality of life.
Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial
Authors: Zhou Yongfang , Cheng Jiangli , Zhu Shuo , Dong Meiling , Lv Yinxia , Jing Xiaorong , Kang Yan
Published: May 2024

Background

Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS.

Methods

The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation.

The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated.

Trial ethics and dissemination

The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Trial registration

The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.
Association between the dietary inflammatory index and all-cause mortality in osteoarthritis
Authors: Song Genglu , Lu Yaoyu
Published: May 2024

Background

To investigate the association between the Dietary Inflammatory Index (DII) and all-cause mortality in patients with osteoarthritis (OA).

Methods

In this retrospective cohort study, data on OA patients were obtained from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. OA diagnosis was self-reported. The study population was divided into low and high DII groups based on the DII’s median. All-cause mortality was the outcome, which was determined via linkage to the National Death Index (NDI) until 31 December 2019. Multivariable Cox regression analyses were employed to investigate the association between the DII and all-cause mortality. The survival of the low and high DII groups was exhibited by Kaplan–Meier curves. Furthermore, subgroup analyses were carried out in terms of age and comorbidity.

Results

A total of 3804 patients with OA were included, with 1902 (50%) in the low DII group and 1902 (50%) in the high DII group. Patients with a high DII had a significantly greater risk of all-cause mortality than those with a low DII (HR = 1.21, 95%CI: 1.02–1.44, P = 0.025). A high DII was associated with a significantly increased risk of all-cause mortality compared with a low DII in patients aged ≥ 65 years [hazard ratio (HR) = 1.28, 95% confidence level (CI): 1.07–1.53, P = 0.006). Hypertensive patients with a high DII had a significantly greater risk of all-cause mortality than those with a low DII (HR = 1.25, 95%CI: 1.03–1.52, P = 0.025). For patients with cardiovascular disease (CVD), a high DII was associated with a significantly higher risk of all-cause mortality than a low DII (HR = 1.43, 95%CI: 1.17–1.75, P < 0.001). A high DII was associated with a significantly greater risk of all-cause mortality, as compared with a low DII in patients with chronic kidney disease (CKD) (HR = 1.22, 95%CI: 1.02–1.45, P = 0.026).

Conclusion

The DII was positively associated with the risk of all-cause mortality in patients with OA. This association differed by age, hypertension, CVD, and CKD. Adherence to diet with a low DII may be beneficial in prognosis improvement.
A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2
Authors: Wilkinson Piers , Jackson Brian , Fermor Hazel , Davies Robert
Published: May 2024

Background

Signal peptide (SP) engineering has proven able to improve production of many proteins yet is a laborious process that still relies on trial and error. mRNA structure around the translational start site is important in translation initiation and has rarely been considered in this context, with recent improvements in in silico mRNA structure potentially rendering it a useful predictive tool for SP selection. Here we attempt to create a method to systematically screen candidate signal peptide sequences in silico based on both their nucleotide and amino acid sequences. Several recently released computational tools were used to predict signal peptide activity (SignalP), localization target (DeepLoc) and predicted mRNA structure (MXFold2). The method was tested with Bone Morphogenetic Protein 2 (BMP2), an osteogenic growth factor used clinically for bone regeneration. It was hoped more effective BMP2 SPs could improve BMP2-based gene therapies and reduce the cost of recombinant BMP2 production.

Results

Amino acid sequence analysis indicated 2,611 SPs from the TGF-β superfamily were predicted to function when attached to BMP2. mRNA structure prediction indicated structures at the translational start site were likely highly variable. The five sequences with the most accessible translational start sites, a codon optimized BMP2 SP variant and the well-established hIL2 SP sequence were taken forward to in vitro testing. The top five candidates showed non-significant improvements in BMP2 secretion in HEK293T cells. All showed reductions in secretion versus the native sequence in C2C12 cells, with several showing large and significant decreases. None of the tested sequences were able to increase alkaline phosphatase activity above background in C2C12s. The codon optimized control sequence and hIL2 SP showed reasonable activity in HEK293T but very poor activity in C2C12.

Conclusions

These results support the use of peptide sequence based in silico tools for basic predictions around signal peptide activity in a synthetic biology context. However, mRNA structure prediction requires improvement before it can produce reliable predictions for this application. The poor activity of the codon optimized BMP2 SP variant in C2C12 emphasizes the importance of codon choice, mRNA structure, and cellular context for SP activity.
Pain assessment, cognitive and cortical changes with full mouth rehabilitation in a group of children
Authors: Metwally Nancy Mohamed , Ragab Osama Abd Allah , Kandil Mostafa Shaaban Husseiny , Elghareb Lamis Ahmed
Published: May 2024

Background

A change in professionals’ perspectives on the value of general anesthesia (GA) for pediatric patients, including those with disabilities, medical conditions, severe oral issues, and challenging behaviors. Full-mouth rehabilitation under GA allows for the comprehensive treatment of all oral health problems in a single visit, without requiring the child’s active participation. Extensive dental problems are often associated with severe dental pain, which can impact cognitive function, including perception, attention, memory, reasoning, language, communication, and executive functions. Individuals experiencing pain tend to perform less optimally cognitively.

Aim

This study aimed to investigate changes in cognition, brain function, and cortical alterations in children who underwent extensive dental rehabilitation under GA.

Patients andMethods

Thirty uncooperative, healthy children aged 6–12 with extensive dental issues were enrolled. Pain levels were assessed using the FLACC and WBFPS scales before treatment, one week after, and three months later. Cognitive assessments, including the WCST, processing speed, digit span, and Trail Making Test, as well as EEG measurements, were also performed.

Results

The results showed a significant improvement in pain levels reported by the children or their caregivers after the dental procedures, both at one week and three months. All cognitive measures, such as digit span, processing speed, and WCST performance, demonstrated substantial improvements after the treatment. The Trail Making Test also exhibited statistically significant variations before and after the dental procedures. Additionally, the MOCA test revealed a notable improvement in cognitive skills following the treatment. Furthermore, the EEG power ratio, an indicator of changes in the power balance within each frequency band, showed a statistically significant difference after the dental procedures.

Conclusion

the findings of this study suggest that full-mouth rehabilitation under GA can lead to improved pain management, as well as enhanced cognitive and brain functions in children.

Future perspectives

More clinical studies with a longer follow-up period and a different age range of children are required to investigate the connection between brain function and oral rehabilitation involving restorations or occlusion issues.
Mullerian adenosarcoma of the uterus with MASO: a case report of cervical adenosarcoma in a young female that never had sexual behavior
Authors: Chen Jia-Wei , Huang Ya-Jie , Wang Ling-Lu , Liu Jun-Jiang , Shi Ming-Mei , Li Na
Published: May 2024

Background

Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences.

Case presentation

A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed.

Conclusion

A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.
Barriers and future improvements of workplace-based learning in Korean medicine clinical clerkship: perspectives of graduates
Authors: Cho Eunbyul , Lee Do-Eun , Lee Dongha , Jung Hyun-Jong
Published: May 2024

Background

Workplace-based learning (WPBL) has emerged as an essential practice in healthcare education. However, WPBL is rarely implemented in Korean medicine (KM) due to the passive attitude of teachers and possible violation of medical laws that limit the participation of trainees in medical treatment. In this study, we implemented WPBL in the clinical clerkship of Acupuncture and Moxibustion Medicine at a single College of KM and explored the barriers and future improvements of WPBL.

Methods

The WPBL was implemented from January to July 2019. During the clerkship, each senior student was assigned an inpatient at the university hospital. WPBL was conducted as follows: patient presentation by the supervisor, interaction with the patient at the bedside, preparation of medical records, oral case presentation, and discussion with feedback. The student performed a physical examination and review of systems as a clinical task. In addition, six doctors of KM who are currently practicing after three years of WPBL were interviewed in September 2022 to investigate the real-world effects and unmet needs of WPBL in their workplaces.

Results

Two major themes identified from the interview were: “the experience of novice doctors of KM with KM practice” and “Current state of KM clinical education.” The five subcategories were: “Clinical competency priorities vary according to the KM workplace,” “Difficulties faced by doctors of KM immediately after graduation,” “WPBL experience of the interviewees,” “Necessary but difficult to implement real patient learning,” and “Unmet needs for clinical clerkship in KM.”

Conclusion

It is essential to consider the unique characteristics of KM practice and the duties required in various workplaces for successful WPBL. We anticipate our study to be a starting point for improving the WPBL and addressing the unmet needs in KM clinical education.
Identifying potential drug targets for idiopathic pulmonary fibrosis: a mendelian randomization study based on the druggable genes
Authors: Liu Zetao , Peng Zhiyu , Lin Huahang , Zhou Ke , Liang Linchuan , Cao Jie , Huang Zhaokang , Mei Jiandong
Published: May 2024

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF.

Methods

We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings.

Results

The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47–0.97).

Conclusion

IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.
Delineating three-dimensional behavior of uveal melanoma cells under anchorage independent or dependent conditions
Authors: Goyeneche Alicia A. , Lasiste Jade M. E. , Abdouh Mohamed , Bustamante Prisca , Burnier Julia V. , Burnier Miguel N.
Published: May 2024

Background

Although rare, uveal melanoma (UM) is a life-threatening malignancy. Understanding its biology is necessary to improve disease outcome. Three-dimensional (3D) in vitro culture methods have emerged as tools that incorporate physical and spatial cues that better mimic tumor biology and in turn deliver more predictive preclinical data. Herein, we comprehensively characterize UM cells under different 3D culture settings as a suitable model to study tumor cell behavior and therapeutic intervention.

Methods

Six UM cell lines were tested in two-dimensional (2D) and 3D-culture conditions. For 3D cultures, we used anchorage-dependent (AD) methods where cells were embedded or seeded on top of basement membrane extracts and anchorage-free (AF) methods where cells were seeded on agarose pre-coated plates, ultra-low attachment plates, and on hanging drops, with or without methylcellulose. Cultures were analyzed for multicellular tumor structures (MCTs) development by phase contrast and confocal imaging, and cell wellbeing was assessed based on viability, membrane integrity, vitality, apoptotic features, and DNA synthesis. Vascular endothelial growth factor (VEGF) production was evaluated under hypoxic conditions for cell function analysis.

Results

UM cells cultured following anchorage-free methods developed MCTs shaped as spheres. Regardless of their sizes and degree of compaction, these spheres displayed an outer ring of viable and proliferating cells, and a core with less proliferating and apoptotic cells. In contrast, UM cells maintained under anchorage-dependent conditions established several morphological adaptations. Some remained isolated and rounded, formed multi-size irregular aggregates, or adopted a 2D-like flat appearance. These cells invariably conserved their metabolic activity and conserved melanocytic markers (i.e., expression of Melan A/Mart-1 and HMB45). Notably, under hypoxia, cells maintained under 3D conditions secrete more VEGF compared to cells cultured under 2D conditions.

Conclusions

Under an anchorage-free environment, UM cells form sphere-like MCTs that acquire attributes reminiscent of abnormal vascularized solid tumors. UM cells behavior in anchorage-dependent manner exposed diverse cells populations in response to cues from an enriched extracellular matrix proteins (ECM) environment, highlighting the plasticity of UM cells. This study provides a 3D cell culture platform that is more predictive of the biology of UM. The integration of such platforms to explore mechanisms of ECM-mediated tumor resistance, metastatic abilities, and to test novel therapeutics (i.e., anti-angiogenics and immunomodulators) would benefit UM care.
Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin
Authors: Ventocilla Julio A. , Tapia L. Lorena , Ponce Reynaldo , Franco Adriano , Leelawong Mindy , Aguiar Joao C. , Baldeviano G. Christian , Wilder Brandon K.
Published: May 2024

Background

Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity.

Methods

Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used.

Results

In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58–99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9–35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses.

Conclusions

These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.
Rabies death in an adolescent tribal girl diagnosed postmortem, in Kerala - the precious life, preventable loss and equity concerns
Authors: Nujum Zinia T. , Indu Pillaveetil Sathyadas , Ramesh Jeena , Philip Rekha Rachel , S. Smitha , A. R. Seena. , N. Laila Raji , Balaram N. A.
Published: May 2024

Background

Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises.

Methods

The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations.

Results

The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world.

Conclusions

To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health.
Phenotypic and genotypic analysis of antimicrobial resistance and population structure of gastroenteritis-related Aeromonas isolates
Authors: Sagas Dana , Hershko Yizhak , Levitskyi Katia , Strauss Merav , Slutzkin Matan , Chazan Bibiana , Adler Amos
Published: May 2024

Background

The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them.

Methods

This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results.

Results

The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1–2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the blaOXA genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other β-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission.

Conclusions

A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.
Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening
Authors: Zhong Yiye , Le Huangying , Zhang Xue , Dai Yao , Guo Fang , Ran Xiaojuan , Hu Guohong , Xie Qi , Wang Dawei , Cai Yujia
Published: May 2024

Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening. In models of glioblastoma (GBM) and triple-negative breast cancer (TNBC), we showed that the combination of OV and a PARP inhibitor (PARPi) exhibited superior efficacy compared to either monotherapy. Additionally, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy sensitized TNBC to immune checkpoint blockade, and the incorporation of an immune checkpoint inhibitor (ICI) further increased the survival rate of tumor-bearing mice. The combination of PARPi and ICI synergistically enhanced the ability of OV to establish durable tumor-specific immune responses. Our study effectively overcomes the inherent limitations of OV therapy, providing valuable insights for the clinical treatment of TNBC, GBM, and other malignancies.
Enough with simplifying: “eat less and move more”: at what point are we with the treatment of excess weight in paediatrics?
Authors: Tanas Rita , Corsello Giovanni , Lera Riccardo , Marsella Maria , Bernasconi Sergio
Published: May 2024

Background

For years politics and healthcare, faced with the progressive increase in the prevalence of overweight and obesity in childhood, have wondered how to stem it and reduce its consequences on health without finding a valid, effective and applicable solution. Many studies have been written initially on what to prescribe, then on why not to prescribe and how to approach people in a new and more effective way to improve their behaviors, considered the main cause of excess weight. Over the last twenty years it has been highlighted that no diet or physical exercise is truly effective and not even global changes in lifestyle guarantee the large weight reductions traditionally expected, despite offering significant health advantages. A new approach is necessary and we must begin by working on ourselves.

Main body

We examined literature on weight stigma and considered expert opinions, as well as feedback from parents/caregivers and patients. Literature on stigma has grown enormously in recent years, and finally considers the opinion of parents and patients. By interviewing patients with obesity, it was discovered that very often healthcare workers do not communicate the diagnosis and, if they do, they have a blaming attitude, holding patients responsible for their weight. Furthermore, when these people become aware of their obesity and seek treatment, they do not find adequate professionals and centers. Failure was mostly due to the enormous burden of obesity stigma and discrimination which, especially in children and young people, encourages internalization of the problem and takes away their self-efficacy, desire and ability to take care of themselves.

Conclusions

New actions are needed to change all this. We propose “Training, Networking and Contrasting Weight Stigma”. Now that we’ve figured out where to start, we should get going. And yet, nothing is changing!
Comparison of atherogenic indices for predicting the risk of metabolic syndrome in Southwest Iran: results from the Hoveyzeh Cohort Study (HCS)
Authors: Babaahmadi‐Rezaei Hossein , Raeisizadeh Maedeh , Zarezade Vahid , Noemani Kourosh , Mashkournia Ahmad , Ghaderi-Zefrehi Hossein
Published: May 2024

Background

Metabolic syndrome (MetS) is a cluster of risk factors related to diabetes and cardiovascular disease (CVD). Given that early identification of MetS might decrease CVD risk, it is imperative to establish a simple and cost-effective method to identify individuals at risk of MetS. The purpose of this study was to explore the relationships between several atherogenic indices (including AIP, TyG index, non-HDL-C, LDL-c/HDL-c, and TC/HDL-c) and MetS, and to assess the ability of these indices to predict MetS.

Methods

The present cross-sectional study was conducted using baseline data from 9809 participants of the Hoveyzeh Cohort Study (HCS). MetS was defined based on the International Diabetes Federation (IDF). To examine the discriminatory abilities of each atherogenic indices in the identification of MetS, a receiver-operating characteristic curve was conducted. Logistic regression analysis was also performed to evaluate the relationship between atherogenic indices and MetS.

Results

All of the atherogenic indices including the TyG index, AIP, non-HDL-C, TC/HDL-c, and LDL-c/HDL-c were significantly higher in participants with MetS than in those without MetS. According to the ROC curve analysis, the TyG index revealed the highest area under the curve (0.79 and 0.85 in men and women, respectively), followed by the AIP (0.76 and 0.83 in men and women, respectively). The best cutoff values for the TyG index and AIP were 8.96 and 0.16 for men and 8.84 and 0.05 for women, respectively. The TyG index and AIP were also strongly associated with MetS.

Conclusion

Among the 5 atherogenic indices evaluated, the TyG index and AIP were strongly related to MetS. The TyG index also demonstrated superior discriminative ability compared to other atherogenic indices in predicting MetS.
Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly
Authors: Niimi Yoshiki , Janelidze Shorena , Sato Kenichiro , Tomita Naoki , Tsukamoto Tadashi , Kato Takashi , Yoshiyama Kenji , Kowa Hisatomo , Iwata Atsushi , Ihara Ryoko , Suzuki Kazushi , Kasuga Kensaku , Ikeuchi Takeshi , Ishii Kenji , Ito Kengo , Nakamura Akinori , Senda Michio , Day Theresa A. , Burnham Samantha C. , Iaccarino Leonardo , Pontecorvo Michael J. , Hansson Oskar , Iwatsubo Takeshi
Published: May 2024

Background

Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer’s disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.

Methods

We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma Aβ and p-tau217 assessments, and Aβ-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma Aβ(1-42) (Aβ42) and Aβ(1-40) (Aβ40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly).

Results

Aβ-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aβ42/Aβ40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aβ-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/Aβ42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aβ42/Aβ40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aβ42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, Aβ42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aβ42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914).

Conclusions

Combination of plasma Aβ-related biomarkers and p-tau217 exhibits high performance when predicting Aβ-PET positivity. Adding basic clinical information (i.e., age, sex, APOE ε genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aβ-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD.
Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis
Authors: Duan Yanan , Chen Xiteng , Shao Hui , Li Yongtao , Zhang Zhihui , Li Huan , Zhao Chuan , Xiao Hong , Wang Jiawei , Zhang Xiaomin
Published: May 2024

Background

Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73.

Methods

To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73.

Results

Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion.

Conclusion

Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.
CineMol: a programmatically accessible direct-to-SVG 3D small molecule drawer
Authors: Meijer David , Medema Marnix H. , van der Hooft Justin J. J.
Published: May 2024

Effective visualization of small molecules is paramount in conveying concepts and results in cheminformatics. Scalable vector graphics (SVG) are preferred for creating such visualizations, as SVGs can be easily altered in post-production and exported to other formats. A wide spectrum of software applications already exist that can visualize molecules, and customize these visualizations, in many ways. However, software packages that can output projected 3D models onto a 2D canvas directly as SVG, while being programmatically accessible from Python, are lacking. Here, we introduce CineMol, which can draw vectorized approximations of three-dimensional small molecule models in seconds, without triangulation or ray tracing, resulting in files of around 50–300 kilobytes per molecule model for compounds with up to 45 heavy atoms. The SVGs outputted by CineMol can be readily modified in popular vector graphics editing software applications. CineMol is written in Python and can be incorporated into any existing Python cheminformatics workflow, as it only depends on native Python libraries. CineMol also provides programmatic access to all its internal states, allowing for per-atom and per-bond-based customization. CineMol’s capacity to programmatically create molecular visualizations suitable for post-production offers researchers and scientists a powerful tool for enhancing the clarity and visual impact of their scientific presentations and publications in cheminformatics, metabolomics, and related scientific disciplines.

Scientific contribution

We introduce CineMol, a Python-based tool that provides a valuable solution for cheminformatics researchers by enabling the direct generation of high-quality approximations of two-dimensional SVG visualizations from three-dimensional small molecule models, all within a programmable Python framework. CineMol offers a unique combination of speed, efficiency, and accessibility, making it an indispensable tool for researchers in cheminformatics, especially when working with SVG visualizations.