bluuebunny/crossref_metadata_2025 huggingface dataset:
Research status and challenges of Mycoplasma pneumoniae pneumonia in children: A bibliometric and visualization analysis from 2011 to 2023
Authors: Liu Congcong , Wang Rui , Ge Shuyi , Wang Binding , Li Siman , Yan Bohua
Published: March 2024

Background:

Mycoplasma pneumoniae (MP) infections occur in regional outbreaks every 3 to 7 years, lasting up to 2 years. Since this fall, there has been a significant rise in MP infections among children in China, indicating a regional epidemiological trend that imposes an increased national public health burden. To date, bibliometric methods have not been applied to studies on MP infection in children.

Methods:

We searched for all relevant English publications on MP pneumonia in children published from 2011 to 2023 using Web of Science. Analytical software tools such as Citespace and VOSviewer were employed to analyze the collected literature.

Results:

993 articles on MP pneumonia in children were published in 338 academic journals by 5062 authors affiliated with 1381 institutions across 75 countries/regions. China led in global productivity with 56.19%. Among the top 10 prolific organizations, 8 were Chinese institutions, with Soochow University being the most active, followed by Capital Medical University and Zhejiang University. Zhimin Chen from Zhejiang University School of Medicine exhibited the highest H-index of 32. Keyword co-occurrence network analysis revealed 7 highly relevant clusters.

Conclusion:

The current research hotspots and frontiers in this field are primarily MP pneumonia, refractory MP pneumonia, lactate dehydrogenase, asthma, and biomarker. We anticipate that this work will provide novel insights for advancing scientific exploration and the clinical application of MP pneumonia in children.
Intensity of statin therapy and primary prevention of cardiovascular in Korean patients with dyslipidemia
Authors: Song Sun Ok , Kang Min Jin , Suh Sunghwan
Published: March 2024

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ± 6.6 months. The mean age of all participants at baseline was 59.2 ± 8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ± mg/dL, the mean duration of taking statins was 337.4 ± 52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.
The outcome of early screening and treatment of developmental dysplasia of the hip in infants and toddlers in the Northern Guizhou region
Authors: Lv Xin , Yu Song , Zhang Tianjiu , Yang Xiaohong , Xu Yanpeng , Li Tangjiang
Published: March 2024

This study is an observation of the early screening and treatment effect of infant developmental dysplasia of the hip (DDH) in an area in China. From January 2016 to December 2017, we selected infants and toddlers with high-risk factors for DDH, such as asymmetric gluteal folds, unequal length of lower limbs, and limited hip joint abduction, who visited the Department of Child Health Care and the Outpatient Clinic of Pediatric Orthopedics at the Affiliated Hospital of Zunyi Medical University. In total, 1485 cases were divided into age groups, examined using Graf ultrasound and X-ray, and the results were analyzed. Meanwhile, early interventions were actively adopted for cases with abnormalities during the screening. The detection rates of DDH were 24.0%, 2.8%, 9.3%, and 12.2% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. Early and individualized corrective conservative treatment was considered for children with abnormalities, and the cure rates were 87.0%, 65.7%, 41.0%, and 16.7% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. There was a statistically significant difference in the detection and cure rates of DDH in infants and toddlers of different ages (P < .01).
The incidence and risk factors of secondary epilepsy after viral encephalitis in children: A 10-year single-center retrospective analysis
Authors: Hu Yang , Huang Bo , Zhu Mengsha , Sun Suzhen , Zhang Guiying
Published: March 2024

Secondary epilepsy is a common concomitant disease of viral encephalitis (VE) in children. However, the risk factors for secondary epilepsy after VE remain debated. The aim of this study was to perform a 10-year single-center retrospective analysis to investigate the incidence and risk factors of secondary epilepsy after VE in children. A total of 8691 patients suffered from VE in our hospital between December 2011 and February 2022 were included. The patients were divided into control group (Group C) and epilepsy group (Group E) according to whether they followed secondary epilepsy. Information about treatment process was collected from medical records to determine the incidence. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors. In the current study, the occurrence of secondary epilepsy after VE in pediatric patients was 10.99% (385 of 3503). The results of univariate and multivariate analysis showed that unconsciousness, convulsions, times of epilepsy >2, epileptiform discharge of Electroencephalogram (EEG), and cortical and subcortical damage of magnetic resonance imaging/computer tomography were the significant risk factors for secondary epilepsy after VE. Nearly one tenth of pediatric patients suffered from secondary epilepsy after VE. Interventions for identified risk factors should be used to prevent the occurrence of secondary epilepsy.
Visualization analysis of mitochondrial dynamics in heart failure based on bibliometrics: Trends, hotspots, and topics
Authors: Jia Sihan , Lian Yanjie , Li Sinai , Liu Hongxu , Shang Juju
Published: March 2024

This study aimed to conduct a visual analysis of the relevant literature on mitochondrial dynamics in heart failure, explore the research progress, frontier topics, and development trends in this field, and provide references for the study concerning mitochondrial dynamics in the prevention and treatment of heart failure. The Web of Science was searched from inception to October 1, 2023 to identify relevant English literature on mitochondrial dynamics in heart failure. Bibliometric methods were utilized to statistically analyze the eligible literature, and CiteSpace 6.2.R5 software was employed to visualize data such as countries of publication, institutions, authors, and keywords. A total of 1755 Science Citation Index articles were included. The global publication volume showed an increasing trend year by year, with China and the United States having the most publications, and the United States displaying the highest centrality in publications. As revealed by keyword and citation analyses, the research hotspots and frontiers in this field mainly included the pathogenesis of heart failure, mitochondrial dynamics markers, mitochondrial quality control, and potential therapeutic targets for heart failure. Research on mitochondrial dynamics in heart failure is under vigorous development. It is a development trend in this research field to explore the differential gene expression and molecular mechanisms of targeted treatment in the mitochondrial dynamics in heart failure, which will contribute to the formulation of new strategies for the prevention and treatment of heart failure.
Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre
Authors: Stephens Ian J.B. , Murphy Brenda , Burns Lucy , McCawley Niamh , McNamara Deborah A. , Burke John P.
Published: March 2024

Objective

Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC.

Methods

Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS).

Results

A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6–12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy (P = 0.85) or biologic use (P = 0.24) and morbidity. Increasing age was associated with prolonged LOS (P = 0.01). Laparoscopic approach (7 vs. 12 days P =0.01, 36.8% vs. 45% P = 0.66) was associated with reduced LOS and morbidity.

Conclusion

This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.
Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-neutrophil (PN) index in locally advanced rectal cancer patients: a retrospective cohort study
Authors: Morais Marina , Fonseca Telma , Machado-Neves Raquel , Honavar Mrinalini , Coelho Ana Rita , Lopes Joanne , Guerreiro Emanuel , Carneiro Silvestre
Published: March 2024

Introduction:

In locally advanced rectal cancers (LARC), tumour node metastasis (TNM) staging is far from optimal. The authors aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis.

Methods:

Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centres. A Cox regression and Kaplan–Meier analysis were performed.

Results:

Post-treatment platelet-to-lymphocyte ratio (PLR) predicted pathological complete response. The neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas the platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, the PN index predicted patients with a higher risk of disease-free survival.

Conclusion:

Blood parameters might allow the definition of subgroups of risk beyond TNM for the application of different therapeutic strategies.
The level of medical students’ knowledge regarding the prevention of cervical cancer
Authors: Shrateh Oadi N. , Habib Ashna , Jalamneh Basil , Omar Belal M.M. , Naasan Mashhour
Published: March 2024

Background:

In Palestine, cervical cancer is the third most common gynaecological cancer, exhibiting higher mortality rates compared to regional counterparts. Late-stage diagnosis and limited awareness contribute to this disparity. This study aims to assess the awareness of Palestinian medical students regarding cervical cancer prevention.

Methods:

A questionnaire-based survey involving 532 medical students from various Palestinian universities was conducted between October 2023 and December 2023. The survey encompassed closed-ended quantitative and demographic questions distributed through social media.

Results:

The study was carried out on a group of 532 medical students (66.3% women and 33.6% men), (average age 21.7 years). Most students (77.7%) knew that the main risk factor for cervical cancer was human papillomavirus (HPV) infection. Participants doing the internship had the greatest knowledge, whereas students from the first year had the poorest knowledge about the main risk factors for cancer of the cervix. Only about half, 50.2% of all students, knew that in Palestine, there is no screening program. 84.4% of students correctly indicated that the cervical cancer screening test is a pap smear test. 41.4% of respondents knew that microscopic evaluation of the exfoliated cells from the vaginal part of the cervix is the screening test for cervical cancer which is used. Only about half of the students (45.1%) knew that there were no specific early symptoms of cervical cancer.

Conclusions:

This study highlights the need for enhanced education, particularly regarding screening program awareness, among Palestinian medical students. Addressing these knowledge gaps is crucial for effective preventive strategies.
Efficacy of bone ring grafts for the reconstruction of alveolar ridge deficiencies: a systematic review. Part II: animal trials
Authors: Zhao Ruimin , Zhang Zhelun , Yang Peixuan , Xu Xu , Yuan Zhenfei , Gong Jiaming
Published: March 2024

Background:

Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols.

Methods:

Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949).

Results:

Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap.

Conclusions:

Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.
An abrupt fatal hemothorax in a stable COVID-19 patient: a case report with literature review
Authors: Ghabally Mike , Shebli Baraa , Yahaya Hassan , Al Ali Yasin , Alhames Samer
Published: March 2024

Introduction and importance:

COVID-19 has been widely spread in the last 2 years. Hemothorax is considered one of the rarest complications of COVID-19.

Case presentation:

The authors herein report a case of a 52-year-old patient of COVID-19 that was complicated with abrupt massive hemothorax with hemodynamic instability. Emergent thoracostomy drained almost 4500 ml of blood within 48 h. Thoracoscopy was also performed draining an additional 2000 ml of blood and clots. No further bleeding occurred. Unfortunately, the patient died of septic shock and multiorgan dysfunction.

Clinical discussion:

Hemothorax has been reported in seven patients with COVID-19 in the medical literature. Six patients had severe infection with veno-venous extra-corporeal membranous oxygenation (VV-ECMO), and the seventh patient had necrotizing pneumonia. To our knowledge, this represents the first patient of an abrupt massive hemothorax in a COVID-19 patient just before recovery.

Conclusion:

Post-COVID-19 hemothorax should be suspected in severe cases with sudden clinical deterioration and evidence of pleural effusion.
Diagnosing adjustment disorder in patients with cancer: evaluation of the adherence, interrater agreement, and content of a guideline-based interview
Authors: Wijnhoven Lonneke M.A. , van Zutphen Linda , Custers José A.E. , van Beek Florie E. , Holtmaat Karen , Jansen Femke , Verdonck-de Leeuw Irma M. , Kwakkenbos Linda , Prins Judith B.
Published: March 2024

Background:

The aim of this study was to evaluate the adherence, interrater agreement, and content of a guideline-based semistructured interview for adjustment disorder (AD) in patients with cancer.

Methods:

In total, 120 AD interviews with patients with cancer were performed by 9 trained psychologists. The interview contained topics related to stressors, resilience, and symptoms and complaints. Audiotaped interviews of 72 patients were available. Adherence to the interview manual was scored by two researchers independently, and the average adherence was calculated per topic. Interrater agreement was calculated using Cohen's Kappa. The content of the interviews was evaluated using thematic analysis of the transcribed interviews of patients with an AD diagnosis.

Results:

In the interviews, 97% of the topics were covered at least briefly and 78% of all topics were addressed at least adequately. Interviewers asked questions regarding stressors and symptoms and complaints more thoroughly compared with resilience. The interrater agreement regarding the AD diagnosis was moderate (Kappa 0.55). The content analysis showed that stressors and resilience can be additionally specified into physical, psychological, spiritual, and social themes, which are relevant to explore in the context of an AD diagnosis after cancer.

Conclusion:

The guideline-based interview for AD identifies problems and protective factors with adequate adherence and moderate agreement. A balanced investigation of stressors, resilience, and symptoms is important for optimal clinical decision-making regarding AD in the context of cancer.
Para Powerlifting Performance
Authors: Lopes-Silva João Paulo , Franchini Emerson , Kons Rafael
Published: March 2024

Objective

We analyzed the retrospective performance of para powerlifters over 8 yrs considering sex, the origin of impairment, and sport classification of para powerlifting.

Design

This retrospective study analyzed data from 6791 (4613 and 2178 for male and female, respectively) individual results from 1634 athletes’ performances. We collected absolute load (in kilograms), relative load (in kilogram/body mass), chronological age and origin of impairment (acquired or congenital), and sport classification (leg length difference, limb deficiency, range of movement, impaired muscle power, hypertonia, ataxia, athetosis, and short stature of para powerlifters.

Results

Males were stronger than females thorough the years with acquired impairment being stronger than congenital impairment. Para powerlifters with acquired impairment were older compared with congenital impairment over the years. Acquired impairment males won 60% more medals than the congenital group. There was a significant association between competition achievement and sports class classification, with a higher number of medals for limb deficiency than other sports classes.

Conclusions

These results demonstrate that the sex, origin of impairment, and sports classification influence performance of athletes in para powerlifting. Thus, this information can help athletes, coaches, sport managers, and sport institutions involved in the sport of para powerlifting.
Risk of Stroke Among HIV Patients: A Systematic Review and Meta-analysis of Global Studies and Associated Comorbidities
Authors: Moawad Mostafa Hossam El Din , Mohamed Shalaby Mahmoud Mohamed , Hamouda Esraa , Mahfouz Amany , Mouffokes Adel , Hamouda Heba , Abbas Abdallah , Abdelgawad Hussien Ahmed H.
Published: March 2024

Background:

Despite advancements in the management of HIV infection, the factors contributing to stroke development among HIV-positive individuals remain unclear. This systematic review and meta-analysis aim to identify and evaluate the relative risk factors associated with stroke susceptibility in the HIV population.

Methods:

A comprehensive search was conducted in PubMed, Scopus, and Web of Science databases to identify studies investigating the risk of stroke development in HIV patients and assessing the role of different risk factors, including hypertension, diabetes, dyslipidemia, smoking, sex, and race. The quality assessment of case–control studies was conducted using the Newcastle–Ottawa Scale, whereas cohort studies were assessed using the National Institute of Health tool. Meta-analyses were performed using a random-effects model to determine pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs).

Results:

A total of 18 observational studies involving 116,184 HIV-positive and 3,184,245 HIV-negative patients were included. HIV-positive patients exhibited a significantly higher risk of stroke compared with HIV-negative patients [OR (95% CI): 1.31 (1.20 to 1.44)]. Subgroup analyses revealed increased risks for both ischemic stroke [OR (95% CI): 1.32 (1.19 to 1.46)] and hemorrhagic stroke [OR (95% CI): 1.31 (1.09 to 1.56)]. Pooled adjusted HRs showed a significant association between stroke and HIV positivity (HR: 1.37, 95% CI: 1.22 to 1.54). Among HIV-positive patients with stroke, hypertension [OR (95% CI): 3.5 (1.42 to 8.65)], diabetes [OR (95% CI): 5 (2.12 to 11.95)], hyperlipidemia, smoking, male gender, and black race were associated with an increased risk.

Discussion:

Our study revealed a significant increased risk of stroke development among people with HIV. A multitude of factors, encompassing sociodemographic characteristics, racial background, underlying health conditions, and personal behaviors, significantly elevate the risk of stroke in individuals living with HIV. The use of observational studies introduces inherent limitations, and further investigations are necessary to explore the underlying mechanisms of stroke in people with HIV for potential treatment strategies.

Conclusion:

HIV patients face a higher risk of stroke development, either ischemic and hemorrhagic strokes. Hypertension, diabetes, hyperlipidemia, smoking, male gender, and black race were identified as significant risk factors. Early identification and management of these risk factors are crucial in reducing stroke incidence among patients living with HIV.
Nasopharyngeal carriage rate, serotype distribution, and antimicrobial profiles of Streptococcus pneumoniae among patients with acute respiratory tract infection in Manado, North Sulawesi, Indonesia
Authors: Purwanto Diana Shintawati , Khoeri Miftahuddin Majid , Tafroji Wisnu , Margaretha Kaligis Stefana Helena , Wilar Rocky , Johnson Kepel Billy , Raranta Hessyani Patricia Theodora , Gaghiwu Lidia , Hammerschmidt Sven , Ervina Waode Fifin , Safari Dodi
Published: March 2024

We studied the carriage rate, distribution of serotype, and antimicrobial profile of Streptococcus pneumoniae (S. pneumoniae) among patients with acute respiratory tract infections (ARTI) in two primary health centres and a tertiary referral hospital from 2019 to 2020 in Manado, North Sulawesi, Indonesia before 13-valent pneumococcal conjugate vaccine (PCV13) introduction. A total of 106 nasopharyngeal swab samples were collected from children and adult patients. Serotyping of S. pneumoniae strain was performed by sequential multiplex PCR and Quellung reaction. Antimicrobial profile was performed by the disc diffusion method. We identified thirty-one patients carried S. pneumoniae strains (29 %). The S. pneumoniae carriage rate was found to be higher among children aged 2–5 years (13/32; 40.6 %) than in children under 1 year (8/27; 29.6 %), children and adolescents under 18 years of age (5/20; 25.0 %) and adult patients (5/27; 18.5 %). The distribution of serotypes varied, including 14, 18C, 19A, 23F, 19F and 35B (two strains each) and 1, 3, 6B, 6C, 31, 9V, 15C, 16F, 17F, 23A, 35F (one strain each) and non-typeable (9/31; 29 %). We found S. pneumoniae isolates were susceptible to vancomycin (30/31; 97 %), chloramphenicol (29/31; 94 %), clindamycin (29/31; 94 %), erythromycin (22/31; 71 %), azithromycin (22/31; 71 %), tetracycline (14/31; 45 %), penicillin (11/31; 35 %), and sulfamethoxazole/trimethoprim (10/31; 32 %). This study provides supporting baseline data on distribution of serotype and antimicrobial profile of S. pneumoniae among patients with ARTI before PCV13 introduction in Manado, North Sulawesi, Indonesia.
Oxidative stress governs mosquito innate immune signalling to reduce chikungunya virus infection in Aedes-derived cells
Authors: Mehta Divya , Chaudhary Sakshi , Sunil Sujatha
Published: March 2024

Arboviruses such as chikungunya, dengue and zika viruses cause debilitating diseases in humans. The principal vector species that transmits these viruses is the Aedes mosquito. Lack of substantial knowledge of the vector species hinders the advancement of strategies for controlling the spread of arboviruses. To supplement our information on mosquitoes’ responses to virus infection, we utilized Aedes aegypti-derived Aag2 cells to study changes at the transcriptional level during infection with chikungunya virus (CHIKV). We observed that genes belonging to the redox pathway were significantly differentially regulated. Upon quantifying reactive oxygen species (ROS) in the cells during viral infection, we further discovered that ROS levels are considerably higher during the early hours of infection; however, as the infection progresses, an increase in antioxidant gene expression suppresses the oxidative stress in cells. Our study also suggests that ROS is a critical regulator of viral replication in cells and inhibits intracellular and extracellular viral replication by promoting the Rel2-mediated Imd immune signalling pathway. In conclusion, our study provides evidence for a regulatory role of oxidative stress in infected Aedes-derived cells.
Microbial biofilms on macroalgae harbour diverse integron gene cassettes
Authors: Freddi Stefano , Rajabal Vaheesan , Tetu Sasha G. , Gillings Michael R. , Penesyan Anahit
Published: March 2024

Integrons are genetic platforms that capture, rearrange and express mobile modules called gene cassettes. The best characterized gene cassettes encode antibiotic resistance, but the function of most integron gene cassettes remains unknown. Functional predictions suggest that many gene cassettes could encode proteins that facilitate interactions with other cells and with the extracellular environment. Because cell interactions are essential for biofilm stability, we sequenced gene cassettes from biofilms growing on the surface of the marine macroalgae Ulva australis and Sargassum linearifolium. Algal samples were obtained from coastal rock platforms around Sydney, Australia, using seawater as a control. We demonstrated that integrons in microbial biofilms did not sample genes randomly from the surrounding seawater, but harboured specific functions that potentially provided an adaptive advantage to both the bacterial cells in biofilm communities and their macroalgal host. Further, integron gene cassettes had a well-defined spatial distribution, suggesting that each bacterial biofilm acquired these genetic elements via sampling from a large but localized pool of gene cassettes. These findings suggest two forms of filtering: a selective acquisition of different integron-containing bacterial species into the distinct biofilms on Ulva and Sargassum surfaces, and a selective retention of unique populations of gene cassettes at each sampling location.
Patient-reported outcomes relevant to post-discharge trauma patients in urban India
Authors: David Siddarth , Gerdin Wärnberg Martin ,   Trauma life support training Effectiveness Research Network (TERN) collaborators
Published: March 2024

Trauma is a major global health burden with long-term consequences to patients. Patient-reported outcomes (PROs) are increasingly being recognized and utilised to improve trauma care. It is imperative to identify the PROs that are most relevant, applicable, and suitable to a context. However, there is limited research on PROs in trauma care in low- and middle-income countries, like India, that bear a disproportionate burden of global trauma. This paper aims to examine PROs considered to be most relevant for trauma patients after discharge in the context of urban India.

We conducted semi-structured qualitative interviews of 11 adult post discharge trauma patients, across demographic and injury groups, and two persons working with trauma patients from five tertiary-care public hospitals in the Indian cities of Mumbai and Kolkata. We performed thematic analysis to identify themes within the participants responses on PROs important to them based on their experiences.

Four themes emerged in the analysis of the participant interviews. The need for full physical functioning, the need to address psychological consequences, the need to alleviate economic cost of trauma, and the need for social interactions. Outcomes related to these themes were most relevant to the participants.

The findings of this paper can help researchers and clinicians select appropriate PROs, based on the four themes, for trauma research and to improve trauma care in urban India. Future research should focus on PROs relevant to specific demographic and injury groups in India and other LMICs.
Cell-free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer
Authors: Werner Bonnita , Powell Elyse , Duggan Jennifer , Cortesi Marilisa , Lee Yeh Chen , Arora Vivek , Athavale Ramanand , Dean Michael , Warton Kristina , Ford Caroline E
Published: March 2024

Background The emergence of targeted therapies and predictive biomarkers is transforming the ovarian cancer treatment paradigm. However, the demand for high quality, tumour-enriched samples for biomarker profiling can be limited by access to adequate tissue samples. The use of cell-free DNA (cfDNA) in ascites presents a potential solution to this clinical challenge. Methods A unique set of sequential ascites-derived cfDNA samples (26 samples from 15 human participants) were collected from people with ovarian cancer (age range 36-82 years). cfDNA was sequenced using targeted next-generation sequencing, along with matched DNA from ascites-derived tumour cells (n=5) and archived FFPE-tissue from surgery (n=5). Results Similar tumour purity, variant detection and reference alignment were achieved with cfDNA when compared to FFPE and ascites derived tumour cell DNA, as well as improved coverage. No artefactual single-base mutation signatures were identified in cfDNA. Combined analysis of large-scale genomic alterations, loss of heterozygosity and tumour mutation burden identified 6 cases of high genomic instability (including 4 with pathogenic variants in BRCA1 and BRCA2). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case study where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Conclusions Ascites cfDNA successfully identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. These findings advocate for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy.
The WERA Cancer Center Matrix: Strategic Management of Patient Access to Precision Oncology in a Large and Mostly Rural Area of Germany
Authors: Krebs Markus , Haller Florian , Spörl Silvia , Gerhard-Hartmann Elena , Utpatel Kirsten , Maurus Katja , Kunzmann Volker , Chatterjee Manik , Venkataramani Vivek , Maatouk Imad , Bittrich Max , Einwag Tatjana , Meidenbauer Norbert , Tögel Lars , Hirsch Daniela , Dietmaier Wolfgang , Keil Felix , Scheiter Alexander , Immel Alexander , Heudobler Daniel , Einhell Sabine , Kaiser Ulrich , Sedlmeier Anja M. , Maurer Julia , Schenkirsch Gerhard , Jordan Frank , Schmutz Maximilian , Dintner Sebastian , Rosenwald Andreas , Hartmann Arndt , Evert Matthias , Märkl Bruno , Bargou Ralf , Mackensen Andreas , Beckmann Matthias W. , Pukrop Tobias , Herr Wolfgang , Einsele Hermann , Trepel Martin , Goebeler Maria-Elisabeth , Claus Rainer , Kerscher Alexander , Lüke Florian
Published: March 2024

Purpose

Offering equal Patient Access to Precision Oncology (PO) is a major challenge of clinical oncologists and cancer center representatives. Here, we provide an easily transferable model adopted from strategic management science to assess the geographic impact of a cancer center – in terms of general cancer care and PO participation.

Methods

As members of the German WERA alliance, the cancer centers Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA’s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care (termed Total Cancer Care, TCC) by WERA. Clustering our outreach along these two dimensions allowed us to set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria and surrounding regions.

Results

In terms of positive MTB and general cancer care referrals, the WERA Matrix overlooked an active screening area of n = 821 postal code areas – representing about 50% of Bavaria’s spatial expansion and more than six million inhabitants. The WERA Matrix identified regions successfully connected to our outreach structures in terms of subsidiarity – with general cancer care mainly performed locally but PO performed in cooperation with WERA. At the same time, we detected postal code areas with a potential PO backlog – characterized by high levels of cancer care performed by WERA and low levels or no MTB representation.

Conclusions

The WERA Matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.
Circulating microvesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus
Authors: Ding Zhe , Qi Fumin , Liu Li , Zhang Na , Lyu Xing , Sun Wenwen , Du Jun , Song Haoming , Hou Hou , Guo Ying , Wang Xiaomei , Liu Ming-Lin , Wei Wei
Published: March 2024

Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Microvesicles (MVs) are known to be associated with thrombosis. Here, we investigated circulating MVs and their associations with SLE-PAH. Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating MVs from leukocytes (LMVs), red blood cells (RMVs), platelets (PMVs), endothelial cells (EMVs), and Annexin V+MVs with phosphatidylserine (PS) exposure. Plasma levels of all MV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+MVs, LMVs, PMVs, RMVs, EMVs, and Annexin V+RMVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LMVs, PMVs, RMVs, Annexin V+MVs, and Annexin V+RMVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+MVs, RMVs, and Annexin V+RMVs. In the SLE-PAH patients, EMVs were positively correlated with pulmonary arterial systolic pressure, while PMVs and EMVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+MVs, LMVs, PMVs, RMVs, EMVs and Annexin V+RMVs can predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LMVs or RMVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Finally, our findings reveal that specific subgroups of circulating MVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LMVs or RMVs may serve as biomarkers for SLE-PAH.
Characterization of maternal mortality and severe maternal morbidity before and during covid-19: an analysis for the Dominican Republic
Authors: Santos-Mercedes Kary Desiree , Coutinho Raquel Zanatta
Published: March 2024

The Covid-19 pandemic disturbed the delivery of health services, which included obstetric care, in many parts of the word. In countries where maternal mortality was already elevated before the pandemic, this disruption brought about catastrophic events. Using data from the Sistema Nacional de Vigilancia Epidemiológica (SINAVE) of the maternal morbidity and mortality of the Dominican Republic, this paper estimated the severe maternal morbidity rate and the maternal mortality rate by causes of death (direct, indirect, and specific causes). Mixed effects models were used to identify individual and contextual factors that contribute to a higher risk of dying. Results indicate that the severe maternal morbidity rate decrease from 12.1 to 10.4 per 1,000 live births in 2020 compared to 2019; however, the maternal mortality rate went from 91.4 to 124.2 per 100,000 live births in the same period. In 2021, a significant increase in morbidity and mortality was observed, registering a rate of 16.5 cases of severe maternal morbidity per 1,000 live births and a rate of 153.7 maternal deaths per 100,000 live births. Additionally, maternal mortality in the Dominican Republic is associated with the sociodemographic and economic conditions of women, revealing inequalities related to national origin, area of residence and access to health services which were worsening during the pandemic.
The protein interactome ofEscherichia colicarbohydrate metabolism
Authors: Chowdhury Shomeek , Fong Stephen S. , Uetz Peter
Published: March 2024

Carbohydrate metabolism is strictly regulated by multiple mechanisms to meet cellular needs (i.e. energy production). Several mechanisms modulate the amount and activity of metabolic enzymes. Here, we investigate how carbohydrate metabolism (CHM) inE. coliis regulated by their interaction properties with other proteins and their quantities. We computationally analyze 378 protein-enzyme interactions (PEIs) potentially involved in carbohydrate metabolism. We identified 20 enzymes and 19 interactors that occur at stoichiometries that are highly likely to affect CHM and 174 interactions that are possibly conserved across thousands of bacteria. These PPIs are predicted to be of global importance, including pathogens.

Author summary

In systems biology, “big” data are used to reconstruct biological networks which are then investigated in detail to uncover their functional dynamics. Understanding functional dynamics finally helps in identifying biomarkers in the big networks. We apply this concept to the biological network which is a crosstalk of protein-protein interaction network and carbohydrate metabolic pathway inEscherichia coliK-12. We investigate if proteins regulate enzymes when they bind them and we predict that protein-enzyme interactions (PEIs) regulate carbohydrate metabolism inE. coli.
A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes inC. elegans
Authors: Binti Shaonil , Linder Adison G. , Edeen Philip T. , Fay David S.
Published: March 2024

Protein tyrosine phosphatases non-receptor type (PTPNs) have been studied extensively in the context of the adaptive immune system; however, their roles beyond immunoregulation are less well explored. Here we identify novel functions for the conservedC. elegansphosphatase PTPN-22, establishing its role in nematode molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen, we found that loss of PTPN-22 phosphatase activity suppressed molting defects caused by loss-of-function mutations in the conserved NIMA-related kinases NEKL-2 (human NEK8/NEK9) and NEKL-3 (human NEK6/NEK7), which act at the interface of membrane trafficking and actin regulation. To better understand the functions of PTPN-22, we carried out proximity labeling studies to identify candidate interactors of PTPN-22 during development. Through this approach we identified the CDC42 guanine-nucleotide exchange factor DNBP-1 (human DNMBP) as an in vivo partner of PTPN-22. Consistent with this interaction, loss of DNBP-1 also suppressednekl-associated molting defects. Genetic analysis, co-localization studies, and proximity labeling revealed roles for PTPN-22 in several epidermal adhesion complexes, includingC. eleganshemidesmosomes, suggesting that PTPN-22 plays a broad role in maintaining the structural integrity of tissues. Localization and proximity labeling also implicated PTPN-22 in functions connected to nucleocytoplasmic transport and mRNA regulation, particularly within the germline, as nearly one-third of proteins identified by PTPN-22 proximity labeling are known P granule components. Collectively, these studies highlight the utility of combined genetic and proteomic approaches for identifying novel gene functions.
Cryptic population structure and insecticide resistance inAnopheles gambiaefrom the southern Democratic Republic of Congo
Authors: Dennis Tristan P.W. , Pescod Poppy , Barasa Sonia , Cerdeira Louise , Lucas Eric R. , Clarkson Chris S. , Miles Alistair , Asidi Alex , Manzambi Emile Z. , Metelo Emery , Zanga Josue , Nsalambi Steve N. , Irish Seth R. , Donnelly Martin James , Agossa Fiacre , Weetman David , Tezzo Francis Wat’senga
Published: March 2024

The Democratic Republic of Congo (DRC) suffers from one of the highest malaria burdens worldwide, but information on itsAnophelesvector populations is relatively limited. Preventative malaria control in DRC is reliant on pyrethroid-treated nets, raising concerns over the potential impacts of insecticide resistance. We sampledAnopheles gambiaefrom three geographically distinct populations (Kimpese, Kapolowe and Mikalayi) in southern DRC, collecting from three sub-sites per population and characterising mosquito collections from each for resistance to pyrethroids using WHO tube bioassays. Resistance to each of three different pyrethroids was generally high inAn. gambiaewith <92% mortality in all tests, but varied between collections, with mosquitoes from Kimpese being the most resistant.

Whole genome sequencing of 165An. gambiaerevealed evidence for genetic differentiation between Kimpese and Kapolowe / Mikalayi, but not between the latter two sample sites despite separation of approximately 800km. Surprisingly, there was evidence of population structure at a small spatial scale between collection subsites in Kimpese, despite separation of just tens of kilometres. Intra-population (H12) and inter-population (FST) genome scans identified multiple peaks corresponding to genes associated with insecticide resistance such as the voltage gated sodium channel (Vgsc)target site on chromosome 2L, aCyp6cytochrome P450 cluster on chromosome arm 2R, and theCyp9k1P450 gene on chromosome X. In addition, in the Kimpese subsites, the P450 redox partner geneCprshowed evidence for contemporary selection (H12) and population differentiation (FST) meriting further exploration as a potential resistance associated marker.
The Pivotal Involvement of theRespiratory burst oxidase G(SlRbohG) Gene in H2O2Production Under Stress for Proper Na+Homeostasis Regulation in Tomato
Authors: Egea I , Barragán-Lozano T , Estrada Y , Jáquez-Gutiérrez M , Plasencia FA , Atarés A , Garcia-Sogo B , Capel C , Yuste-Lisbona F , Egea-Sánchez JM , Flores FB , Angosto T , Moreno M , Lozano R , Pineda B
Published: March 2024

Regulation of sodium homeostasis is crucial for plant response to salinity conditions. Here we report on the genetic and physiological characterization of two tomato allelic mutants,sodiumgatherer1-2(sga1-2), which exhibit pronounced chlorosis and hyperhydration under salt stress. Mapping-by-sequencing revealed that mutant phenotype resulted from mutations in theSlRbohGgene, and CRISPR/Cas9 knockouts of this gene gave phenocopies of thesga1-2mutants. Physiological analyses showed thatsga1-2salt hypersensitivity is linked to an increase of Na+and water transport from roots to shoots, which explains their extreme chlorosis and hyperhydration under salinity conditions. At the molecular level,SlPIP2;12gene, an aquaporin down-regulated in the WT under salt stress, was overexpressed in thesga1-2mutants, which could enhance water transport to the shoot. Also,sga1-2mutants exhibited a significant reduction in the expression of key sodium transporters, thus modifying the normal distribution of Na+in tomato plant tissues. Furthermore, treatment of WT plants with the NADPH oxidase inhibitor DPI prevented H2O2production in response to salinity, resulting in elevated Na+accumulation in the shoot and reduced expression of theSlHKT1;2gene in root. Altogether, our results show thatSlRbohGplays a central role in salt tolerance through ROS-mediated signaling.

HIGHLIGHT

Loss of function of tomatoSlRbohGgene leads hypersensibility to salt stress due to increased Na+and water transport from root to shoot.