bluuebunny/crossref_metadata_2025 huggingface dataset:
Health care accessibility and mobility in breast cancer: a Latin American perspective
Authors: Azeredo-da-Silva André Ferreira , Zanotto Bruna Stella , Martins Flavia , Navarro Nádia , Alencar Rafaela , Medeiros Clarissa
Published: June 2024

Background

Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant socioeconomic and ethno-racial disparities persist in health care access across the region. Breast cancer (BC) incidence and mortality rates in Brazil are comparable to those in other LATAM countries, supporting the relevance of Brazilian data, with Brazil’s health care policies and expenditures often serving as models for neighboring countries. We evaluated the impact of mobility on oncological outcomes in LATAM by analyzing studies of patients with BC reporting commuting routes or travel distances to receive treatment or diagnosis.

Methods

We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, LILACS, and Google Scholar databases. Studies eligible for inclusion were randomized controlled trials and observational studies of patients with BC published in English, Portuguese, or Spanish and conducted in LATAM. The primary outcome was the impact of mobility or travel distance on oncological outcomes. Secondary outcomes included factors related to mobility barriers and access to health services. For studies meeting eligibility, relevant data were extracted using standardized forms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Quantitative and qualitative evidence synthesis focused on estimating travel distances based on available data. Heterogeneity across distance traveled or travel time was addressed by converting reported travel time to kilometers traveled and estimating distances for unspecified locations.

Results

Of 1142 records identified, 14 were included (12 from Brazil, 1 from Mexico, and 1 from Argentina). Meta-analysis revealed an average travel distance of 77.8 km (95% CI, 49.1-106.48) to access BC-related diagnostic or therapeutic resources. Nonetheless, this average fails to precisely encapsulate the distinct characteristics of each region, where notable variations persist in travel distance, ranging from 88 km in the South to 448 km in the North.

Conclusion

The influence of mobility and travel distance on access to BC care is multifaceted and should consider the complex interplay of geographic barriers, sociodemographic factors, health system issues, and policy-related challenges. Further research is needed to comprehensively understand the variables impacting access to health services, particularly in LATAM countries, where the challenges women face during treatment remain understudied.

Trial registration

CRD42023446936.
Integration of large and diverse angiosperm DNA fragments into Asian Gnetum mitogenomes
Authors: Wu Chung-Shien , Wang Rui-Jiang , Chaw Shu-Miaw
Published: June 2024

Background

Horizontal gene transfer (HGT) events have rarely been reported in gymnosperms. Gnetum is a gymnosperm genus comprising 25‒35 species sympatric with angiosperms in West African, South American, and Southeast Asian rainforests. Only a single acquisition of an angiosperm mitochondrial intron has been documented to date in Asian Gnetum mitogenomes. We wanted to develop a more comprehensive understanding of frequency and fragment length distribution of such events as well as their evolutionary history in this genus.

Results

We sequenced and assembled mitogenomes from five Asian Gnetum species. These genomes vary remarkably in size and foreign DNA content. We identified 15 mitochondrion-derived and five plastid-derived (MTPT) foreign genes. Our phylogenetic analyses strongly indicate that these foreign genes were transferred from diverse eudicots—mostly from the Rubiaceae genus Coptosapelta and ten genera of Malpighiales. This indicates that Asian Gnetum has experienced multiple independent HGT events. Patterns of sequence evolution strongly suggest DNA-mediated transfer between mitochondria as the primary mechanism giving rise to these HGT events. Most Asian Gnetum species are lianas and often entwined with sympatric angiosperms. We therefore propose that close apposition of Gnetum and angiosperm stems presents opportunities for interspecific cell-to-cell contact through friction and wounding, leading to HGT.

Conclusions

Our study reveals that multiple HGT events have resulted in massive amounts of angiosperm mitochondrial DNA integrated into Asian Gnetum mitogenomes. Gnetum and its neighboring angiosperms are often entwined with each other, possibly accounting for frequent HGT between these two phylogenetically remote lineages.
M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis
Authors: Zhu Xiaolan , Li Wenxin , Lu Minjun , Shang Junyu , Zhou Jiamin , Lin Li , Liu Yueqin , Xing Jie , Zhang Mengxue , Zhao Shijie , Lu Jingjing , Shi Xuyan
Published: June 2024

Background

Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.

Methods

A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.

Results

Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.

Conclusion

H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.

Graphical Abstract
Oncological outcomes of fertility-sparing surgery versus radical surgery in stage - epithelial ovarian cancer: a systematic review and meta-analysis
Authors: Guan Ziting , Zhang Changlin , Lin Xinmei , Zhang Jingwei , Li Tian , Li Jundong
Published: June 2024

Background

The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS.

Methods

We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460).

Results

From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04).

Conclusions

This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway
Authors: Ni Biyan , Yang Ziqi , Zhou Tian , Zhou Hong , Zhou Yang , Lin Shiya , Xu Huiyi , Lin Xiaojing , Yi Wei , He Chang , Liu Xialin
Published: June 2024

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.
Support for sexual and reproductive health and rights in Sub-Saharan Africa: a new index based on World Values Survey data
Authors: Svallfors Signe , Båge Karin , Ekström Anna Mia , Dessie Yadeta , Wado Yohannes Dibaba , Fagbemi Mariam , Larsson Elin C. , Litorp Helena , Puranen Bi , Sundewall Jesper , Uthman Olalekan A. , Kågesten Anna E.
Published: June 2024

Background

Addressing attitudes is central to achieving sexual and reproductive health and rights (SRHR) and Agenda 2030. We aimed to develop a comprehensive index to measure attitudinal support for SRHR, expanding opportunities for global trend analyses and tailored interventions.

Methods

We designed a new module capturing attitudes towards different dimensions of SRHR, collected via the nationally representative World Values Survey in Ethiopia, Kenya, and Zimbabwe during 2020–2021 (n = 3,711). We used exploratory factor analysis of 58 items to identify sub-scales and an overall index. Adjusted regression models were used to evaluate the index according to sociodemographic characteristics, stratified by country and sex.

Results

A 23-item, five-factor solution was identified and used to construct sub-indices reflecting support for: (1) sexual and reproductive rights, (2) neighborhood sexual safety, (3) gender-equitable relationships, (4) equitable masculinity norms, and (5) SRHR interventions. These five sub-indices performed well across countries and socioeconomic subgroups and were combined into a comprehensive “SRHR Support Index”, standardized on a 1–100 scale (mean = 39.19, SD = 15.27, Cronbach’s alpha = 0.80) with higher values indicating more support for SRHR. Mean values were highest in Kenya (45.48, SD = 16.78) followed by Ethiopia (40.2, SD = 13.63), and lowest in Zimbabwe (32.65, SD = 13.77), with no differences by sex. Higher education and being single were associated with more support, except in Ethiopia. Younger age and urban residence correlated with more support among males only.

Conclusion

The SRHR Support Index has the potential to broaden SRHR attitude research from a comprehensive perspective – addressing the need for a common measure to track progress over time.
Virological outcomes of third-line antiretroviral therapy in a global context: a systematic reviews and meta-analysis
Authors: kitaw Tegene Atamenta , Abate Biruk Beletew , Yilak Gizachew , Tilahun Befkad Derese , Faris Abebe Merchaw , Walle Getachew Tesfaw , Haile Ribka Nigatu
Published: June 2024

Background

Despite remarkable progress, HIV’s influence on global health remains firm, demanding continued attention. Understanding the effectiveness of third-line antiretroviral therapy in individuals who do not respond to second-line drugs is crucial for improving treatment strategies. The virological outcomes of third-line antiretroviral therapy vary from study to study, highlighting the need for robust global estimates.

Methods

A comprehensive search of databases including PubMed, MEDLINE, International Scientific Indexing, Web of Science, and Google Scholar, was conducted. STATA version 17 statistical software was used for analysis. A random-effects model was applied to compute the pooled estimates. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also performed. The prediction interval is computed to estimate the interval in which a future study will fall. The GRADE tool was also used to determine the quality of the evidence.

Results

In this systematic review and meta-analysis, 15 studies involving 1768 HIV patients receiving third-line antiretroviral therapy were included. The pooled viral suppression of third-line antiretroviral therapy was 76.6% (95% CI: 71.5- 81.7%). The viral suppression rates at 6 and 12 months were 75.5% and 78.6%, respectively. Furthermore, third-line therapy effectively suppressed viral RNA copy numbers to ≤ 50 copies/mL, ≤ 200 copies/mL, and ≤ 400 copies/mL with rates of 70.7%, 85.4%, and 85.7%, respectively.

Conclusion

More than three-fourths of patients on third-line antiretroviral therapy achieve viral suppression. Consequently, improving access to and timely initiation of third-line therapy may positively impact the quality of life for those with second-line treatment failure.
From asymptomatic adult patient to cardiopulmonary resuscitation – treatment of ALCAPA with total arterial myocardial revascularisation and mitral valve repair
Authors: Al-Obaidi Mustafa , Hecker Florian , Walther Thomas , Holubec Tomas
Published: June 2024

Background

Anomalous left coronary artery originating from the pulmonary artery (ALCAPA), is a unique congenital anomaly, comprising only 0.24–0.46% of all congenital cardiac anomalies. Late presentations, ranging from asymptomatic cases to sudden cardiac arrest, are exceptionally rare. This unique case highlights the complexity of managing ALCAPA in adulthood and underscores the necessity of a comprehensive surgical approach addressing both coronary and valvular issues.

Presentation

A 34-year-old female patient, who had been diagnosed with ALPACA in her early childhood, suffered sudden cardiac arrest at work, followed by out-of-hospital resuscitation. The patient had been followed-up regularly until adolescence, however, she had refused surgery. In the diagnostic work-up following successful resuscitation severe mitral valve regurgitation was additionally revealed. Subsequently, the patient underwent surgery, involving coronary artery bypass grafting (CABG), using bilateral internal mammary arteries, and mitral valve repair, with an excellent postsurgical result. At 16-month follow-up, the patient was asymptomatic and quality of life had significantly improved.

Conclusion

This rare case initially presented as silent myocardial ischemia, resulting in reduced left ventricular function and secondary mitral incompetence. Surgical treatment of ALCAPA in adults poses greater challenges and a higher risk than in children. CABG procedure offers an excellent prognostic therapeutic strategy, since this procedure is a routine in adult cardiac surgery.
Construction of prediction models for novel subtypes in patients with arteriosclerosis obliterans undergoing endovascular therapy: an unsupervised machine learning study
Authors: Li Xiaocheng , Zhang Lin , Li Que , Zhang Jiangfeng , Qin Xiao
Published: June 2024

Background

Arteriosclerosis obliterans (ASO) is a chronic arterial disease that can lead to critical limb ischemia. Endovascular therapy is increasingly used for limb salvage in ASO patients, but the outcomes vary. The development of prediction models using unsupervised machine learning may lead to the identification of novel subtypes to guide patient prognosis and treatment.

Methods

This retrospective study analyzed clinical data from 448 patients with ASOs who underwent endovascular therapy. Unsupervised machine learning algorithms were employed to identify subgroups. To validate the precision of the clustering outcomes, an analysis of the postoperative results of the clusters was conducted. A prediction model was constructed using binary logistic regression.

Results

Two distinct subgroups were identified by unsupervised machine learning and characterized by differing patterns of clinical features. Patients in Cluster 2 had significantly worse conditions and prognoses than those in Cluster 1. For the novel ASO subtypes, a nomogram was developed using six predictive factors, namely, platelet count, ankle brachial index, Rutherford category, operation method, hypertension, and diabetes status. The nomogram achieved excellent discrimination for predicting membership in the two identified clusters, with an area under the curve of 0.96 and 0.95 in training cohort and internal test cohort.

Conclusion

This study demonstrated that unsupervised machine learning can reveal novel phenotypic subgroups of patients with varying prognostic risk who underwent endovascular therapy. The prediction model developed could support clinical decision-making and risk counseling for this complex patient population. Further external validation is warranted to assess the generalizability of the findings.
Splice_sim: a nucleotide conversion-enabled RNA-seq simulation and evaluation framework
Authors: Popitsch Niko , Neumann Tobias , von Haeseler Arndt , Ameres Stefan L.
Published: June 2024

Nucleotide conversion RNA sequencing techniques interrogate chemical RNA modifications in cellular transcripts, resulting in mismatch-containing reads. Biases in mapping the resulting reads to reference genomes remain poorly understood. We present splice_sim, a splice-aware RNA-seq simulation and evaluation pipeline that introduces user-defined nucleotide conversions at set frequencies, creates mixture models of converted and unconverted reads, and calculates mapping accuracies per genomic annotation. By simulating nucleotide conversion RNA-seq datasets under realistic experimental conditions, including metabolic RNA labeling and RNA bisulfite sequencing, we measure mapping accuracies of state-of-the-art spliced-read mappers for mouse and human transcripts and derive strategies to prevent biases in the data interpretation.
De novo biosynthesis of β-arbutin in Corynebacterium glutamicum via pathway engineering and process optimization
Authors: Zhang Bin , Gou Kexin , Xu Kexin , Li Zhimin , Guo Xiaoyan , Wu Xiaoyu
Published: June 2024

Background

β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin.

Results

This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium.

Conclusions

This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.
Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report
Authors: Jafari-Nozad Amir Masoud , Jahani Najmeh , Moniri Yoones
Published: June 2024

Background

Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.

Case presentation

We report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.

Conclusion

Ovarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.
Temporal trends of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus in Gabon
Authors: Gouleu Christiane Sidonie , Daouda Maradona Agbanrin , Oye Bingono Sam O’neilla , McCall Matthew Benjamin Bransby , Alabi Abraham Sunday , Adegnika Ayola Akim , Schaumburg Frieder , Grebe Tobias
Published: June 2024

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of mortality due to bacterial antimicrobial resistance. While S. aureus is common in skin and soft tissue infections (SSTI) in Africa, data on MRSA rates are scarce and reports vary widely across the continent (5%-80%). In this study, we describe the proportion of MRSA causing SSTI in Lambaréné, Gabon, over an 11-year period.

Methods

We retrospectively analyzed data from 953 bacterial specimens collected from inpatients and outpatients with SSTI at the Albert Schweitzer Hospital, Lambaréné, Gabon, between 2009 and 2019. We determined temporal changes in the prevalence of MRSA and identified risk factors for SSTI with MRSA.

Results

68% of all specimens with bacterial growth yielded S. aureus (n = 499/731), of which 7% (36/497) with antimicrobial susceptibility testing were identified as MRSA. Age above 18 years, admission to the surgical ward, and deep-seated infections were significantly associated with MRSA as the causative agent. After an initial decline from 7% in 2009, there was a marked increase in the proportion of MRSA among all S. aureus from SSTI from 3 to 20% between 2012 and 2019. The resistance rate to erythromycin was significantly higher in MRSA than in methicillin-susceptible S. aureus (73% vs. 10%), and clindamycin resistance was detected exclusively in MRSA isolates (8%).

Conclusion

The increasing proportion of MRSA causing SSTI over the 11-year period contrasts with many European countries where MRSA is on decline. Continuous surveillance of MRSA lineages in the hospital and community along with antibiotic stewardship programs could address the increasing trend of MRSA.
Intracerebral haemorrhage in multiple sclerosis: assessing the impact of disease-modifying medications
Authors: Ou Yong Brian M. , Awuah Wireko Andrew , Shah Muhammad Hamza , Sanker Vivek , Huk Jonathan Kong Sing , Venkata Sujashree Yadala , Patel Diti H. , Tan Joecelyn Kirani , Khan Noor Ayman , Kulasekaran Ajitha , Sarkar Manali , Abdul-Rahman Toufik , Atallah Oday
Published: June 2024

Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments.
Metagenomic insights into microbial adaptation to the salinity gradient of a typical short residence-time estuary
Authors: Wu Ziheng , Li Minchun , Qu Liping , Zhang Chuanlun , Xie Wei
Published: June 2024

Background

Microbial adaptation to salinity has been a classic inquiry in the field of microbiology. It has been demonstrated that microorganisms can endure salinity stress via either the “salt-in” strategy, involving inorganic ion uptake, or the “salt-out” strategy, relying on compatible solutes. While these insights are mostly based on laboratory-cultured isolates, exploring the adaptive mechanisms of microorganisms within natural salinity gradient is crucial for gaining a deeper understanding of microbial adaptation in the estuarine ecosystem.

Results

Here, we conducted metagenomic analyses on filtered surface water samples collected from a typical subtropical short residence-time estuary and categorized them by salinity into low-, intermediate-, and high-salinity metagenomes. Our findings highlighted salinity-driven variations in microbial community composition and function, as revealed through taxonomic and Clusters of Orthologous Group (COG) functional annotations. Through metagenomic binning, 127 bacterial and archaeal metagenome-assembled genomes (MAGs) were reconstructed. These MAGs were categorized as stenohaline—specific to low-, intermediate-, or high-salinity—based on the average relative abundance in one salinity category significantly exceeding those in the other two categories by an order of magnitude. Those that did not meet this criterion were classified as euryhaline, indicating a broader range of salinity tolerance. Applying the Boruta algorithm, a machine learning-based feature selection method, we discerned important genomic features from the stenohaline bacterial MAGs. Of the total 12,162 COGs obtained, 40 were identified as important features, with the “inorganic ion transport and metabolism” COG category emerging as the most prominent. Furthermore, eight COGs were implicated in microbial osmoregulation, of which four were related to the “salt-in” strategy, three to the “salt-out” strategy, and one to the regulation of water channel activity. COG0168, annotated as the Trk-type K+ transporter related to the “salt-in” strategy, was ranked as the most important feature. The relative abundance of COG0168 was observed to increase with rising salinity across metagenomes, the stenohaline strains, and the dominant Actinobacteriota and Proteobacteria phyla.

Conclusions

We demonstrated that salinity exerts influences on both the taxonomic and functional profiles of the microbial communities inhabiting the estuarine ecosystem. Our findings shed light on diverse salinity adaptation strategies employed by the estuarine microbial communities, highlighting the crucial role of the “salt-in” strategy mediated by Trk-type K+ transporters for microorganisms thriving under osmotic stress in the short residence-time estuary.
Surgical treatment of appendiceal mucormycosis in an immunocompromised patient: a case report
Authors: Orihara Yukiya , Kurahashi Shingo , Kamei Katsuhiko , Hiramatsu Kazuhiro
Published: June 2024

Background

Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to antifungal therapy, is essential. Herein, we describe the successful management of appendiceal mucormycosis in a patient with acute promyelocytic leukemia through rapid surgical intervention and antifungal therapy.

Case presentation

A 29-year-old woman underwent autologous peripheral blood stem cell transplantation for acute promyelocytic leukemia (APL). Subsequently, her condition relapsed, and remission induction therapy was initiated. During the immunosuppressive period, she developed a fever and severe abdominal pain. Computed tomography revealed severe edema of the ileum, cecum, and ascending colon. Despite receiving multiple antibiotics, antivirals, and antifungals, her condition showed no improvement. Consequently, she underwent exploratory laparotomy, with no bowel perforation noted, revealing severe inflammation in the ileum, cecum, and ascending colon, as well as appendiceal necrosis. Appendectomy was performed, and histopathological analysis revealed hyphae in the vessels and layers of the appendiceal wall, suggestive of mucormycosis. The patient was diagnosed with appendiceal mucormycosis, and liposomal amphotericin B was administered. Subsequent monitoring showed no recurrence of mucormycosis. Genetic analysis of the resected tissue revealed Rhizopus microspores as the causative agent.

Conclusions

Rapid surgical intervention and antifungal drug administration proved successful in managing appendiceal mucormycosis in a patient with APL. Early recognition and aggressive surgical intervention are imperative to improve outcomes in such patients.
The repository of biocontrol agents for Spodoptera frugiperda (Smith, 1797) with emphasis on their mode of action
Authors: Mahmood Samar , Parwez Hina
Published: June 2024

Background

Spodoptera frugiperda(Smith, 1797) is one of the most destructive pests of Maize plants, causing an estimated 40% crop loss in 2019. It is a native pest of America and difficult to control since it has developed resistance against most insecticides efficient in controlling lepidopteran pests, including recommended Chlorantraniliprole and Flubendiamide. Due to the increasing need for a change in pest management methods, it is necessary to consider biological control on a commercial level.

Main body

In this review, we have put together a list of all the biocontrol agents (parasites, parasitoids, predators, viruses, bacteria, and fungi) reported from different parts of the world effective in managing the impact ofS. frugiperda, along with an elaborate mechanism of action of each natural killer. After analyzing the procured data, Pareto charts were prepared plotting the distribution of the mortality ofS. frugiperdacaused by parasitoids and pathogens. The regional abundance was plotted in the form of graph.

Conclusion

Pareto’s charts (Fig. 6) shows thatTelenomus remusandSteinernema riobraveaccounts for a maximum of 90% mortality ofS. frugiperdaamong other high contributors (Chelonus insularis, Trichospilus pupivora, Ophion flavidus, Heterorhabditis indica, Heterorhabditis bacteriophora, Trichogramma mwanai). NPV andMetarhizium anisopliaewere proved to be the most effective micro-entomopathogens causing up to 98% mortality. Also, these entomopathogens were reported all over the world but found abundant in Mexico and India. Based on this study, we recommend the augmentation of entomopathogenic insects on a large scale only to commercialize them in the market and produce different ready-to-use pathogenic formulations to be applied in the fields combined with a significantly less quantity of harmful chemical ailments.
Parents reported language development and scholastic achievement in children with congenital heart diseases versus typically developed
Authors: Almuzaini Hanan I. , Almuzaini Ibrahim , Hassan Megahed Mohamed
Published: June 2024

Background

Children with congenital heart diseases (CHD) may have developmental delays including delayed language development (DLD) and learning difficulties. The purpose of this study was to observe the effects of CHD on language developmental profile and scholastic achievement (SA) with particular emphasis on prevalence of DLD and SA, potential risks, and need for early intervention.

Results

This case–control study included 158 children with CHD and 145 healthy children as controls. Participants’ ages ranged from 6 months to 15 years. Data were collected by reviewing clinical records and questionnaires covering potential risks, motor and language development, and SA. Potential risks were analyzed using the Fisher test, while language development and SA were compared using Mann–Whitney test. The incidences of parent consanguinity, family history of DLD, and neonatal cyanosis were higher than expected by chance in the CHD group with p-values which are < 0.001, 0.044, and < 0.001, respectively. The CHD group revealed more delay in babbling, first word production, two-word sentences, three-word sentences, narration, and SA than control group with significant differences. These comparisons’ p-values are 0.002, < 0.001, 0.009, 0.029, 0.03, and 0.042 respectively with mean effect size 0.3. The language development profile in cyanotic HD showed more delay than acyanotic HD with significant differences.

Conclusions

The DLD and affected SA were more prevalent in children with CHD. The risk for DLD in CHD children was multifactorial; however, the main predisposing factor was chronic hypoxia that starts in the intrauterine life in CHD. Neonates with CHD require early intervention through oxygen therapy before surgery. Early family counseling and language therapy are recommended to improve quality of life through achieving better communicative ability and academic skills. Further studies which concerned the effect of maternal oxygenation on prognosis of fetuses with CHD may be required. Also, duplication of the study including formal testing is recommended.
US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy
Authors: Duke Elizabeth S. , Bradford Diana , Sinha Arup K. , Mishra-Kalyani Pallavi S. , Lerro Catherine C. , Rivera Donna , Wearne Emily , Miller Claudia P. , Leighton John , Sabit Hairat , Zhao Hong , Lane Ashley , Scepura Barbara , Pazdur Richard , Singh Harpreet , Kluetz Paul G. , Donoghue Martha , Drezner Nicole
Published: June 2024

On December 13, 2023, the US Food and Drug Administration (FDA) approved eflornithine (IWILFIN, US WorldMeds) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. The approval was based on an externally controlled trial (ECT) consisting of a single-arm trial, study 3(b), compared with an external control (EC) derived from a National Cancer Institute/Children's Oncology Group–sponsored clinical trial (Study ANBL0032) and supported by confirmatory evidence. In the protocol-specified primary analysis, the event-free survival hazard ratio (HR) was 0.48 (95% CI, 0.27 to 0.85) and overall survival HR was 0.32 (95% CI, 0.15 to 0.70). The most common adverse reactions (≥5%) were hearing loss, otitis media, pyrexia, pneumonia, and diarrhea. Notably, this is the first oncology drug approval which relies on an ECT as the primary clinical data to support substantial evidence of effectiveness. This was made possible by a distinctly high-quality, comparable EC data set with consistent treatment effect estimations demonstrated in multiple sensitivity and supportive analyses. Eflornithine's manageable safety profile and strong nonclinical and mechanistic data provided further support for the approval, and the evidentiary package was evaluated in the context of high unmet need in a rare, life-threatening cancer.
Preventing Infection in Pediatric Patients Receiving Chemotherapy: A Survey of Provider Recommendations
Authors: Offenbacher Rachel , Citron Chloe , Lin Juan , Hosgood H. Dean , Parsons Susan K. , Moerdler Scott , Weiser Daniel A.
Published: June 2024

PURPOSE

Sepsis is the leading cause of mortality in patients with childhood cancer receiving cytotoxic chemotherapy. Pediatric hematology/oncology and transplant (PHOT) providers must counsel their patients on the safety of public activities and weigh the risk of infection exposure with the social and developmental benefits of in-person school and social outings. We hypothesize that there is significant variability in recommendations given by PHOT providers.

METHODS

An electronic anonymous survey was developed and piloted by a group of PHOT providers to assess current methods for educating patients and families on limiting infectious exposures. Five clinical vignettes were created by the study team to explore how providers balance the competing priorities of safety and health-related quality of life (HRQoL). The electronic survey was institutional review board–approved and disseminated via email to all PHOT providers affiliated with the Children's Oncology Group across the United States.

RESULTS

In total, 545 clinicians completed the survey. Most respondents were attending physicians (393, 72%), followed by fellows (61, 11%), advanced practice providers (APPs; 38, 7%), and nurses (37, 7%). On average, nurses and fellows made more conservative recommendations for avoiding infectious exposures compared with the recommendations from attending physicians and APPs (
P
< .0001). On average, providers with more years of clinical experience expressed less cautious recommendations, whereas those with less years of experience provided more cautious recommendations for avoiding infectious exposures (
P
= .0072).

CONCLUSION

This survey demonstrates the importance of collaboration between all members of the care team in defining priorities for balancing safety risk and HRQoL to provide consistent messaging to patients. The variations in survey responses highlight the need for universal guidelines to standardize physician recommendations for limiting infectious exposures in pediatric patients on chemotherapy.
Availability of Cranial Prostheses for Black Patients at Comprehensive Cancer Centers
Authors: Minta Abena , Rose Lucy , Shareef Sarah J. , Adame Stephanie , Dulmage Brittany
Published: June 2024

PURPOSE

For patients who seek to camouflage cancer-related hair loss, cranial prostheses such as wigs and hair pieces exist. We sought to determine the availability of yaki-textured, type IV curls, and afro wigs at boutiques in Comprehensive Cancer Centers (CCCs).

METHODS

The 56 CCCs in the United States were surveyed to see whether they had an affiliated wig boutique for patients experiencing hair loss. Boutique workers were then asked a series of seven questions regarding cranial prostheses options for patients seeking yaki-textured, type IV curls, and afro wigs. The availability of wigs was compared with US Census data on population size and density of Black residents.

RESULTS

Of the 56 CCCs, 27 (46%) institutions had active affiliated hair boutiques. We were able to reach 19 (70%) of the 27 boutiques, of which 53% (n = 10) offered yaki-textured wigs, 37% (n = 7) offered type IV curls or afro wigs, and 47% (n = 9) offered neither. Two additional boutiques offered in-store catalogs for Black patients who were interested in naturally appearing wigs. Although two institutions offered a wig bank that was free to all patients, neither had yaki-textured or afro wigs in stock. There was no significant relationship between population size or density of Black residents and availability of these wigs.

CONCLUSION

Many Black patients undergoing cancer treatment interested in cranial prosthesis do not have consistent access to wigs with textures comparable with type IV hair at CCCs. With increased inventory of racially inclusive wigs, partnerships with third-party vendors, and support for the previous authorization process, we can better support Black patients experiencing cancer-related hair loss.
Opportunistic Detection of Phytosterolemia During Genetic Testing for FH: Case Series and Contextual Review
Authors: Loh Wann Jia , Chan Dick C , Pang Jing , Hooper Amanda J , Bell Damon , Watts Gerald F
Published: June 2024

Background

Homozygous phytosterolemia is a rare autosomal recessive disorder that leads to severely elevated plasma levels of plant phytosterols, causing an increased risk of coronary artery disease (CAD) and mimicking the clinical presentation of familial hypercholesterolemia (FH). Integration of the genetic variants for homozygous phytosterolemia into the genetic panel for FH in clinical practice likely increases the detection of milder genetic forms of phytosterolemia, the implications of which in clinical practice, including cascade testing, remain unclear.

Results

We report 3 families with pathogenic loss-of-function variants in ABCG5 and/or ABCG8, in which probands were identified incidentally when genetically testing them for FH. The proband of the first family was a 35-year-old man with a homozygous ABCG5 loss-of-function variant (c.1336C > T, p.Arg446*) causing severe phytosterolemia and premature CAD on cardiac imaging; his younger brother was heterozygous for the same variant with mildly elevated phytosterol levels. The second family included 2 sisters (aged 31 and 29 years) with digenic variants in ABCG5 (c.1336C > T, p.Arg446*) and ABCG8 (c.1269G > T, p.Glu423Asp with uncertain significance) with moderately elevated plasma phytosterol levels and premature CAD on cardiac imaging. The third family is a 68-year-old man and his 44-year-old daughter who were both heterozygous for a pathogenic ABCG5 variant (c.1166G > A, p.Arg389His) that had mild phytosterolemia and CAD on cardiac imaging. Treatment with ezetimibe alone or in combination with colesevelam reduced elevated plasma sitosterol and campesterol concentrations by 30% to 80%.

Conclusion

Phytosterolemia is specific genetic disorder that can mimic FH, cause premature atherosclerosis, and require specific pharmacotherapy. Cascade testing for pathogenic ABCG5/G8 variants can lead to earlier detection and treatment of affected family members.
Loss-of-function Thr347Ala Variant in the G Protein Subunit-Α11 Causes Familial Hypocalciuric Hypercalcemia 2
Authors: Boisen Ida Marie , Du Wei , Juul Anders , Bräuner-Osborne Hans , Jensen Anders A , Blomberg Jensen Martin
Published: June 2024

Context and Objectives

To date, only 4 loss-of-function variants in the GNA11 gene encoding the G protein subunit α11 (Gα11) leading to familial hypocalciuric hypercalcemia (FHH) 2 have been characterized. Gα11 is involved in calcium-sensing receptor (CaSR) signaling, and loss-of-function variants in GNA11 lead to reduced agonist potency at CaSR and an FHH phenotype.

Design and participants

We have identified a family with a heterozygous GNA11 Thr347Ala variant and characterized its impact on calcium homeostasis in FHH2 patients and the signaling properties of CaSR through the Gα11-Thr347Ala variant in vitro.

Main Outcome Measures

The index patient and her family had clinical, biochemical, and genetic analyses performed. The expression levels of Gα11 and the cell-surface expression levels of CaSR in human embryonic kidney 293A Gq/11 knockout cells (ΔGq/11-HEK293A) cotransfected with CaSR and Gα11 [wild type (WT) or Thr347Ala] were determined, and the functional properties exhibited by calcium at CaSR were characterized in an inositol monophosphate (IP1) accumulation assay.

Results

Heterozygous carriers of the GNA11 Thr347Ala variant had mild asymptomatic hypercalcemia, hypocalciuria, and inappropriately high normal PTH levels considering their elevated serum calcium levels. Whereas the variant did not impact Gα11 expression or CaSR cell surface expression levels, calcium displayed a moderately but significantly lower agonist potency at CaSR/Gα11-Thr347Ala-transfected cells compared with CaSR/Gα11-WT-transfected cells in the IP1 accumulation assay (EC50 values of 5.67 mM and 4.38 mM, respectively).

Conclusion

This identification of a novel GNA11 variant causing FHH2 substantiates the important role of Gα11 for CaSR signaling and Ca2+ homeostasis.