bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Diagnosis of impaired consciousness in a cancer patient using immune checkpoint inhibitors
Authors: Cathalifaud Daniel , Basáez Cristóbal , Yáñez Tatiana
Published: January 2025

Immune checkpoint inhibitors (ICIs) are drugs that are being increasingly used in the field of oncology; due to their mechanism of action, they can present immune-related adverse effects (IRAEs), with various clinical manifestations, one of which is delirium. We present the case of a patient diagnosed with pleural mesothelioma that started combined palliative immunotherapy two months before admission. She was hospitalized for delirium with psychotic symptoms and a comprehensive neurological and etiological examination for this pathology was performed, revealing undetectable TSH levels, indicating the etiology of the condition as thyrotoxicosis in the context of autoimmune thyroiditis, secondary to treatment with ICIs. Symptomatic treatment with beta-blockers was initiated, leading to progressive improvement. This case brings awareness of impaired consciousness and neuropsychiatric symptoms as manifestation of IRAEs and the difficulty of their diagnosis: there may also be several other causes of impaired consciousness, so the characterization of delirium requires a multifaceted approach to determine the underlying cause, taking into account direct cancer-related complications and those stemming from the treatments received by this group of patients. Endocrinological immune-related adverse events (IRAEs), such as thyroid IRAEs, generally have a low lethality rate, do not necessarily require discontinuation of therapy, and are linked to a more favorable oncological prognosis. Conversely, neurological IRAEs, though rare, constitute a contraindication for further use of ICIs. This clinical case emphasizes the importance of the systematic study of consciousness impairment in cancer patients, and of considering multiple IRAEs that could lead to changes in oncological therapy when establishing possible etiologies.
CD94-driven in vitro expansion of highly functional adaptive NKG2C+ NKG2A- CD57+ NK cells from CMV+ healthy donors
Authors: Giordano Chiara , Carlomagno Simona , Falco Michela , Cantoni Claudia , Vitale Massimo , Caruana Ignazio , Dirks Johannes , Serio Alberto , Muccio Letizia , Bartalucci Giulia , Bo Alessandra , Locatelli Franco , Bottino Cristina , Sivori Simona , Della Chiesa Mariella
Published: January 2025

Background

Adaptive human natural killer (NK) cells are an NK cell subpopulation arising upon cytomegalovirus (CMV) infection. They are characterized by CD94/NKG2C expression, a mature CD57+KIR+NKG2A– phenotype, a prolonged lifespan, and remarkable antitumor functions. In light of these features, adaptive NK cells represent suitable candidate to design next-generation therapies, based on their enhanced effector function which could be further boosted by Chimeric Antigen Receptors-engineering, or the combination with cell engagers. For therapeutic approaches, however, it is key to generate large numbers of functional cells.

Purpose

We developed a method to efficiently expand adaptive NK cells from NK-enriched cell preparations derived from the peripheral blood of selected CMV-seropositive healthy donors. The method is based on the use of an anti-CD94 monoclonal antibody (mAb) combined with IL-2 or IL-15.

Results

By setting this method we were able to expand high numbers of NK cells showing the typical adaptive phenotype, CD94/NKG2C+ CD94/NKG2A- CD57+, and expressing a single self-inhibitory KIR. Expanded cells maintained the CMV-induced molecular signature, exhibited high ADCC capabilities and degranulation against a HLA-E+ target. Importantly, mAb-expanded adaptive NK cells did not upregulate PD-1 or other regulatory immune checkpoints that could dampen their function.

Conclusions

By this study we provide hints to improve previous expansion methods, by eliminating the use of genetically modified cells as stimulators, and obtaining effectors not expressing unwanted inhibitory receptors. This new protocol for expanding functional adaptive NK cells is safe, cost-effective and easily implementable in a GMP context, suitable for innovative immunotherapeutic purposes.
Identification and validation of diagnostic genes IFI44 and IRF9 in insomnia-associated autoimmune uveitis
Authors: Wu Chao , Feng Hui , Tian Meng , Chu Baorui , Liu Xianyang , Zeng Shuhao , Wang Yakun , Wang Hong , Hou Shengping , Liang Qingfeng
Published: January 2025

Objective

Insomnia is increasingly recognized as a significant factor in the development of various autoimmune diseases, including autoimmune uveitis (AU). We investigated insomnia-associated genes that may contribute to AU pathogenesis and sought to identify potential biomarkers for insomnia-associated AU.

Methods

Microarray data related to insomnia and AU were downloaded from the Gene Expression Omnibus (GEO) database and analyzed. The GEO2R tool was used to identify differentially expressed genes (DEGs) that were common between insomnia and AU. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI), functional enrichment, and CMap analyses were then performed to identify pathogenic genes, underlying mechanisms, and potential therapeutic drugs for insomnia-associated AU. Least absolute shrinkage and selection operator regression was employed to screen for candidate biomarkers, and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curves and quantitative polymerase chain reaction (qPCR). Finally, molecular docking was applied to verify binding activities.

Results

We identified 138 up-regulated and 85 down-regulated DEGs that were common to insomnia and AU. PPI network analysis highlighted 10 key genes, CMap analysis identified 30 compounds, and WGCNA revealed 54 key genes and 30 compounds. Intersection of the above-mentioned key genes and compounds identified six genes and five compounds. After verification by qPCR and ROC curve analysis, IFI44 and IRF9 were confirmed as hub genes. Finally, two compounds were selected based on docking scores of less than −7 kcal/mol.

Conclusion

Our study demonstrated involvement of the viral response in both insomnia and AU and identified the diagnostic significance of IFI44 and IRF9 in these conditions. These findings provide novel insights for future diagnostic and therapeutic strategies to treat insomnia-associated AU.
Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients. A systematic review and meta-analysis
Authors: Lallas Konstantinos , Chatziioannou Eftychia , Durak Derya , Frey Georg , Serna-Higuita Lina Maria , Rasch Marie-Lena , Kyrgidis Athanassios , Timotheadou Eleni , Apalla Zoe , Leiter Ulrike , Flatz Lukas , Lallas Aimilios , Amaral Teresa
Published: January 2025

Background

Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce.

Objective

To systematically review the evidence concerning the impact of treatment discontinuation with ICIs for reasons other than progressive disease (PD) on relapse rates and survival of melanoma patients.

Methods

A systematic literature search was conducted in three electronic databases until July 2024. Studies referring to melanoma patients who ceased ICIs electively (i.e. due to complete response (CR), protocol completion or patient/physician’s wish) or due to treatment-limiting toxicities (TLTs) were selected. Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity.

Results

38 and 35 studies were included in qualitative and quantitative synthesis, respectively. From 2542 patients discontinued treatment with ICIs electively or due to TLTs, 495 experienced progression [number of studies (n)=34, RR 20.9%, 95%CI 17.1 – 24.7%, I2 85%) and higher rates were detected in patients with TLTs compared to elective discontinuation. Mean time to PD was 14.26 months (n=18, mean time 14.26, 95%CI 11.54 – 16.98, I2 93%) and was numerically higher in patients who ceased for CR compared to patients with TLTs. Treatment duration before cessation was not associated with risk and time to relapse, while mucosal melanomas and non-CR as BOR during treatment led to increased risk for relapse and shorter time to PD compared to other histologic subtypes or CR. Rechallenge with ICI resulted in 57.3% DCR and 28.6% pooled CR rates (n=22, CR rate 28.6%, 95%CI 17.1 – 40.2, I2 68%). Heterogeneity among studies was high, but subgroup analysis based on type of ICI used (anti-CTL4 and anti-PD1 inhibitor or anti-PD1 monotherapy) and type of study (RCTs or observational studies), along with sensitivity analyses did not reveal significant alterations in results.

Conclusion

Discontinuation of ICIs in patients without progression is possible. Outcomes to rechallenge with ICIs may differ depending on the reason for discontinuation, but remains a considerable option.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024547792.
The role of complement in tumor immune tolerance and drug resistance: a double-edged sword
Authors: Yang Ronghui , Fu Di , Liao Aijun
Published: January 2025

The domain of cancer treatment has persistently been confronted with significant challenges, including those associated with recurrence and drug resistance. The complement system, which serves as the foundation of the innate immune system, exhibits intricate and nuanced dual characteristics in the evolution of tumors. On the one hand, the complement system has the capacity to directly inhibit cancer cell proliferation via specific pathways, thereby exerting a beneficial anti-tumor effect. Conversely, the complement system can also facilitate the establishment of an immune escape barrier for cancer cells through non-complement-mediated mechanisms, thereby protecting them from eradication. Concurrently, the complement system can also be implicated in the emergence of drug resistance through a multitude of complex mechanisms, directly or indirectly reducing the efficacy of therapeutic interventions and facilitating the progression of cancer. This paper analyses the role of the complement system in tumors and reviews recent research advances in the mechanisms of tumor immune tolerance and drug resistance.
Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV
Authors: Helble Michaela , Zhu Xizhou , Bhojnagarwala Pratik S. , Liaw Kevin , Gao Yangcheng , Kim Amber , Bayruns Kelly , McCanna Madison E. , Park Joyce , Konrath Kylie M. , Garfinkle Sam , Brysgel Taylor , Weiner David B. , Kulp Daniel W.
Published: January 2025

Oncogenic forms of HPV account for 4.5% of the global cancer burden worldwide. This includes cervical, vaginal, vulvar, penile, and anal cancers, as well as head and neck cancers. As such, there is an urgent need to develop effective therapeutic vaccines to drive the immune system’s cellular response against cancer cells. One of the primary goals of cancer vaccination is to increase the potency and diversity of anti-tumor T-cell responses; one strategy to do so involves the delivery of full-length cancer antigens scaffolded onto DNA-launched nanoparticles to improve T-cell priming. We developed a platform, making use of structural prediction algorithms such as AlphaFold2, to design stabilized, more full-length antigens of relevant HPV proteins and then display them on nanoparticles. We demonstrated that many such designs for both the HPV16 E6 and E7 antigens assembled and drove strong CD8+ T-cell responses in mice. We further tested nanoparticles in a genetically diverse, more translationally relevant CD-1 mouse model and demonstrated that both E6 and E7 nanoparticle designs drove a CD8+ biased T-cell response. These findings serve as a proof-of-concept study for nanoparticle antigen design as well as identify new vaccine candidates for HPV-associated cancers.
The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors
Authors: Zhou Jiajun , An Wenhao , Guan Lei , Shi Jinyu , Qin Qiaozhen , Zhong Shuai , Huang Zheng , Liu Rui , Wu Chenxing , Ma Zhong , Qi Xueling , Jiang Xiaoxia , Wang Yan , Li Shouwei
Published: January 2025

Background

Primary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance remain poorly understood.

Methods

This study included 93 paraffin-embedded tissue samples from 90 patients diagnosed with CNS GCTs. Immunohistochemistry and immunofluorescence staining were used to assess the infiltration patterns of T cell subsets (CD3+, CD4+, CD8+, Foxp3+) and the expression levels of immune checkpoints (CTLA-4, PD-1, PD-L1). Additionally, the study explored the relationship between these immune features and the patient’s clinical characteristics and prognosis.

Results

The study revealed that germinomas exhibited significantly higher infiltration of CD4+ and Foxp3+ T cells compared to non-germinomatous GCTs (NGGCTs). Additionally, CTLA-4 expression was detected in 58.06% of cases, while PD-1 and PD-L1 were expressed in over 90%, with higher CTLA-4 levels in germinomas and elevated PD-L1 levels in NGGCTs. T cell infiltration was positively correlated with immune checkpoint expression, particularly in germinomas. The results also highlighted the strong immunosuppressive nature of the CNS GCTs’ tumor microenvironment. Furthermore, T cell infiltration and immune checkpoint expression were closely associated with clinical characteristics and prognosis. Notably, PD-1 expression was identified as an independent prognostic factor for progression-free survival (PFS) and recurrence-free survival (RFS).

Conclusion

Our study highlighted the distinct characteristics of T cell infiltration and the significant expression of immune checkpoints in CNS GCTs, revealing the highly heterogeneous and immunosuppressive nature of the tumor microenvironment. PD-1 expression was identified as an independent prognostic predictor, offering a foundation for enhancing risk stratification in CNS GCT patients. These findings also support the potential for future clinical applications of immune checkpoint inhibitors, such as PD-1 monoclonal antibodies.
High rate of false positive malaria rapid diagnostic tests in a district hospital in Uganda
Authors: Mortazavi Susanne E. , Lugaajju Allan , Ivarsson Anna-Clara , Karlsson Söbirk Sara , Norrgren Hans , Persson Kristina E. M.
Published: January 2025

Background

Malaria remains a significant health burden, particularly in Uganda, which has one of the highest incidence rates globally. Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis due to their ease of use and affordability in resource-limited settings. However, false-positive RDT results may lead to unnecessary antimalarial treatments and missed diagnoses of other febrile conditions. This study aimed to evaluate the diagnostic accuracy of RDT compared to microscopy and loop-mediated isothermal amplification (LAMP) in a malaria-endemic region of Uganda.

Methods

A prospective study was conducted with 225 febrile individuals diagnosed with malaria using RightSign Malaria Ag HRPII/Pan Plasmodium Aldolase RDT (Hangzhou Biotest Biotech Co., Ltd., China) at Iganga General Hospital, Uganda. Blood samples were analyzed using microscopy and LAMP. Demographic information, malaria history, and parasitemia levels were also recorded.

Results

Among the RDT-positive participants, 48% tested negative by microscopy, and 45% of these were also negative by LAMP, indicating that 20% of all RDT-positive individuals were likely false positives. Overall, 66% (149/225) of RDT-positive cases were confirmed as true positives.

Conclusions

This study identified a high rate of false positives with the tested RDT, risking inappropriate treatment and missed diagnoses of other illnesses. It is essential that healthcare facilities use RDTs validated and recommended by the World Health Organization (WHO) to ensure high specificity and accuracy, particularly in resource-limited settings where alternative diagnostic methods may not be available.
Re-analysis of the current status of clinical trial registration in China
Authors: Li Shuwen , Li Jianhao , Zeng Wenjing , Li Zhicheng , Zhang Jietong , Wang Siying , Xu Nenggui , Li Zeli
Published: January 2025

Objective

To reanalyze and summarize the current status and deficiencies of clinical trial registration in China, based on an analysis of the situation of clinical trial registration in the Chinese Clinical Trial Registry (ChiCTR).

Methods

A search was conducted in China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wangfang Data, VIP Database for Chinese Technical Periodicals (VIP), Web of Science (WoS), PubMed up to December 31, 2023, for literature on the analysis of clinical trial registration based on ChiCTR. NoteExpress software was used for screening, EXCEL for data organization and analysis, the Word Cloud website for constructing word frequency maps, and Origin software for visualization.

Results

Among the 94 articles included, common analysis items included the number of registered projects, types of research, registration time, types of registration institutions, and regional distribution. Most of the included literature was funded. The publishing institutions involved 20 provinces/municipalities across the country, with hospitals being the majority of the publishing units. Most literature was submitted shortly after search completion and published shortly after submission, with more than half of the articles published in high-quality journals. The total average citation count of the literature was 3.34. The sources of clinical trial registration platforms analyzed in the literature were divided into three categories: single platform, dual platform, and multiple platforms.

Conclusion

ChiCTR plays a key role in enhancing transparency in clinical research, promoting standardization and normalization of research, strengthening domestic and international scientific research cooperation, and advancing medical innovation and public health improvement. However, there are still issues with the quality of registration, focus areas, and the evaluation of registration quality.
Local sympathetic nerve depletion does not alter vitiligo progression in a mouse model
Authors: Hu Zhichao , Chen Ting , Chen Daoming
Published: January 2025

Vitiligo, an autoimmune skin disorder characterized by melanocyte loss, has long been associated with sympathetic nervous system activity. Clinical observations have suggested links between psychological stress, sympathetic activation, and vitiligo progression. However, direct experimental evidence for the role of sympathetic nerves in vitiligo development has been lacking. Herein, we employed 6-hydroxydopamine (6-OHDA) to induce sympathetic nerve depletion in mice before vitiligo induction. Sympathetic nerve ablation was confirmed through immunofluorescent staining of tyrosine hydroxylase. Vitiligo progression was assessed by quantifying epidermal melanocytes and CD8+ T cells using whole-mount immunofluorescence staining. The loss of melanocytes and infiltration of CD8+ T cells in vitiligo lesions were comparable between sympathectomized and control mice. Overall, our study suggested that previously observed associations between sympathetic nervous system activity and vitiligo may be concomitant effects rather than causative factors, challenging long-held clinical hypotheses.
The diagnosis of DIC: a current overview
Authors: Yang Hongyu , Ma Xiaochun , Li Xu
Published: January 2025

The name of disseminated intravascular coagulation (DIC) and its diagnostic criteria remain controversial. DIC is a clinical syndrome caused by a variety of etiologies, which determines its high heterogeneity. It is inappropriate to adopt the same diagnostic criteria. DIC has its common characteristics. First, in most DIC, thrombosis and bleeding coexist. Second, DIC is a dynamic process. Third, endothelial cell injury and systemic coagulation activation are the core of DIC. Fourth, DIC is an initiating factor of multiple organ dysfunction syndrome (MODS). There are still controversies about the diagnostic criteria of DIC. First, it relies on clinical manifestations and laboratory tests, which cannot reflect pathophysiology. Second, the clinical manifestations were not sensitive or specific. Third, there is a lack of sensitive biomarkers. Fourth, the parameters in the current diagnostic criteria cannot fully reflect the actual coagulation function. Fifth, it is obviously inappropriate to use the same scoring system for diagnosis of clinical syndromes with different etiologies and pathophysiology. Therefore, it is urgent to re-establish the diagnostic criteria for DIC. In recent years, the understanding of DIC has been continuously improved, including the in-depth understanding of the pathogenesis, the classification of coagulation phenotypes, and the development of the “two-step” diagnosis of DIC, etc. All of these contribute to the establishment of new diagnostic criteria for DIC. In conclusion, it is necessary to develop personalized diagnostic criteria based on etiology, reflecting pathophysiological mechanisms, establishing clear cut-off values for parameters, being clinical applicable, being globally unified, and most importantly, being able to identify therapeutic targets.
Comparison of macular retinal thickness measurements using spectral-domain and swept-source optical coherence tomography in healthy eyes
Authors: Wan Huan , Wu Zhaode , Liu Ziling , Qin Bo
Published: January 2025

Aim

This study compares retinal thickness measurements in healthy eyes using one SD-OCT and two SS-OCT devices to assess differences and consistency for clinical application.

Methods

Forty-eight eyes with a mean age of 28.15 ± 8.85 years were enrolled. Retinal thickness was measured using Heidelberg Spectralis SD-OCT, Svision VG200 SS-OCT, and TowardPi En Face SS-OCT. Normally distributed data were presented as mean ± SD; non-normal data as median (P25–P75). Intraclass correlation coefficients (ICC) and Bland–Altman analysis were used to assess agreement, with a 7 μm error threshold.

Results

Significant differences were found between the three devices (p < 0.001). SD-OCT measurements were consistently lower than SS-OCT (p < 0.001), while the two SS-OCT devices showed no significant differences except in the nasal region (p = 0.006). ICC values between SD-OCT and SS-OCT devices were low (0.125–0.532), while SS-OCT devices showed better agreement (ICC: 0.369–0.922). Bland–Altman analysis found only 8.33% of SD-OCT and SS-OCT measurements within the 7 μm error range, compared to 81.25–83.33% for SS-OCT devices.

Conclusion

The measurements of macular retinal thickness using SD-OCT and SS-OCT devices showed poor consistency and cannot be used interchangeably. However, measurements obtained from different SS-OCT devices demonstrated good consistency. To enhance the accuracy of results, it is recommended to maintain consistency in the devices used for follow-up examinations in the same patient.
Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases
Authors: Chen Shuai , Shen Caifei , Zeng Xiaorui , Sun Luqiang , Luo Fangli , Wan Renhong , Zhang Yupeng , Chen Xinyun , Hou Yujun , Wang Wen , Zheng Qianhua , Li Ying
Published: January 2025

The interplay between energy metabolism and the gut barrier is crucial for maintaining intestinal physiological homeostasis. Energy metabolism and the intestinal barrier perform distinct yet complementary roles that uphold intestinal ecological equilibrium. Disruptions in energy metabolism can compromise the integrity of the intestinal barrier; for example, inactivation of the AMPK pathway may lead to reduced expression of proteins associated with tight junctions. Conversely, impairment of the intestinal barrier can result in metabolic dysregulation, such as alterations in the gut microbiota that impede the production of short-chain fatty acids (SCFAs), which are essential substrates for energy metabolism. This disruption can affect energy production and modify the gut’s hypoxic environment. Imbalances in these systems have been associated with the onset of various intestinal diseases. Research indicates that dietary interventions, such as a low FODMAP diet, can enhance the colonization of probiotics and improve the fermentation metabolism of SCFAs. Pharmacological strategies to elevate SCFA levels can activate the AMPK pathway and rectify abnormalities in energy metabolism. This review provides a comprehensive summary of recent advancements in elucidating the interactions between energy metabolism and the intestinal barrier.
Portable solutions for plant pathogen diagnostics: development, usage, and future potential
Authors: Yadav Anurag , Yadav Kusum
Published: January 2025

The increasing prevalence of plant pathogens presents a critical challenge to global food security and agricultural sustainability. While accurate, traditional diagnostic methods are often time-consuming, resource-intensive, and unsuitable for real-time field applications. The emergence of portable diagnostic tools represents a paradigm shift in plant disease management, offering rapid, on-site detection of pathogens with high accuracy and minimal technical expertise. This review explores portable diagnostic technologies’ development, deployment, and future potential, including handheld analyzers, smartphone-integrated systems, microfluidics, and lab-on-a-chip platforms. We examine the core technologies underlying these devices, such as biosensors, nucleic acid amplification techniques, and immunoassays, highlighting their applicability to detect bacterial, viral, and fungal pathogens in diverse agricultural settings. Furthermore, the integration of these devices with digital technologies, including the Internet of Things (IoT), artificial intelligence (AI), and machine learning (ML), is transforming disease surveillance and management. While portable diagnostics have clear advantages in speed, cost-effectiveness, and user accessibility, challenges related to sensitivity, durability, and regulatory standards remain. Innovations in nanotechnology, multiplex detection platforms, and personalized agriculture promise to further enhance the efficacy of portable diagnostics. By providing a comprehensive overview of current technologies and exploring future directions, this review underscores the critical role of portable diagnostics in advancing precision agriculture and mitigating the impact of plant pathogens on global food production.
The role of mycobacteremia screening in enhancing non-tuberculous mycobacteria detection in hospitalized persons with HIV
Authors: Miao Mengjiao , Zhu Hongyan , Liu Ziyao , Yang Jinjin , Zhang Yiting , Ma Chenyu , Qin Jiamin , Chen Yaling , Wei Hongxia , Chen Wei , Yang Yongfeng , Hu Zhiliang
Published: January 2025

Among hospitalized severely immunocompromised persons with HIV (PWH), non-tuberculous mycobacteria (NTM) may be under-diagnosed due to non-specific symptoms undifferentiable with other opportunistic infections. To evaluate the prevalence of NTM mycobacteremia and how screening for mycobacteremia assistant with identification of NTM infections, this study retrospectively analyzed 1,136 hospitalized PWH with CD4 counts <200 cells/μL, who underwent mycobacteremia screening at a tertiary hospital in Nanjing, China, between July 2018 and December 2023. The prevalence of non-tuberculous mycobacteremia was 5.8% (95% CI, 4.6–7.3%), with a higher prevalence of 8.6% (95% CI, 6.7–10.9%) in patients with CD4 counts <50 cells/μL, compared to 1.4% (95% CI, 0.6–3.0%) in those with CD4 counts ≥50 cells/μL. Mycobacterium avium complex (MAC) was the predominant pathogen, representing 95% (95% CI, 86.7–98.3%) of positive blood cultures, though it accounted for only 66.2% (95% CI, 54.3–76.3%) of NTM species isolated from respiratory samples. The sensitivity of mycobacterial blood cultures (MBC) in diagnosing all culture-proven NTM infections was 63.9% (95% CI, 54.0–72.8%), increasing to 75.7% (95% CI, 64.8–84.0%) in patients with CD4 counts <50 cells/μL. Notably, mycobacteremia served as the sole microbiological evidence in approximately 25% of all culture-proven NTM infections during initial hospitalization, where other specimen sources failed to yield conclusive evidence. These findings underscore the importance of mycobacteremia screening in improving the detection of NTM infections among severely immunocompromised hospitalized patients, especially those with CD4 counts <50 cells/μL, and highlight the value of incorporating MBC into diagnostic protocols to enhance clinical management of these high-risk individuals.
Occurrence of antibiotics and antibiotic resistance genes at various stages of different aquaculture modes surrounding Tai Lake, China
Authors: Wu Congcong , Ye Haitao , Xu Mingzhu , Zhao Xuan , Zhao Xuejie , Li Lina , Li Mingzhi , Wei Yanfei , Li Yuru , Hu Baolan
Published: January 2025

Introduction

Aquaculture is an important source of antibiotics and ARGs in environmental waters. However, the occurrence of antibiotics and ARGs under different modes and stages of aquaculture has rarely been systematically studied.

Methods

This paper uses qPCR, LC-MS, and High-Throughput sequencing across different culture modes and stages to investigate antibiotics, resistance genes, and microbial communities in the water bodies, and analyze contamination differences between these modes.

Results

The quinolone and chloramphenicol were the main antibiotics, and the highest absolute abundance genes were quinolone resistance genes (qnrB) and quinolone resistance genes (sul1), with the mobile genetic element (MGE) intI1, both of which exhibited a gradual seasonal increase. Microbial diversity also varies seasonally, especially with a gradual increase in the abundance of some pathogenic bacteria (Flavobacterium). Antibiotics and resistance genes were found at higher levels in fish ponds compared to shrimp and crab ponds, while they were lower in shrimp and crab ponds that utilized the ecological mode ponds than in the traditional culture mode ponds.

Conclusion

Our study presents a comprehensive characterization of antibiotics and ARGs in aquaculture waters from various perspectives. Ecological aquaculture modes contribute to reducing antibiotic and resistance gene pollution in water bodies. These findings will support the optimization of aquaculture mode and antibiotic usage to the green and sustainable development of aquaculture finally.
Association of systemic inflammatory response index and stroke: a cross-sectional study of NHANES, 2005–2018
Authors: Tian Aokai , Zheng Yafang , Jin Jing , Huang Chunyuan
Published: January 2025

Background

Many inflammatory markers like systemic immune-inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) are associated with stroke. However, studies on the relationship between stroke and systemic inflammatory response index (SIRI) are scarce. This study was aimed at evaluating the potential association of SIRI with stroke.

Methods

Our cross-sectional study included adults with sufficient SIRI and stroke data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). We used multivariable logistic regression, interaction tests, smoothed curve fitting, and subgroup analysis for assessing the independent relationship between SIRI and stroke.

Results

Of 36,176 participants in this study, 1,414 (3.9%) had experienced a stroke. In a fully adjusted model, the systemic inflammatory response index displayed a significant and positive correlation with stroke (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.04–1.15, p = 0.0006). Meanwhile, the odds of stroke increased by 39% in the 4th quartile, relative to the 1st quartile (OR = 1.39, 95% CI = 1.17–1.65, p = 0.0002). Additional interaction tests and subgroup analysis revealed that age, sex, race, education, marriage, BMI (body mass index), smoking, diabetes mellitus, hypertension, and coronary heart disease (CHD) were not positively correlated (p interaction >0.05). Moreover, we also found a nonlinear correlation between SIRI and stroke, with an inflection point of 2.17.

Conclusion

Our results indicate that SIRI is significantly and positively related to stroke; however, its role in stroke needs to be further confirmed by large-scale prospective studies.
Association between folate and glutamine metabolism and prognosis of kidney cancer
Authors: Qin Jiaxuan , Ouyang Chaoyue , Zhuang Xuan
Published: January 2025

Background

Recent studies have shown that folate metabolism might influence cancer progression by regulating mitochondrial metabolism and glutamine is involved in the development and progression of several malignancies. This study aimed to explore the association between folate and glutamine metabolism and prognosis of kidney cancer.

Methods

We performed expression analysis, survival analysis, genetic alteration analysis, and tumor immune infiltrate analysis of related genes using platforms such as UALCAN, GEPIA, GEPIA2, cBioPortal, and TIMER. Serum folate, vitamin B12, and methylmalonic acid levels and clinical information of participants in the United States diagnosed with kidney cancer was obtained from the National Health and Nutrition Examination Survey (NHANES) and analyzed using software R.

Results

We observed that RNA expression levels of certain folate and glutamine metabolism-related genes, particularly MTHFD2 and SLC1A5, were associated with the prognosis of kidney renal clear cell carcinoma (KIRC). Expression differences in these genes were notable between high-stage and low-stage and N1 vs. N0 lymph node metastasis status in KIRC. There was a positive association between glutamine metabolism-related genes and folate metabolism-related genes in KIRC. SLC1A5 was positively correlated with MTHFD2 in KIRC. Folate and glutamine metabolism might play a synchronous role in KIRC prognosis. Strong correlations between MTHFD2 and SLC1A5 expression with KIRC immune infiltrates were found. Higher levels of serum folate may be related to improved cancer-specific survival (CSS) in kidney cancer patients in the U.S.

Conclusion

Folate and glutamine metabolism-related genes, especially SLC1A5 and MTHFD2, were associated with the prognosis, tumor stage, and lymph node metastasis status in KIRC. Higher KIRC SLC1A5 or MTHFD2 expression levels were associated with higher tumor stages, increased lymph node metastasis possibilities, poorer OS, and poorer RFS. Elevated levels of serum folate may be associated with improved CSS in kidney cancer patients in the United States.
Associations between ultra-processed foods intake and preserved ratio impaired spirometry in U.S. adults
Authors: Kong Weiliang
Published: January 2025

Background

Preserved Ratio Impaired Spirometry (PRISm) is increasingly recognized as a precursor to Chronic Obstructive Pulmonary Disease (COPD). The impact of Ultra-Processed Foods (UPFs) intake on PRISm and lung function remains underexplored, and we aimed to explore their associations.

Methods

This study included 8,336 U.S. adults. Weighted logistic and linear regression models were employed for main analysis. Dose–response relationship was examined through restricted cubic spline (RCS) analysis, and subgroup analyses explored interactions with selected covariates.

Results

Participants in the PRISm group were older and exhibited various adverse health characteristics. The percentage of total daily energy intake from UPFs (%Kcal) intake was associated with a non-significant increase in PRISm risk (OR 1.67, 95% CI: 0.96–2.92, p = 0.07). However, the highest quartile of UPFs (%Kcal) intake was significantly linked to increased PRISm risk (OR 1.36, 95% CI: 0.99–1.86, P for trend = 0.043). Furthermore, higher UPFs (%Kcal) intake negatively affected lung function, with participants in the highest quartile showing a significant reduction in forced expiratory volume in 1 s (FEV1) of −45.5 mL (95% CI: −87.6 to −3.4, P for trend = 0.045) and a decrease in forced vital capacity (FVC) of −139.4 mL (95% CI: −223.5 to −55.4, p < 0.001) compared to those in the lowest quartile. RCS analysis demonstrated linear relationships for both PRISm and lung function. Subgroup analysis revealed increased susceptibility primarily among individuals with occupational exposure. Additionally, sensitivity analysis indicated that a higher percentage of total daily intake from UPFs (%Grams) intake was significantly associated with an increased risk of PRISm (OR 1.86, 95% CI: 1.07–3.25, p = 0.03).

Conclusion

Higher intake of UPFs is linked to an increased risk of PRISm and negatively affects lung function, particularly in individuals with occupational exposure.
The prognostic significance of malnutrition in older adult patients with acute ischemic stroke
Authors: Jiang Tian-Tian , Zhu Xing-Yu , Yin Yan-Wei , Liu Hong-Jin , Zhang Guang-Yun
Published: January 2025

Background

Malnutrition is associated with an unfavorable prognosis; however, malnutrition in hospitalized patients is frequently overlooked by clinicians. This highlights the importance of accurately assessing nutritional status and providing appropriate nutritional supplementation. The most appropriate nutritional assessment tool for predicting the short-term prognosis of older adult patients with Acute Ischemic Stroke (AIS) was identified from five nutritional assessment tools, including the Prognostic Nutrition Index (PNI), the Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score, the Naples Prognostic Score (NPS), the Geriatric Nutritional Risk Index (GNRI), and the Controlling Nutritional Status (CONUT) Score.

Methods

A total of 585 older adult patients with Acute Ischemic Stroke (AIS) were retrospectively analyzed and divided into two groups according to the modified Rankin Scale (mRS) score. The first group, comprising 111 cases, was classified as having a poor prognosis (mRS score > 2), while the second group, consisting of 391 cases, was classified as having a good prognosis (mRS score ≤ 2). A total of five nutritional assessment tools, including PNI, HALP Score, NPS, GNRI, and CONUT, were employed to evaluate the nutritional status of older adult patients with AIS and for the analysis of the relationship between nutritional status and prognosis. The incremental value of five nutritional assessment tools in predicting patient prognosis was compared by means of the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). The efficacy of each nutritional assessment tool in forecasting the incidence of unfavorable outcomes in older adult patients with AIS within a one-year timeframe was evaluated by utilizing the area under the receiver operating characteristic curve (AUC), calibration curves, and decision analysis curves. Comparative analyses were also conducted.

Result

Among the five nutritional assessment tools, the PNI (AUC: 0.619, 95% CI: 0.560–0.679, p < 0.001) and HALP score (AUC: 0.612, 95% CI: 0.552–0.672, p < 0.001) demonstrated a significantly greater area under the ROC curve (AUC) compared to the NPS (AUC: 0.597, 95% CI: 0.536–0.658, p = 0.002), CONUT score (AUC: 0.582, 95% CI: 0.520–0.644, p = 0.009), and GNRI (AUC: 0.590, 95% CI: 0.529–0.651, p < 0.001). When compared to BMI, PNI exhibited a more pronounced improvement in the integrated discrimination index (IDI: 0.0203, p = 0.0061). Similarly, the net reclassification index (NRI) also showed a significant improvement (NRI: 0.2422, p = 0.024), indicating the superior performance of PNI in risk stratification.

Conclusion

Among the five types of nutritional assessment tools employed in this study, the PNI was the most effective at predicting a poor prognosis at one year in older adult patients with AIS.
Oncocytic papillary renal cell carcinoma (OPRCC): 2 case report and literature review
Authors: Wang Yanchen , Guan Lihui , Liu Yaming , Liu Yuxuan , Guo Xiaoyan , Sun Yaofei
Published: January 2025

Oncocytic papillary renal cell carcinoma (OPRCC) is a new papillary renal cell carcinoma (OPRCC) added to the 2016 WHO Classification of Tumors of the Urinary and Male Reproductive System. It is a subtype of carcinoma, PRCC, which is very rare and it is very characteristic and interesting. The morphology, immunophenotype, genetic characteristics and prognosis of OPRCC are uncertain, so the diagnosis and post-operative management of OPRCC are challenging. Recently, two patients with OPRCC have been treated in our hospital, both of whom have undergone surgical treatment. The information of these two cases is described as follows, and the literature is further reviewed to share the current diagnosis and treatment characteristics of OPRCC and the research progress after surgery. At the same time, the diagnosis of OPRCC disease is subdivided from PRCC disease, and the diagnosis of OPRCC disease is more precise. To optimize the individualized management of patients with renal cell carcinoma in order to improve the understanding and diagnosis of the disease.
A nomogram for predicting prognosis for young cervical neuroendocrine carcinoma: A SEER-based study and external validation
Authors: Xie Ning , Yu Haijuan , Lin Jie , Deng Sufang , Liu Linying , Sun Yang
Published: January 2025

Background

Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive subtype of cervical carcinomas with poor prognosis. NECC tends to occur in young age which could severely impair mental and physical health of young patients. Therefore, this study aims to develop an individualized prognostic nomogram for young NECC patients.

Methods

360 young (≤45 years old) NECC patients were retrospectively selected from the Surveillance, Epidemiology and End Results (SEER) database and were randomly located to a training cohort and an internal validation cohort in a ratio of 7:3. Data from Fujian Cancer Hospital was used as an external validation cohort. Independent prognostic factors were identified by univariate and multivariate Cox regression analysis, and a prognostic nomogram for young NECC was developed. The predictive accuracy and clinical utility of the nomogram were assessed by area under the time-dependent receiver operating characteristic (timeROC) curve (AUC), the concordance index (C-index), calibration plots, and decision curve analysis (DCA). Finally, a simplified scoring system for clinical use was constructed by dividing patients into high-risk and low-risk groups.

Results

Pathological type, FIGO stage, and surgery were independent risk factors by univariate and multivariate analysis (P < 0.05). The prognostic nomogram consisting of the above three independent risk factors had high accuracy. The AUC values of 5-year overall survival (OS) in the training, internal validation, and external validation cohorts were 0.805, 0.798 and 0.872, respectively. The prognostic nomogram also presented with good C-index and calibration plots. The DCA curve further confirmed that the nomogram had a high clinical net benefit. According to the median prognostic index (median PI=18.6), all patients were categorized into high-risk group and low-risk group. The 5-year OS of the high-risk NECC group was significantly worse than that of the low-risk group among three cohorts (P<0.05).

Conclusions

Pathological type, FIGO stage, and surgery were identified as independent prognostic risk factors for young NECC patients. Based on the nomogram, gynecologic oncologists can accurately and easily predict the prognosis of young NECC and provide scientific guidance for individualized treatment.
Antiangiogenic therapy with recombinant human endostatin may improve blood perfusion of cervical node with necrosis in nasopharyngeal carcinoma patients: a preliminary study by using contrast-enhanced ultrasound
Authors: Yang Zhendong , Xiao Huimin , Li Xigui , Wei Zhuxin , Kang Min , Wang Rensheng , Huang Jianyuan
Published: January 2025

Background

The cervical node with necrosis (CNN) is an important poor prognostic factor for nasopharyngeal carcinoma (NPC) patients. The tumor microenvironment of the CNN has severely insufficient blood perfusion, thus leading to hypoxia and reducing the effect of radiotherapy (RT) and chemotherapy. By using contrast-enhanced ultrasound (CEUS) as a monitoring method, we conducted this study to assess whether antiangiogenic therapy (AT) with recombinant human endostatin (RHES) may improve blood perfusion of the CNN.

Materials and methods

Fifteen NPC patients with CNN were enrolled and underwent CEUS the day before and day 5 after AT with RHES initiation, respectively. By analyzing the variations of CEUS parameters of CNN, such as peak intensity (PI), time to peak (TTP), and mean transit time (MTT) at different time points, we evaluate the impact of AT with RHES on blood perfusion of CNN.

Results

The PI of day 5 after AT was significantly enhanced compared to the PI of the day before AT [−44.94 ± 4.72 (dB) vs. −50.33 ± 6.85 (dB), p < 0.001]. The TTP of day 5 after AT became dramatically shorter than the TTP of the day before AT [19.48 ± 3.63 (s) vs. 24.19 ± 6.93 (s), p = 0.031]. The MTT of day 5 after AT became obviously shorter than the MTT of the day before AT [28.08 ± 3.03 (s) vs. 33.76 ± 6.20 (s), p = 0.001].

Conclusion

These results revealed that the blood volume and the blood flow velocity in the microvessels of the CNN increased after AT, indicating that AT with RHES may improve blood perfusion in the CNN of NPC, thus providing valuable insights for the clinical application of AT combined with RT and/or chemotherapy in NPC patients with CNN. Moreover, CEUS as a noninvasive and real-time monitoring method may be suitable for clinically evaluating tumor blood perfusion changes.