bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the efficacy and safety of perioperative immunochemotherapeutic strategies for locally advanced esophageal cancer: a systematic review and network meta-analysis
Authors: Zhang Jiao , Zhao Peixi , Xu Rui , Han Le , Chen Wenjuan , Zhang Yili
Published: December 2024

Background

The aim of this network meta-analysis was to clarify the efficacy and safety of different immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the neoadjuvant phase for the treatment of locally advanced esophageal cancer.

Methods

We searched PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang databases from January 2000 until May 2024. The primary endpoints were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), treatment-related adverse events(TRAEs) of any grade and TRAEs of grade 3 or higher. The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias tool were used to evaluate risk of bias. To analyze the data, Review Manager 5.3 and Stata16.0 were applied.

Results

Fourteen eligible studies (six randomized controlled trials) and 8 retrospective cohort studies) enrolling 1139 patients were included for this network meta-analysis. All studies originated from China. For patients with locally advanced esophageal cancer, neoadjuvant immunochemotherapeutic strategies showed significant advantages over traditional neoadjuvant therapy in terms of pCR, MPR, ORR and DCR. Among the analyzed regimens, camrelizumab plus chemotherapy demonstrated the most pronounced improvements in pCR and MPR, while pembrolizumab plus chemotherapy achieved the best outcomes in terms of ORR and DCR. There were no significant differences observed among the various neoadjuvant treatment strategies regarding R0 resection rate, any grade TRAEs, or grade≥3 TRAEs. The most common TRAEs in the neoadjuvant chemotherapy plus immunotherapy group were myelosuppression and gastrointestinal damage, with most grade 3 or higher TRAEs being hematologic adverse events. The most frequent immune-related adverse events(irAEs) included rash (4.2-21.7%), thyroid dysfunction (hypothyroidism or hyperthyroidism, 6.3-17.4%), and pneumonia (4.2-6.3%), with the majority being mild to moderate (grade 1 or 2).

Conclusions

Neoadjuvant immunotherapy combined with chemotherapy regimens demonstrate relatively high efficacy and tolerable safety profiles. Among the evaluated regimens, the combination chemotherapy with camrelizumab had relatively high pCR and MPR, whereas the combination chemotherapy with pembrolizumab had relatively high ORR and DCR. There were no significant differences in safety among the various regimens. Our study suggests that evaluating the efficacy and safety of different ICIs may be helpful in clinical decision-making.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024583548.
Tumor-infiltrating lymphocytes in melanoma: from prognostic assessment to therapeutic applications
Authors: Bida Meshack , Miya Thabiso Victor , Hull Rodney , Dlamini Zodwa
Published: December 2024

Malignant melanoma, the most aggressive form of skin cancer, is characterized by unpredictable growth patterns, and its mortality rate has remained alarmingly high over recent decades, despite various treatment approaches. One promising strategy for improving outcomes in melanoma patients lies in the early use of biomarkers to predict prognosis. Biomarkers offer a way to gauge patient outlook early in the disease course, facilitating timely, targeted intervention. In recent years, considerable attention has been given to the immune response’s role in melanoma, given the tumor’s high immunogenicity and potential responsiveness to immunologic treatments. Researchers are focusing on identifying predictive biomarkers by examining both cancer cell biology and immune interactions within the tumor microenvironment (TME). This approach has shed light on tumor-infiltrating lymphocytes (TILs), a type of immune cell found within the tumor. TILs have emerged as a promising area of study for their potential to serve as both a prognostic indicator and therapeutic target in melanoma. The presence of TILs in melanoma tissue can often signal a positive immune response to the cancer, with numerous studies suggesting that TILs may improve patient prognosis. This review delves into the prognostic value of TILs in melanoma, assessing how these immune cells influence patient outcomes. It explores the mechanisms through which TILs interact with melanoma cells and the potential clinical applications of leveraging TILs in treatment strategies. While TILs present a hopeful avenue for prognostication and treatment, there are still challenges. These include understanding the full extent of TIL dynamics within the TME and overcoming limitations in TIL-based therapies. Advancements in TIL characterization methods are also critical to refining TIL-based approaches. By addressing these hurdles, TIL-focused research may pave the way for improved diagnostic and therapeutic options, ultimately offering better outcomes for melanoma patients.
Efficacy and safety of adding immune checkpoint inhibitors to first-line standard therapy for recurrent or advanced cervical cancer: a meta-analysis of phase 3 clinical trials
Authors: Zhang Xinmiao , Shen Jinhai , Huang Mengfan , Li Rongxia
Published: December 2024

Background

Immune checkpoint inhibitors (ICIs) combined with standard therapy (ST) have emerged as a novel treatment strategy for recurrent or advanced cervical cancer (r/a CC). However, the available data from phase 3 clinical trials have yielded mixed results. This study aims to evaluate the therapeutic efficacy and safety of adding ICIs to ST in the treatment of r/a CC.

Methods

Data from four phase 3 clinical trials (KEYNOTE-826, CALLA, BEATcc, and ENGOT-cx11/GOG-3047/KEYNOTE-A18), involving 2,857 patients, were analyzed. Meta-analyses were conducted to combine hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) for the objective response rate (ORR), and relative risks (RRs) for adverse events (AEs).

Results

The addition of ICIs to ST significantly improved PFS (HR, 0.67; 95% CI, 0.60-0.75), OS (HR, 0.66; 95% CI, 0.58-0.75), and ORR (OR, 1.48; 95% CI, 1.13-1.94) compared to ST alone. However, there was a modest increase in grade 3-5 AEs (RR, 1.08; 95% CI, 1.03-1.13) with the combined therapy.

Conclusion

This meta-analysis indicates that the combination of ICIs with ST in the treatment of r/a CC not only demonstrates superior efficacy over ST alone but also maintains a comparable toxicity profile, offering strong evidence for an effective and relatively safe treatment approach for managing this disease.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024593895.
Extra X, extra questions: Trisomy X syndrome and IgA deficiency – a case report
Authors: Leone Fabrizio , Gori Alessandra , Cinicola Bianca Laura , Brindisi Giulia , Maglione Vittorio , Anania Caterina , Zicari Anna Maria
Published: December 2024

While Trisomy X syndrome is typically characterized by developmental and cognitive variations, it is not commonly associated with immunodeficiencies. We report the unique case of a 6-year-old girl with Trisomy X presenting with selective IgA deficiency, challenging the conventional understanding of this chromosomal condition. The patient exhibited recurrent respiratory infections and gastrointestinal symptoms, evaluated in the context of her genetic background of Trisomy X and significantly low levels of IgA (0.03 g/L), yet normal IgG and IgM levels. Immunological assessment revealed a poor response to vaccination to HBV, necessitating an adapted vaccination strategy. Gastrointestinal investigations indicated paradoxical diarrhea secondary to chronic constipation, managed with dietary interventions. The presence of an extra X chromosome raises questions about the potential over-expression of genes that escape X-chromosome inactivation, such as FOXP3, which is crucial for the regulation of regulatory T cells. An abnormal expression of FOXP3 could lead to either heightened immune regulation, increasing susceptibility to infections, or to immune dysregulation. Although Trisomy X is not typically associated with immunodeficiencies, this case, paralleled by another patient with Trisomy X and CVID, suggests a need for further speculative research into possible genetic links. Moreover, a 1969 study reported lower IgA levels in women with an extra X chromosome. In conclusion, this case aims to underscore the necessity for a deeper genetic and immunological evaluation in chromosomal anomalies like Trisomy X to fully understand their speculative impact on immune function.
Unravelling turbot (Scophthalmus maximus) resistance to Aeromonas salmonicida: transcriptomic insights from two full-sibling families with divergent susceptibility
Authors: Pereiro Patricia , Tur Ricardo , García Miguel , Figueras Antonio , Novoa Beatriz
Published: December 2024

Introduction

Furunculosis, caused by the gram-negative bacterium Aeromonas salmonicida subsp. salmonicida, remains a significant threat to turbot (Scophthalmus maximus) aquaculture. Identifying genetic backgrounds with enhanced disease resistance is critical for improving aquaculture health management, reducing antibiotic dependency, and mitigating economic losses.

Methods

In this study, five full-sibling turbot families were challenged with A. salmonicida, which revealed one family with significantly greater resistance. Transcriptomic analyses (RNA-Seq) were performed on resistant and susceptible families, examining both naïve and 24-h postinfection (hpi) samples from head kidney and liver tissues.

Results

In the absence of infection, differentially expressed genes (DEGs) were identified predominantly in the liver. Following infection, a marked increase in DEGs was observed in the head kidney, with many genes linked to immune functions. Interestingly, the resistant family displayed a more controlled inflammatory response and upregulation of genes related to antigen presentation and T-cell activity in the head kidney at early infection stages, which may have contributed to its increased survival rate. In the liver, transcriptomic differences between the families were associated mainly with cytoskeletal organization, cell cycle regulation, and metabolic processes, including insulin signalling and lipid metabolism, regardless of infection status. Additionally, many DEGs overlapped with previously identified quantitative trait loci (QTLs) associated with resistance to A. salmonicida, providing further insights into the genetic basis of disease resistance.

Discussion

This study represents the first RNA-Seq analysis comparing resistant and susceptible turbot families and contributes valuable knowledge for the development of selective breeding programs targeting disease resistance in turbot and other aquaculture species susceptible to A. salmonicida.
Deepening the understanding of wreck ecology: a comparative study of marine sediment microbiomes across 10 Maltese wreck sites
Authors: Bolton Emma , Greenhalgh Nadine , Kunselman Emily , Mifsud Jasmine , Patel Neem , Sausmekat Maja Pace , Oldach Phoebe , Gambin Timmy
Published: December 2024

The anthropogenic influences of historical shipwrecks on the marine environment remain largely uncharacterized, particularly for wrecks located at depths of ~50 meters and lost over 80 years ago. Below 50 meters, the marine environment transitions from the euphotic to the mesophotic zone, where reduced light, significant changes in oxygen levels, and increased pressure may alter microbial communities and metabolic pathways. Understanding these shifts can provide insights into the adaptation and evolution of microorganisms. Sediment samples were collected by a team of divers from nine wreck sites off the coast of Malta, varying in depth from 5 to 100 meters. All sampling was conducted with the consent and authorization of the Government of Malta for the collection of marine genetic resources. Chemical analyses and metabarcoding techniques were employed to assess how shipwrecks influence microbial diversity and community composition in the surrounding sediments. Alpha (α) diversity of microbial communities was higher in sediments adjacent to the shipwrecks compared to those collected over 100 meters away from any wreck site. Across all nine wreck sites, sediment size emerged as the most significant driver of microbial diversity, followed by frame type and the presence of oil leaks. This study demonstrates that shipwrecks, varying in depth, frame type, and country of origin, significantly influence the microbial ecosystems and sediment chemistry of their surrounding environment. The findings suggest that shipwrecks act as focal points for ecological and chemical changes, contributing to the dynamic interactions between historical artifacts and marine ecosystems.
Second-order sliding mode optimization control of an inverted pendulum system based on fuzzy adaptive technology
Authors: Leng Xuefeng
Published: December 2024

Introduction

This paper aims at the control problem of nonlinear systems with uncertainty in general, and avoids the deviation of sliding mode controller from the preset constraint region during the convergence process.

Methods

A sliding mode control method based on fuzzy adaptive technique was proposed by constructing obstacle Lyapunov function (BLF). Design problem of fuzzy adaptive second-order sliding mode controller considering output constraints. The Lyapunov function of the cutting barrier is designed, and the fuzzy adaptive second-order sliding mode controller is constructed by combining the Lyapunov function with the regression method. A second-order finite output sliding mode controller is designed for the inverted pendulum system. In the case of unknown external disturbance, the mathematical modeling and force analysis of the first order inverted pendulum system are carried out, and the design problem of the fuzzy adaptive second-order sliding mode controller with output restriction is studied.

Results and Discussion

The proposed fuzzy adaptive second-order sliding mode controller has a good control effect in the inverted pendulum system. The fuzzy adaptive second-order controller stabilizes the sliding mode at 0.1 in 1.25 s, while the fuzzy adaptive second-order controller makes the system state reach equilibrium in 15 s. The accuracy of fuzzy adaptive second-order sliding mode controller reaches 99.2%, which is superior to other methods in terms of balance accuracy and recall rate. The controller not only has a fast response speed, but also can effectively suppress system flutter and ensure the rapid stability of the system after constraints. This research method lays a foundation for the design of fuzzy adaptive sliding mode control algorithm.
Challenging perceptions about rural practice using narratives: a living library approach in medical education
Authors: Perez Grace , Malhi Rebecca , Bressler Kamiko , Monaghan Melissa , Johnston Aaron
Published: December 2024

Introduction

The shortage of physicians in rural Canada is a continuing challenge. Canadian medical schools have adapted strategies to increase the supply of rural physicians. This study appraises the effectiveness of the living library (also called Human Library©) in medical education, as an avenue for medical and pre-medical students to engage in dialogue with rural health professionals. Similar to a conventional library, readers check out books, except that “books” are human volunteers willing to share relevant personal experiences, and “readers” are the learners. The reading is the personal interaction between human books and students through narratives of experiences. The program “The Library of Life—Stories of Rural Medicine” (TLoL), was developed to provide students with better understanding of rural life and practice through narratives.

Methods

This is a mixed methods study, using pre- and post-event surveys. Statistical comparisons were done using Wilcoxon and McNemar’s tests. Thematic analysis was used to explore students’ expectations of TLoL and to describe their experience and key takeaways.

Results

Most of the participants were from an urban background, had low familiarity with rural medicine and only 44% would consider a rural career prior to TLoL. After TLoL, improvements were observed in: (i) envisioning rural medicine as career option (p = 0.009), (ii) appreciation of rural living (p = 0.013), (iii) need for rural physicians (p < 0.001). and (iv) rural practice consideration (p = 0.001). Themes from students’ motivations for participation were: (i) students’ curiosity, interest, and (ii) their willingness to engage in dialogue with the human books. Themes from the key takeaways were that TLoL allowed students: (i) to walk in a rural professional’s shoes, enabling them to see “rural” in a new light, and (ii) to self-reflect and gain a sense of personal growth.

Conclusion

Students made gains in attitudes and perceptions toward rural practice. Narratives have the power to challenge held beliefs around rural practice and life, and can encourage students to consider things that traditional medical teaching may not. TLoL can be an effective learning modality in medical education to provide information about rural medicine, in combination with learning opportunities such as rural block rotations and longitudinal clinical clerkship immersions.
Effects of computer-generated patterns with different temporal and spatial frequencies on choroidal thickness, retinal dopamine and candidate genes in chickens wearing lenses
Authors: Liu Hong , Schaeffel Frank , Feldkaemper Marita Pauline
Published: December 2024

Purpose

Changes in choroidal thickness (ChT) are proposed to predict myopia development but evidence is mixed. We investigated time courses of choroidal responses, following different types of dynamic artificial stimulation in chicks with and without spectacle lenses, as well as changes in retinal dopamine metabolism and expression of candidate genes.

Methods

Chicks were kept in an arena surrounded by computer monitors presenting dynamic checkerboard fields of small, medium and large size. Fields were displayed with different cycle frequencies, as ON (rapid rise, slow decay) or OFF (slow rise, rapid decay) temporal luminance profile. Refractive errors, ocular biometry and ChT were assessed. Dopamine metabolism and candidate gene expression levels were also measured. Stimuli were applied for (1) 3 h with no lens, (2) 3 h and monocular treatment with −7D or +7D lenses, (3) 3 or 7 days.

Results

(1) The smallest fields caused the largest decrease in ChT. (2) Negative lens treatment induced on average 11.7 μm thinner choroids. ChT thinning was enhanced by 10 Hz-ON medium field size flicker which also reduced choroidal thickening with positive lenses. (3) With prolonged treatment, the choroid recovered from initial thinning in all groups although to varying degrees which were dependent on stimulus parameters. Relative ChT changes were positively correlated with the vitreal level of dopamine metabolites. Retinal EGR-1 mRNA level was positively correlated with choroidal thickness. Retinal melanopsin mRNA was increased by 10 Hz-ON stimulation and choroidal BMPR1A mRNA increased with 10 Hz-OFF stimulation. On average, early choroidal thinning did not predict the amount of negative lens-induced eye growth changes after 7 days, whereas later ChT changes showed a weak association.

Conclusion

Negative lenses caused long-lasting choroidal thinning, with some recovery during lens wear, especially after stimulation with 10 Hz. The dynamic stimuli modulated choroidal thinning but effects were small. There was little difference between ON and OFF stimulation, perhaps because the checkerboard patterns were too coarse. 10 Hz cycle frequency increased dopamine release. Less dopamine was correlated with thinner choroids. Result do not exclude a predictive value of choroidal thickening for future refractive development since we almost exclusively tested choroidal thinning effects.
Nanotherapy therapy for acute respiratory distress syndrome: a review
Authors: Yu Yilai , Qiu Liping
Published: December 2024

Acute respiratory distress syndrome (ARDS) is a complex and life-threatening disease characterized by severe respiratory failure. The lethality of ARDS remains alarmingly high, especially with the persistent ravages of coronavirus disease 2019 (COVID-19) in recent years. ARDS is one of the major complications of neocoronavirus pneumonia and the leading cause of death in infected patients. The large-scale outbreak of COVID-19 has greatly increased the incidence and mortality of ARDS. Despite advancements in our understanding of the causes and mechanisms of ARDS, the current clinical practice is still limited to the use of supportive medications to alleviate its progression. However, there remains a pressing need for effective therapeutic drugs to combat this devastating disease. In this comprehensive review, we discuss the commonly used therapeutic drugs for ARDS, including steroids, vitamin C, targeted inhibitors, and heparin. While these medications have shown some promise in managing ARDS, there is still a significant gap in the availability of definitive treatments. Moreover, we highlight the potential of nanocarrier delivery systems, such as liposomes, lipid nanoparticles, polymer nanoparticles, and inorganic nanoparticles, as promising therapeutic approaches for ARDS in the future. These innovative delivery systems have demonstrated encouraging results in early clinical trials and offer the potential for more targeted and effective treatment options. Despite the promising early results, further clinical trials are necessary to fully assess the efficacy and safety of nanotherapies for ARDS. Additionally, more in-depth research should be conducted to focus on the continuous development of precision therapies targeting different stages of ARDS development or different triggers. This will provide more ideas and rationale for the treatment of ARDS and ultimately lead to better patient outcomes.
Insight into the microbial diversity and community in the sacrificial pits of Sanxingdui site (Sichuan, China)
Authors: Chen Ruru , Xie Zhenbin , Xiao Qing , Wang Chong , Wen Rui
Published: December 2024

Introduction

The Sanxingdui site (Sichuan, China) is the typical representative of the ancient Shu culture, which lasts from the late Neolithic to early Western Zhou. The sacrificial pits are located in the core region of Sanxingdui site, and numerous artifacts are unearthed including ivory, seashells, bronzes, pottery, jade, stone, gold, bone, and horn products. The function of the pits and buried artifacts has always been the focus, but the microbiome around artifacts attracts less attention. Recently, the microbiome in buried ivory soil has just been identified; however, the microbiome around other artifacts has never been studied. In term of the unique perspective for interpretation the archaeological issues, the study was carried out for: (1) the microbial diversity and community of soil in the lower layer of artifacts in sacrificial pits, (2) the potential biodeterioration behavior of organic and inorganic relics, and (3) the impact of sacrificial and burial activities in different sacrificial pits on microbiome.

Methods

There were 45 soil samples around different artifacts in three sacrificial pits and 12 raw soil samples inside or outside the sacrificial pit sampling from Sanxingdui site. The microbial genomes were then identified and analyzed using the next-generation high-throughput sequencing.

Results

The represented bacterial phyla were Proteobacteria, Actinobacteriota, GAL15, Chloroflexi, Acidobacteriota, Methylomirabilota, Thermoplasmatota, Crenarchaeota, Gemmatimonadota, and Firmicutes, and the represented fungal phyla were Ascomycota, Mortierellomycota, and Basidiomycota. Further microbial functional analysis found that the bacterial genera Sphingopyxis, Limnobacter, and Streptomyces and the fungal genera Cladosporium, Acremonium, and Mortierella were concerned with the degradation of organic matter, while the genera Pseudomonas, Arthrobacter, Variovorax, Aspergillus, and Penicillium might be related to the biocorrosion of bronzes. In addition, the microbial composition and principal co-ordinate analysis (PCoA) demonstrated the significant differences in microbial composition and structure between the raw soil samples and the soil samples around the artifacts and also between the soil samples in different sacrificial pits.

Discussion

It is important to understand the biodeterioration of the buried artifacts and the sacrificial activities in Sanxingdui site according to the results of microbial diversity and community. The combination of microbiology and archaeology will shed light on the archaeological issues related to the ancient human activities and behaviors.
Investigation of functional connectivity differences based on anxiety tendencies
Authors: Oishi Misuzu , Sakurai Noriko , Kawasaki Yuki , Sasaki Kei , Kasai Satoshi , Kodama Naoki
Published: December 2024

Introduction

Anxiety is an emotion necessary for human survival. However, persistent and excessive anxiety can be clinically challenging. Increased anxiety affects daily life and requires early detection and intervention. Therefore, a better understanding of the neural basis of mild anxiety is needed. However, previous studies have focused primarily on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with psychiatric disorders presenting with anxiety. Notably, only a few studies have been conducted on healthy participants, and the relationship between anxiety and functional brain connectivity in the healthy range remains unclear. Therefore, in this study, we aimed to clarify the differences in functional brain connectivity at different degrees of anxiety among healthy participants.

Methods

This study included 48 healthy participants with no history of psychiatric disorders. Participants were administered The General Health Questionnaire (GHQ) 60, a psychological test for assessing anxiety, and the Manifest Anxiety Scale (MAS). The participants then underwent rs-fMRI. Based on the results of each psychological test, the participants were classified into normal and anxiety groups, and the functional connectivity between the two groups was compared using a seed-to-voxel analysis.

Results

Comparison of functional brain connectivity between the normal and anxiety groups classified based on the GHQ60 and MAS revealed differences between brain regions comprising the salience network (SN) in both psychological tests. For the GHQ60, the anxiety group showed reduced connectivity between the right supramarginal gyrus and insular cortex compared with the normal group. However, for the MAS, the anxiety group showed reduced connectivity between the right supramarginal and anterior cingulate cortical gyri compared with the normal group.

Conclusion

Functional connectivity within the SN was reduced in the group with higher anxiety when functional brain connectivity at different anxiety levels was examined in healthy participants. This suggests that anxiety is involved in changes in the functional brain connectivity associated with emotional processing and cognitive control.
Impacts of social isolation stress in safety learning and the structure of defensive behavior during a spatial-based learning task involving thermal threat
Authors: Villalon Stephanie A. , Felix-Ortiz Ada C. , Lozano-Ortiz Kelly , McCarrey John R. , Burgos-Robles Anthony
Published: December 2024

Safety learning during threat and adversity is critical for behavioral adaptation, resiliency, and survival. Using a novel mouse paradigm involving thermal threat, we recently demonstrated that safety learning is highly susceptible to social isolation stress. Yet, our previous study primarily considered male mice and did not thoroughly scrutinize the relative impacts of stress on potentially distinct defensive mechanisms implemented by males and females during the thermal safety task. The present study assessed these issues while considering a variety of defensive behaviors related to safety-seeking, escape, coping, protection, ambivalence, and risk-taking. After a two-week social isolation stress period, mice were required to explore a box arena that had thermal threat and safety zones (5 vs. 30°C, respectively). Since visuospatial cues clearly differentiated the threat and safety zones, the majority of the no-stress controls (69–75%) in both sexes exhibited optimal memory formation for the safety zone. In contrast, the majority of the stress-exposed mice in both sexes (69–75%) exhibited robust impairment in memory formation for the safety zone. Furthermore, while the control groups exhibited many robust correlations among various defensive behaviors, the stress-exposed mice in both sexes exhibited disorganized behaviors. Thus, stress severely impaired the proper establishment of safety memory and the structure of defensive behavior, effects that primarily occurred in a sex-independent manner.
Association between hypothyroidism and obstructive sleep apnea: a bidirectional Mendelian randomization study combined with the geo database
Authors: Zhao Mingyu , Huang Xu , Zheng Hu , Cai Yuhang , Han Wenjia , Wang Yuanyin , Chen Ran
Published: December 2024

Background

The causal relationship between hypothyroidism and obstructive sleep apnea (OSA) remains controversial. Therefore, our research used a bidirectional Mendelian randomization (MR) method in an attempt to determine the causal relationship between hypothyroidism and OSA.

Methods

From the publicly accessible genome-wide association analysis (GWAS) summary database, we obtained single nucleotide polymorphism (SNPs) data pertaining to hypothyroidism and OSA. Inverse variance weighting (IVW) was the principal method of analysis utilized, with validation also conducted via weighted median, MR-Egger, simple model, and weighted model approaches. To further evaluate the robustness of the results, heterogeneity testing, pleiotropy testing, and the “leave-one-out” sensitivity analysis were performed. Differentially expressed genes (DEGs) from the OSA dataset (GSE135917) and hypothyroidism dataset (GSE176153) derived from the Gene Expression Omnibus (GEO) database were screened using the “limma” package. The “clusterProfiler” and “GO plot” packages were used for further enrichment analysis in order to validate the findings of the MR study. The Cytoscape software was utilized to build a protein–protein interaction (PPI) network of DEGs and to screen for hub genes.

Results

The MR analysis showed that genetically predicted hypothyroidism was associated with an increased risk of OSA [IVW odds ratio (OR) = 1.734; 95% confidence interval (CI) = 1.073–2.801; p = 0.025]. The trend of the outcomes of the other approaches is consistent with the trend of the IVW outcome. However, the reverse MR analysis suggested no evidence for the causal effect of OSA on hypothyroidism (IVW OR = 1.002, 95% CI: 0.996–1.009, p = 0.454). The robustness of the results was confirmed by the sensitivity analysis. Bioinformatics analysis revealed that there were DEGs that hypothyroidism and OSA have in common.

Conclusion

Our findings suggested that hypothyroidism may increase the risk of OSA, while the effect of OSA on hypothyroidism was not found in this MR study. Thus, patients with hypothyroidism should be enhanced with screening for OSA for early diagnosis and appropriate treatment.
Dual-stent thrombectomy for recanalization of cerebral embolism caused by infective endocarditis: a case report
Authors: Zhang Haiqi , Chen Jianfei , Chang Wansheng , Lin Feng , Yin Jijun
Published: December 2024

Methods

In this case report, we present an in-depth narrative of a patient who was subjected to mechanical thrombectomy (MT) for an obstruction in the main trunk and bifurcation of the left middle cerebral artery subsequent to Infective Endocarditis (IE). Initial intervention using a solitary-stent technique proved to be ineffective; thus, we shifted to a dual-stent strategy, which successfully recanalized the compromised blood vessel.

Results

The dual-stent retriever method can be especially advantageous for treating persistent clots that occur at arterial bifurcations resisting the efforts of a single-stent retriever during the MT process.

Conclusion

Dual-stent thrombectomy increases the likelihood of clot extraction due to its ability to encompass a larger area of the thrombus within the stent’s framework, potentially improving the clinical outcomes.
Deep learning models for MRI-based clinical decision support in cervical spine degenerative diseases
Authors: Li Kai-Yu , Lu Zhe-Yang , Tian Yu-Han , Liu Xiao-Peng , Zhang Ye-Kai , Qiu Jia-Wei , Li Hua-Lin , Zhang Yu-Long , Huang Jia-Wei , Ye Hao-Bo , Tian Nai Feng
Published: December 2024

Purpose

The purpose of our study is to develop a deep learning (DL) model based on MRI and analyze its consistency with the treatment recommendations for degenerative cervical spine disorders provided by the spine surgeons at our hospital.

Methods

In this study, MRI of patients who were hospitalized for cervical spine degenerative disorders at our hospital from July 2023 to July 2024 were primarily collected. The dataset was divided into a training set, a validation set, and an external validation set. Four versions of the DL model were constructed. The external validation set was used to assess the consistency between the DL model and spine surgeons’ recommendations about indication of cervical spine surgery regarding the dataset.

Results

This study collected a total of 756 MR images from 189 patients. The external validation set included 30 patients and a total of 120 MR images, consisting of 43 images for grade 0, 20 images for grade 1, and 57 images for grade 2. The region of interest (ROI) detection model completed the ROI detection task perfectly. For the binary classification (grades 0 and 1, 2), DL version 1 showed the best consistency with the spine surgeons, achieving a Cohen’s Kappa value of 0.874. DL version 4 also achieved nearly perfect consistency, with a Cohen’s Kappa value of 0.811. For the three-class classification, DL version 1 demonstrated the best consistency with the spine surgeons, achieving a Cohen’s Kappa value of 0.743, while DL version 2 and DL version 4 also showed substantial consistency, with Cohen’s Kappa values of 0.615 and 0.664, respectively.

Conclusion

We initially developed deep learning algorithms that can provide clinical recommendations based on cervical spine MRI. The algorithm shows substantial consistency with experienced spine surgeons.
Development of KCC2 therapeutics to treat neurological disorders
Authors: Kadam Shilpa D. , Hegarty Shane V.
Published: December 2024

KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.g., hyperexcitability and inflammation) converge to impair KCC2-dependent inhibition in CNS. When KCC2 hypofunction occurs, affected neurons are disinhibited due to impaired inhibitory responses to GABA/glycine. This causes neuronal hyperexcitability, disinhibition within neuron circuits, and disrupted neurological functions. More recently, KCC2 was identified as a genetically-validated target for epilepsy, intellectual disability, and autism spectrum disorder, and pathogenic mutations in human SLC12A5 gene were linked to psychiatric/mood disorders. The broad therapeutic utility of KCC2-upmodulating drugs relates to its critical role in determining inhibitory activity of GABAergic neurotransmission, a mechanism widely targeted by several drugs. However, in cases of KCC2 hypofunction GABAergic neurotransmission can be depolarizing/excitatory, thereby impairing endogenous neuronal inhibition while also limiting the effectiveness of existing therapeutics targeting/requiring GABAergic pathway inhibition. Several preclinical reports have shown that KCC2 upmodulating treatments rescue and increase the efficacy of anti-seizure and analgesic medications. Thus, a first-in-class KCC2-potentiating therapy would provide a novel mechanism for restoring physiological CNS inhibition and addressing drug resistance in patients with E/I imbalance pathologies. Herein, we discuss progress toward and further work needed to develop the first-in-class KCC2 therapeutics to treat neurological disorder patients.
Glaucoma and dietary intake: a scoping review
Authors: Edokpa Genesis Daniel , McFarlane Shelly Rose-Marie
Published: December 2024

Introduction

Studies have suggested that dietary intake may influence the incidence and progression of open-angle glaucoma. However, dietary modification is not usually included in the clinical management of glaucoma. The aim of this scoping review was therefore to map the evidence and determine the nature and extent of research done on “diet and glaucoma” and identify any gaps in this area of scholarship.

Materials and methods

A comprehensive search of academic literature was conducted from two relevant electronic databases: PubMed and ScienceDirect. Primary studies that explored the relationship between dietary intake and glaucoma were included if the principal exposure was “diet” and if dietary habits were assessed with dietary questionnaires. The glaucoma outcomes of interest were visual field, retinal nerve fibre layer and/or optic nerve head features.

Results

Nineteen studies were included in the final qualitative synthesis. The dates of publication ranged from 2003 to 2023. About 80% of the studies found some significant associations between glaucoma and dietary intake. However, most studies (95%) were observational, i.e., 7 (37%) used a cross-sectional design, 10 (53%) used a prospective cohort design; and 1 (or 5%) used a nested case–control study design. Only 1 study (or 5%) used a randomized intervention trial. Furthermore, while all studies investigated dietary intake with questionnaires, only 2 studies (or 11%) went further to include assessment of nutritional biomarkers.

Conclusion

Although miscellaneous evidence supports the concept that diet may play a role in glaucoma, most data are unfortunately observational without proven causality, reporting associations from subjective dietary questionnaires. More well-designed studies are required, especially randomized controlled trials that can prove causality.
Pathological features of the differentiation landscape in esophageal squamous cell cancer and their correlations with prognosis
Authors: Deng Jiaying , Zhang Lei , Wang Zezhou , Li Bin , Xiang Jiaqing , Ma Longfei , Zhu Hongcheng , Li Yuan , Zhao Kuaile
Published: December 2024

Background

For esophageal squamous cell carcinoma (ESCC), universally accepted pathological criteria for classification by differentiation degree are lacking. Tumor budding, single-cell invasion, and nuclear grade, recognized as prognostic factors in other carcinomas, have rarely been investigated for their correlation with differentiation and prognosis in ESCC. This study aims to determine if pathological findings can predict differentiation degree and prognosis in ESCC.

Patients and methods

This study reviewed tumor slides from 326 patients who underwent surgery for ESCC between 2007 and 2012. Tumors were evaluated for subtypes, tumor nest size, tumor stroma, and nuclear grade (nuclear diameter and mitosis) across different differentiation groups. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, with group differences assessed using the stratified log-rank test and Cox proportional hazards model.

Results

The mean values of tumor budding invasion margins in well, moderately, and poorly differentiated groups were 25.3%, 30.7%, and 36.3%, respectively. Mean tumor budding/10HPFs were 8.0, 10.3, and 13.0, respectively. Well-differentiated tumors showed more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, more submucosal invasion, and less lymphovascular invasion. Conversely, poorly differentiated tumors exhibited opposite characteristics. Multivariate analyses identified the nuclear diameter as independent prognostic factors for OS and DFS.

Conclusions

Pathological features can stratify the differentiation landscape in ESCC patients. The nuclear diameter (4 lymphocytes) can help predict prognosis in ESCC than other pathological features.

Implications for practice

We first time report the mean values of tumor budding invasion margins and tumor budding/10HPF in well, moderately, and poorly differentiated groups for esophageal squamous cell carcinoma. The landscape of well differentiation was depicted with more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, and less lymphovascular invasion. The nuclear diameter as independent prognostic factors for prognosis. The findings indicate that pathological features can stratify the differentiation landscape in ESCC patients and offer novel insight into definition of well or moderately differentiation.
Improved survival of patients with newly diagnosed oligometastatic prostate cancer through intensified multimodal treatment
Authors: Schütz Viktoria , Nessler Christopher-Leo , Duensing Anette , Zschäbitz Stefanie , Jäger Dirk , Debus Jürgen , Hohenfellner Markus , Duensing Stefan
Published: December 2024

Background and objectives

The standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT), novel antihormonal therapies (NHT) and/or chemotherapy. Patients with newly diagnosed oligometastatic prostate cancer (omPCa) represent a distinct subgroup of mHSPC, for which the optimal treatment, particularly the role of radical prostatectomy (RP) and metastasis-directed therapy (MDT), is currently under debate.

Materials and methods

In this single center, retrospective analysis, 43 patients with newly diagnosed omPCa were included. All patients underwent RP as part of a multimodal, personalized treatment approach. Other treatments included ADT, NHT, MDT (surgery or radiotherapy), adjuvant radiotherapy (prostatic fossa and/or pelvic lymph nodes) or chemotherapy in various combinations. Clinical endpoints were progression free and cancer specific survival (PFS, CSS).

Results

No patient with omPCa died from prostate cancer during an up to ten years follow-up period after intensified multimodal treatment i.e., RP, ADT, adjuvant radiation therapy and MDT (n=13). In contrast, patients requiring chemotherapy (n=10) showed a significantly worse PFS (p<0.001) and CSS (p<0.001). Patients receiving various combinations (<4 therapeutic modalities; n=20) showed a more favorable outcome than patients receiving chemotherapy, but differences in PFS and CSS were not statistically significant compared to patients receiving an intensified multimodal treatment.

Conclusions

An intensified, multimodal treatment approach including RP can lead to excellent survival outcomes in patients with newly diagnosed omPCa. Patients requiring chemotherapy have most likely a more aggressive disease and therefore a more rapid tumor progression. Future studies to identify markers for risk stratification in patients with omPCa are therefore needed.
Prevalence of FLT3 gene mutation and its expression in Brazilian pediatric B-ALL patients: clinical implications
Authors: Biojone Estefânia Rodrigues , Guido Bruna Cândido , Cavalcante Larissa Lemos Mendanha , Santos Júnior Agenor de Castro Moreira dos , Pontes Robéria Mendonça de , Furtado Felipe Magalhães , Córdoba José Carlos , Magalhães Isis Maria Quezado , de Oliveira Diêgo Madureira , Camargo Ricardo
Published: December 2024

Introduction

There is consistent evidence that FLT3 may be a driver gene in B-ALL and that selected cases may benefit from the use of FLT3 inhibitors. Our study was conducted to evaluate the frequency and types of FLT3 mutations in pediatric patients with B-ALL, the relative expression of this gene, and their influence on clinical evolution.

Methods

We evaluated 156 children with B-ALL treated between July 2018 and September 2023. Screening for FLT3 mutations was performed using RFLP and fragment analysis, while FLT3 expression was assessed by qPCR.

Results

FLT3-TKD and/or FLT3-JM-INDEL mutations were found in 8 patients (5.1%). We did not identify any ITD-type mutations. None of the patients with identified FLT3 mutations presented recurrent rearrangements in B-ALL or alterations in the IKZF1, PAX5, or ERG genes, suggesting that FLT3 mutation may serve as the driving mechanism for leukemia in these cases. Two (2/8) patients with FLT3 mutations experienced disease relapse. Although we did not observe FLT3 overexpression among patients with FLT3 mutations, FLT3 expression levels were higher in these patients compared to WT patients. Four FLT3-WT patients presented FLT3 overexpression, defined as RQ > 10. FLT3 mutations or overexpression were not associated with relapses or survival rates.

Discussion

Our findings do not support the inclusion of FLT3 as a routine marker in the risk stratification of B-ALL patients; nevertheless, FLT3 alterations may be relevant for guiding personalized treatment approaches in specific clinical contexts.