bluuebunny/crossref_metadata_2025 huggingface dataset:
ProC6C, a novel multi-stage malaria vaccine, elicits functional antibodies against the minor and central repeats of the Circumsporozoite Protein in human adults
Authors: Plieskatt Jordan , Ofori Ebenezer Addo , Naghizadeh Mohammad , Miura Kazutoyo , Flores-Garcia Yevel , Borbye-Lorenzen Nis , Tiono Alfred B. , Skogstrand Kristin , Sagara Issaka , Zavala Fidel , Theisen Michael
Published: November 2024

Introduction

ProC6C is a multi-stage malaria vaccine which includes Plasmodium falciparum Circumsporozoite Protein (PfCSP), Pfs48/45 and Pfs230 sequences, designed to elicit functional antibodies that prevent sporozoite invasion of human hepatocytes (PfCSP) and parasite development in mosquitoes (Pfs48/45 and Pfs230). ProC6C formulated on Alhydrogel was evaluated in combination with Matrix-M in a Phase 1 trial in Burkina Faso. The PfCSP antibody responses were assessed for magnitude, specificity, avidity and functionality. These results compliment the prior reported safety and tolerability of ProC6C as well as the transmission reducing activity of ProC6C.

Methods

The PfCSP response of ProC6C in Burkinabes in the Phase 1 trial (PACTR202201848463189) was profiled through the three vaccine administrations of 100 µg protein on Alhydrogel® alone (AlOH) or combined with 50 µg Matrix-M™ adjuvant (AlOH/Matrix-M). Serology was completed against full-length PfCSP and major/minor repeat peptides using antibody equivalence to PfCSP monoclonal antibodies (mAb 311, mAb 317 and mAb L9). Comparison of the ProC6C responses were made to those that received RTS,S/AS01 in a study conducted in Thailand. Bio-Layer Interferometry was further used to determine antibody avidity. The human IgG was subsequently purified, pooled, and evaluated in a mouse sporozoite challenge model to determine functionality.

Results

A single administration of ProC6C-AlOH/Matrix-M seroconverted 19 of 20 volunteers against PfCSP and significantly enhanced antibody titers to major and minor repeats (and present through D180). At D70, ProC6C-AlOH/Matrix-M PfCSP antibodies were found to be similar to responder pools generated from Thai adults receiving RTS,S/AS01. Additionally, ProC6C antibodies were found to be competitive to established PfCSP antibodies such as mAb 317 and mAb L9. The purified and pooled IgG from human volunteers, used in a passive transfer mouse sporozoite challenge model, showed a median of 50% inhibition (P=0.0058). ProC6C PfCSP antibodies were functional in this in vivo assessment and consistent with inhibition seen by other Circumsporozoite vaccines in this model.

Discussion

This analysis supports continued investigation of the antibody responses elicited by the ProC6C multi-stage malaria vaccine. This Phase 1 clinical trial demonstrated the short PfCSP sequence included in ProC6C can induce significant PfCSP antibodies in humans, which importantly were determined to be functional.
Local radiotherapy in extensive-stage small-cell lung cancer sustainably boosts the clinical benefit of first-line immunotherapy: a case report
Authors: Wang Hongming , Wang Nuoni , Li Shiyan , Du Yangfeng , Wu Tao , Tian Wei , Dong Wen , Liu Xiaoyang , Zhang Yan , Zheng Jiang , Xiao Zemin , Wu Zhijun
Published: November 2024

Background

Extensive-stage small-cell lung cancer (ES-SCLC) has a dismal prognosis owing to its high aggressiveness, rapid drug resistance, and early metastasis. ES-SCLC responds well to first-line chemotherapy, and chemotherapy coupled with immunotherapy can further improve overall survival. However, the long-term survival of patients remains unsatisfactory because of its high recurrence rate and the poor efficacy of second-line treatment. Although local radiotherapy is an important component of the overall treatment for ES-SCLC, its value in the age of immunotherapy remains controversial.

Case description

A 54-year-old male with ES-SCLC achieved a complete response (CR), as determined using enhanced computed tomography (CT) after four cycles of immunochemotherapy (serplulimab, carboplatin, and etoposide). Whole-body positron emission tomography-CT was performed during maintenance treatment with serplulimab, which showed primary lung, liver, and bone metastatic lesions with CR. However, several mediastinal lymph nodes exhibited glucose metabolism uptake, and new lesions appeared on the head. The patient underwent palliative radiotherapy of the head and consolidative thoracic radiotherapy of the chest and continued maintenance treatment with serplulimab. Subsequent magnetic resonance imaging of the head suggested good control of metastatic lesions (CR). The patient received first-line immunotherapy for approximately 20 months.

Conclusions

This report presents a patient with ES-SCLC who underwent local radiotherapy in addition to serplulimab as maintenance therapy. Although the programmed death-ligand 1 (PD-L1) expression level was negative and a PD-1 inhibitor instead of a PD-L1 inhibitor was used, the patient did not experience significant pneumonia during treatment, and the efficacy of the current treatment was evident. This treatment model warrants further clinical investigation.
COVID-19 vaccine and the risk of flares in inflammatory arthritis: a systematic literature review and meta-analysis
Authors: Hoxha Ariela , Striani Giovanni , Lovisotto Marco , Simioni Paolo , Doria Andrea , Ramonda Roberta
Published: November 2024

Introduction

Coronavirus disease 2019 (COVID-19) vaccines aroused concerns about the risk of flares and adverse events in inflammatory arthritis (IA) since the vaccine clinical trials did not specifically investigate this subset of patients.

Methods

A systematic literature review and meta-analysis to summarize the data on joint disease flare and adverse events following immunization (AEFI). Two researchers independently evaluated the literature on Pubmed, Scopus, and EMBASE databases from 22nd March 2020 to 30th September 2023. A random-effects model was used to pool odds ratios (OR) (with 95% CI) for the risk of joint disease flares and adverse events. Subgroup analyses were performed to evaluate the risk of disease flare between different IA and adverse events. Heterogeneity was assessed by I2 statistic.

Results

A total of 9874 IA patients were included in the study: 6579 (66.6%) patients affected by RA and 3295 (33.4%) spondyloarthritis (SpA). The overall rate of flares was higher in RA vs. SpA (9.1% vs. 5.3%). However, the pooled estimated analysis showed no increased risk of joint disease flare following COVID-19 vaccination in patients affected by RA vs. SpA [OR 0.88, 95% CI: 0.77-1.00]. Furthermore, a subgroup analysis showed an increased risk of joint flares in psoriatic arthritis (PsA) patients vs. RA [OR 0.79, 95% CI: 0.68-0.93, p=0.004]. The pooled estimated analysis revealed no increased risk of AEFI in patients with RA vs. SpA [1.02, 95% CI: 0.63-1.65].

Conclusions

Our meta-analysis summarized the current evidence on joint disease flares and COVID-19 vaccine-associated AEFI in IA patients. Pooled analysis showed an increased risk of disease flares in PsA vs. RA patients.
Intraspecific variation in resilience traits of eelgrass across intertidal stress gradients and oyster aquaculture methods
Authors: Ruesink Jennifer L. , Houle Katie , Kroeker Kristy J. , Dumbauld Brett R. , Boardman Fiona C. , Lewis Nathaniel S. , McIntyre Brooke A. , Suhrbier Andrew D. , Hudson Bobbi
Published: November 2024

Species persist through resistance and recovery traits induced by natural stressors. Whether human activities exacerbate or moderate the effects of natural stressors is an open question. Because eelgrass (Zostera marina) creates coastal habitat, its response to natural stressors and human activities is of particular management importance. In this study, traits of intertidal eelgrass were examined across cumulative stressors of emersion and oyster culture, including two culture types: oysters grown directly on sediment (ground culture) or supported by gear above the sediment (off-bottom culture). Summer eelgrass was larger above- and below-ground and branched less than in spring, while density and cover were similar seasonally but declined at higher elevation and in ground culture. Eelgrass traits were divided into those related to resistance (larger above-ground size and below-ground storage) and recovery (increased flowering, branching, and rhizome extension). Resistance traits responded additively to intertidal elevation and oyster culture, with above- and below-ground size reduced in all conditions except that rhizome mass was maintained in ground culture. Smaller above-ground size may confer resistance to emersion stress, as a departure from expectations for other stressors. For resilience traits, flowering increased and internode length declined at higher elevation, whereas these traits did not change in ground culture, and off-bottom culture was associated with shorter internodes (additive cumulative stressor) and tended to moderate the enhanced flowering at higher elevations (non-additive, P=0.058). Transitory disturbance in ground culture may reduce eelgrass density with few effects on resilience, whereas off-bottom culture involves longer-term gear placement and trait responses by eelgrass.
Multiple recommended health behaviors among medical students in Western Canada: a descriptive study of self-reported knowledge, adherence, barriers, and time use
Authors: Ip Nathanael , Scarrott Kendra , Conklin Annalijn I.
Published: November 2024

Background

General medical practitioners are responsible for promoting and prescribing lifestyle modification and serve as role models for healthy behaviors. We aimed to assess self-reported knowledge, adherence, barriers and time spent on all recommended health behaviors among medical students.

Methods

A cross-sectional online survey of eight behavioral domains among undergraduate medical students in The University of British Columbia, Canada, was analysed using descriptive statistics and visual display.

Results

Between March and April 2023, 137 medical students participated in the survey (74% female). Over 80% had knowledge of five health behavior recommendations, but lacked knowledge of specific dietary recommendations in particular. Over 60% reported meeting guideline-recommended levels for tobacco, weekly alcohol, daily alcohol (females only), and physical activity (males only). Large gaps existed between knowledge and adherence for physical activity, sleep, sedentariness, screen time, and dietary recommendations. Sex differences in knowledge and adherence to recommended health behaviors were identified. Time spent on wellness focused on sleep (47–49 h/week), diet (9.6 h/week), exercise (5.8 h/week), and hobbies (6.1 h/week). Forgetting recommendations (69% of females, 71% of males), and lack of time (72% of females, 52% of males) were principal barriers to knowledge and adherence.

Conclusion

Most medical students in Western Canada reported not meeting multiple recommended health behaviors. Time was the largest barrier to adherence and free time was spent on sleep. Medical education may require protected time and dedicated content for health behaviors to ensure future physicians can be role models of health promotion for patients.
Subphenotypic features of patients with sepsis and ARDS: a multicenter cohort study
Authors: Li Nan , Fang DeYu , Ge Feng , Zhang Lin , Liu Ying , Jin Hongxu , Shen Hao , Xie Keliang , Gao Yan
Published: November 2024

Objectives

Patients with sepsis are often comorbid with acute respiratory distress syndrome (ARDS), and the phenotypic characteristics of pulmonary and non-pulmonary infections leading to ARDS are still unclear. This study aimed to compare the phenotypic characteristics of ARDS resulting from pulmonary infections and other non-site infections and provide better guidance for clinical treatment.

Methods

We conducted a multicenter cohort analysis using data from the Tianjin Medical University General Hospital, Medical Information Mart for Intensive Care-IV (MIMIC-IV), and the electronic intensive care unit (eICU) databases. The study population consisted of adult patients diagnosed with sepsis and ARDS. The primary objectives were to compare the characteristics and outcomes of patients with pulmonary infection-induced ARDS and those with non-pulmonary infection-induced ARDS using Wilcoxon analysis, Kaplan–Meier curves, correlation analysis, propensity matching scores, and other statistical methods.

Results

Patients with ARDS by pulmonary infection may be more likely to have a history of chronic obstructive pulmonary disease, and abdominal infection was more likely to induce ARDS in sepsis patients with non-pulmonary infection. Pulmonary infections caused by Klebsiella pneumoniae and Acinetobacter baumannii were more likely to induce ARDS. The oxygenation index and prognosis of ARDS patients induced by pulmonary infection were worse than those caused by other infections, with lower PaO2, PaO2/FiO2, and ROX index and longer hospital stay. More ARDS patients with pulmonary infection were given mechanical ventilation therapy, with higher mortality, APACHE II, SOFA, and SAPS II. The further correlation analysis showed that the prognostic scores of ARDS patients were negatively correlated with PaO2/FiO2 and ROX index. The above results were confirmed to varying degrees by propensity matching scores, external cohort validation, and other methods.

Conclusion

Pulmonary infection induces a worse prognosis of ARDS than other site infections in patients with sepsis and ARDS. These patients require heightened vigilance, early intervention, and possibly more aggressive management strategies.
A study of machine learning to predict NRDS severity based on lung ultrasound score and clinical indicators
Authors: Huang Chunyan , Ha Xiaoming , Cui Yanfang , Zhang Hongxia
Published: November 2024

Objective

To develop predictive models for neonatal respiratory distress syndrome (NRDS) using machine learning algorithms to improve the accuracy of severity predictions.

Methods

This double-blind cohort study included 230 neonates admitted to the neonatal intensive care unit (NICU) of Yantaishan Hospital between December 2020 and June 2023. Of these, 119 neonates were diagnosed with NRDS and placed in the NRDS group, while 111 neonates with other conditions formed the non-NRDS (N-NRDS) group. All neonates underwent lung ultrasound and various clinical assessments, with data collected on the oxygenation index (OI), sequential organ failure assessment (SOFA), respiratory index (RI), and lung ultrasound score (LUS). An independent sample test was used to compare the groups’ LUS, OI, RI, SOFA scores, and clinical data. Use Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify predictor variables, and construct a model for predicting NRDS severity using logistic regression (LR), random forest (RF), artificial neural network (NN), and support vector machine (SVM) algorithms. The importance of predictive variables and performance metrics was evaluated for each model.

Results

The NRDS group showed significantly higher LUS, SOFA, and RI scores and lower OI values than the N-NRDS group (p < 0.01). LUS, SOFA, and RI scores were significantly higher in the severe NRDS group compared to the mild and moderate groups, while OI was markedly lower (p < 0.01). LUS, OI, RI, and SOFA scores were the most impactful variables for the predictive efficacy of the models. The RF model performed best of the four models, with an AUC of 0.894, accuracy of 0.808, and sensitivity of 0.706. In contrast, the LR, NN, and SVM models have lower AUC values than the RF model with 0.841, 0.828, and 0.726, respectively.

Conclusion

Four predictive models based on machine learning can accurately assess the severity of NRDS. Among them, the RF model exhibits the best predictive performance, offering more effective support for the treatment and care of neonates.
Comparison of tissue damage and inflammation for robotic laparoscopy and conventional laparoscopy in early endometrial cancer
Authors: Meng Shengnan , Cao Yanling , Shen Qingwei , Dong Ling , Wang Nan
Published: November 2024

Introduction

This study was to analyze the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between robotic laparoscopy and conventional laparoscopy in early endometrial cancer.

Methods

In a randomized controlled trial conducted at SHANGHAI FIRST MATERNITY and INFANT HOSPITAL, eighty women with early-stage, low-risk endometrial cancer were randomly assigned to receive either robotic or conventional laparoscopy. Blood samples were collected at admission, immediately before surgery, 2 h after surgery, 24 h after surgery, 48 h after surgery, and 1 week after surgery. The samples were analyzed for various biomarkers associated with inflammatory processes and tissue damage. These included high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), platelet count, interleukin-6 (IL-6), cortisol, creatine kinase (CK), and tumor necrosis factor-alpha (TNF-α). These markers provide insights into the underlying physiological responses and potential tissue-level changes within the study participants.

Results

There was no significant difference in clinical and preoperative data between two groups. The results showed that the patients who underwent robotic laparoscopy had a longer pre-surgical time compared to the conventional laparoscopy group. However, the robotic group had shorter operating times, quicker vaginal cuff closures, and lower estimated blood loss compared to the conventional laparoscopy group. The hospital stays, Visual Analog Scale (VAS) score and drainage volume on the first day after operation were lower in robotic group compared to conventional laparoscopy group. hs-CRP, WBC, IL-6 and cortisol were significantly lower in the robotic group, though the differences were transient.

Discussion

This study demonstrated that robotic laparoscopy, used in early endometrial cancer treatment, leads to a reduced inflammatory response, less tissue damage, and lower stress levels, as evidenced by decreased levels of hs-CRP, IL-6, and cortisol, compared to conventional laparoscopy. These findings suggest that robot- laparoscopy may facilitate a quicker recovery and improve patient-reported outcomes.
Antimicrobial peptide AMP-17 induces protection against systemic candidiasis and interacts synergistically with fluconazole against Candida albicans biofilm
Authors: Sun Chaoqin , Zhu Lijuan , Yang Longbing , Tian Zhuqing , Jiao Zhenlong , Huang Mingjiao , Peng Jian , Guo Guo
Published: November 2024

Candida albicans, a common commensal and opportunistic fungal pathogen in humans, can occasionally progress to disseminated candidiasis which is a serious condition with a high morbidity and fatality rate. The emergence of drug-resistant fungal strains compels us to look for an efficient treatment solution. Our earlier studies have demonstrated that the unique antimicrobial peptide AMP-17 from Musca domestica has a strong antifungal impact on C. albicans in vitro. Here, we verified the therapeutic effects of AMP-17 on systemic candidiasis in vivo and the peptide interacts with fluconazole, a common antifungal medication, to treat systemic candidiasis. In the disseminated candidiasis model of Galleria mellonella and mice challenged with C. albicans, AMP-17 increased the survival rates of infected larvae and mice to 66.7 and 75%, respectively. Furthermore, the peptide lowered the load of C. albicans in the infected larvae and the kidneys of the mice by nearly 90%. Additional histological examination and measurements of plasma cytokines showed that the injection of AMP-17 markedly reduced the inflammatory response and balanced cytokine expression. Furthermore, checkerboard micro dilution experiments demonstrated that AMP-17 and fluconazole worked in synergy to inhibit C. albicans in the biofilm mode. According to morphological studies, AMP-17 and fluconazole together decreased the production of hyphae throughout the C. albicans biofilm formation process, loosening the mature biofilms’ structure and lowering the amount of carbohydrates in the extracellular matrix (ECM) of the biofilms. Taken together, these results showed that AMP-17 would be a viable treatment for systemic candidiasis and might be a different approach to combating Candida biofilm, either by itself or in conjunction with fluconazole.
Exploring agro-ecological significance, knowledge gaps, and research priorities in arbuscular mycorrhizal fungi
Authors: Mwampashi Lenganji Lackson , Magubika Aneth Japhet , Ringo Job Frank , Theonest Dickson J. , Tryphone George Muhamba , Chilagane Luseko Amos , Nassary Eliakira Kisetu
Published: November 2024

This systematic review examines the global agricultural relevance and practical environmental implications of arbuscular mycorrhizal fungi (AMF) within the phylum Glomeromycota. Following PRISMA guidelines, ensuring a comprehensive and unbiased literature review, a literature search was conducted, focusing on the functional roles of AMF in enhancing crop productivity, nutrient uptake, and soil health. Key findings reveal that AMF contribute significantly to sustainable agriculture by reducing the need for chemical fertilizers and increasing plant resilience to environmental stressors like drought, salinity, or pest resistance. The review highlights the importance of AMF in forming symbiotic relationships with plants, which enhance nutrient absorption and improve soil structure, showcasing long-term benefits such as reduced erosion or improved water retention. However, the current literature lacks in-depth exploration of the taxonomy and evolutionary aspects of AMF, as well as the specific functional roles they play in different agricultural contexts, e.g., understanding evolution could enhance strain selection for specific crops. This review identifies several urgent research gaps, including a need for a more refined understanding of AMF community dynamics under varying land management practices. For example, there are gaps in and a critical evaluation of advanced molecular techniques. Such techniques are essential for studying these interactions. Addressing these gaps will enhance the integration of AMF into sustainable agricultural systems and improve ecosystem management practices across different geographical regions. Future research should prioritize developing precise molecular imaging techniques and optimizing AMF applications for different crops and soil types to maximize their ecological and agricultural benefits. This could be practical through interdisciplinary collaboration (e.g., involving molecular biologists, agronomists, etc.). In conclusion, this review advances the practical application of AMF in agriculture and its contribution to biodiversity conservation in agroecosystems. Integrating these findings into policy frameworks could encourage sustainable farming practices, promote the adoption of AMF inoculants, and foster incentives for environmentally friendly land management strategies.

Systematic review registration

https://www.bmj.com/content/372/bmj.n71.
High-altitude environments enhance the ability of Eothenomys miletus to regulate body mass during food limitation, with a focus on gut microorganisms and physiological markers
Authors: Zhang Tianxin , Jia Ting , Zhu Wanlong , Fan Lixian
Published: November 2024

Animals’ digestion, energy metabolism, and immunity are significantly influenced by interactions between the gut microbiota and the intestinal environment of the host. Previous studies have shown that gut microbiota of Eothenomys miletus can respond to environmental changes, high fiber or fat foods. But how E. miletus in high-altitude adapt to their environment through gut microbiota and physiological changes during winter food shortages period was unclear. In the present study, we evaluated the altitude differences in gut microbiota and their interactions with physiology in terms of body mass regulation in order to study the adaptation of the gut microbiota and physiological indicators of the E. miletus under food restriction settings. E. miletus were collected for this study from Jingdong County (JD, low-altitude) and Xianggelila County (XGLL, high-altitude) in Yunnan Province, China, and split into three groups: control group, food-restricted feeding group for 7 days, and re-feeding group was offered a standard diet for 14 days. 16S rRNA gene sequencing and physiological methods were used to analyze the abundance and community structure of gut microbiota, as well as physiological indicators of each group in E. miletus. The results showed that while the RMR changed more during the period of food restriction, the body mass and major organ masses of E. miletus from high-altitude changed less. After food restriction, RMR in XGLL decreased by 25.25%, while that of in JD decreased by 16.54%. E. miletus from the XGLL had gut bacteria that were more abundant in Firmicutes and had fewer OTUs, and the microbiota had a closer interaction with physiological indicators. Moreover, the gut microbiota adapted to the food shortage environment by enhancing the genera of Bacterroides, Ruminococcus, Turicibacter, and Treponema to improve the utilization of nutrient resources. The interactions between microbial species and the equilibrium of energy homeostasis were further impacted by alterations in physiological indicators and microbial community structure. These variations were important for E. miletus to adapt to the fluctuations and changes of food resources in high-altitude region, which also expand our knowledge of organismal adaptations and the mechanisms behind the interactions between gut bacteria and host physiology.
Predictive model for aminoglycoside induced ototoxicity
Authors: Adeyemo Adebolajo A. , Adeolu Josephine , Akinyemi Joshua O. , Omotade Olayemi O. , Oluwatosin Odunayo M.
Published: November 2024

Background

Irreversible hearing loss is a well-known adverse effect of aminoglycosides, however, inability to accurately predict ototoxicity is a major limitation in clinical care. We addressed this limitation by developing a prediction model for aminoglycoside ototoxicity applicable to the general population.

Methods

We employed a prospective non-drug-resistant tuberculosis (TB), non-HIV/AIDS cohort of 153 adults on Streptomycin based anti-TB therapy. High frequency pure-tone audiometry was done at regular intervals throughout the study. Clinical and audiological predictors of ototoxicity were collated and ototoxic threshold shift from the baseline audiogram computed. The prediction model was developed with logistic regression method by examining multiple predictors of ototoxicity. Series of models were fitted sequentially; the best model was identified using Akaike Information Criterion and likelihood ratio test. Key variables in the final model were used to develop a logit model for ototoxicity prediction.

Results

Ototoxicity occurred in 35% of participants. Age, gender, weight, cumulative Streptomycin dosage, social class, baseline pure tone average (PTA) and prior hearing symptoms were explored as predictors. Multiple logistic regression showed that models with age, cumulative dosage and baseline PTA were best for predicting ototoxicity. Regression parameters for ototoxicity prediction showed that yearly age increment raised ototoxicity risk by 5% (AOR = 1.05; CI, 1.01–1.09), and a gram increase in cumulative dosage increased ototoxicity risk by 7% (AOR = 1.05; CI, 1.05–1.12) while a unit change in baseline log (PTA) was associated 254% higher risk of ototoxicity (AOR = 3.54, CI: 1.25, 10.01). Training and validation models had area under the receiver operating characteristic curve as 0.84 (CI, 0.76–0.92) and 0.79 (CI, 0.62–0.96) respectively, showing the model has discriminatory ability.

Conclusion

This model can predict aminoglycoside ototoxicity in the general population.
Consistent genes associated with structural changes in clinical Alzheimer’s disease spectrum
Authors: Lu Yingqi , Zhang Xiaodong , Hu Liyu , Cheng Qinxiu , Zhang Zhewei , Zhang Haoran , Xie Zhuoran , Gao Yiheng , Cao Dezhi , Chen Shangjie , Xu Jinping
Published: November 2024

Background

Previous studies have demonstrated widespread brain neurodegeneration in Alzheimer’s disease (AD). However, the neurobiological and pathogenic substrates underlying this structural atrophy across the AD spectrum remain largely understood.

Methods

In this study, we obtained structural MRI data from ADNI datasets, including 83 participants with early-stage cognitive impairments (EMCI), 83 with late-stage mild cognitive impairments (LMCI), 83 with AD, and 83 with normal controls (NC). Our goal was to explore structural atrophy across the full clinical AD spectrum and investigate the genetic mechanism using gene expression data from the Allen Human Brain Atlas.

Results

As a result, we identified significant volume atrophy in the left thalamus, left cerebellum, and bilateral middle frontal gyrus across the AD spectrum. These structural changes were positively associated with the expression levels of genes such as ABCA7, SORCS1, SORL1, PILRA, PFDN1, PLXNA4, TRIP4, and CD2AP, while they were negatively associated with the expression levels of genes such as CD33, PLCG2, APOE, and ECHDC3 across the clinical AD spectrum. Further gene enrichment analyses revealed that the positively associated genes were mainly involved in the positive regulation of cellular protein localization and the negative regulation of cellular component organization, whereas the negatively associated genes were mainly involved in the positive regulation of iron transport.

Conclusion

Overall, these results provide a deeper understanding of the biological mechanisms underlying structural changes in prodromal and clinical AD.
Nomogram model based on clinical factors and autonomic nervous system activity for predicting residual renal function decline in patients undergoing peritoneal dialysis
Authors: Wang Jing , Chen Zhenye , Huang Yaoyu , Qian Yujun , Cui Hongqing , Zhang Li , Zhang Yike , Wang Ningning , Chen Hongwu , Ren Haibin , Mao Huijuan
Published: November 2024

Background

Several heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.

Methods

Patients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.

Results

Ninety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.

Conclusion

The nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.
Early-life undernutrition in the great Chinese famine and the risk of early natural menopause: a retrospective cohort study in Western China
Authors: Xu Xiaoyang , Zhang Yong , Qi Xiaoya
Published: November 2024

Purpose

Early age of menopause may increase the risk of fracture, cardiovascular diseases, and all-cause mortality. This study aimed to investigate the relation between early-life undernutrition in the Great Chinese Famine and the risk of early natural menopause.

Methods

A famine exposure retrospective cohort was established during 2017–2018. Postmenopausal women who were born on 01 October 1956–30 September 1964 and came to the hospital for routine health examinations were candidates for the study. Famine time was defined from 1 January 1959 to 31 December 1961. Three types of early-life famine exposure status were determined by the participant’s date of birth. Natural menopause age below 45 was defined as early menopause. The association between early-life famine exposure status and the risk of early natural menopause was confirmed by multiple logistic regression.

Result

A total of 3,337 participants born around famine were included in this study. The prevalence of early menopause was 13.1, 10.0, and 8.3% for those born before, during, and after the famine, respectively. The multiple logistic regression showed that women born before famine significantly increased the risk of early menopause compared to non-exposure (born after famine) (the fully adjusted OR = 1.463, 95%CI = 1.049–2.042). The fetal famine exposure did not significantly increase the risk of early menopause (the fully adjusted OR = 1.244, 95%CI = 0.878–1.764).

Conclusion

Long-term early childhood famine exposure, which caused chronic undernutrition at young ages, increased the risk of early menopause. Early lifetime undernutrition can be recognized as an adverse factor in female reproductive development and aging. This cohort study further confirmed the hypothesis of developmental origins of health and disease from the aspect of women’s reproductive health. Further mechanism study is warranted.
Association between major dietary patterns and obesity phenotypes in southwest China: baseline survey results from Hechuan
Authors: Shaomei Wang , Dezhi Jing , Mengfen Li , Huaan Duan , Xianbin Ding , Juan Peng , Xia Li , Yanfeng Zhu
Published: November 2024

Background

This study aimed to identify the main dietary patterns in Hechuan and clarify how they are associated with obesity phenotypes.

Methods

A cross-sectional study was conducted based on a baseline survey of a general population cohort study in southwest China. A semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary habits of the participants in the past year. Principal component analysis was conducted to identify the main dietary patterns, and multinomial logistic regression analysis was conducted to describe the association between the major dietary patterns and obesity phenotypes.

Results

Three major dietary patterns were identified. The participants who followed the wheaten food dietary pattern had a higher likelihood of having metabolically normal obesity (MHO) (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.02–1.08), metabolically abnormal normal weight (MUNW) (OR 1.08, 95%CI 1.00–1.16), and metabolically abnormal obesity (MUO) (OR 1.07, 95%CI 1.04–1.11). Specifically, those with the highest wheaten food dietary pattern were 1.60 times more likely to have MHO (OR 1.60, 95%CI 1.25–2.05), 2.62 times more likely to have MUNW (OR 2.62, 95%CI 1.28–5.37), and 2.01 times more likely to have MUO (OR 2.01, 95%CI 1.51–2.69) than those with the lowest wheaten food dietary pattern.

Conclusion

The wheaten food dietary pattern may increase the risk of obesity and metabolic abnormalities. Therefore, timely interventions should be carried out for this group of people.
Donor human milk: the influence of processing technologies on its nutritional and microbial composition
Authors: Conboy-Stephenson Ruth , Ross R. Paul , Kelly Alan L. , Stanton Catherine
Published: November 2024

Human milk is regarded as the gold standard nutrition for newborn infants, providing all nutrients required for adequate growth and development from birth to 6 months. In addition, human milk is host to an array of bioactive factors that confer immune protection to the newborn infant. For this reason, the supply of human milk is crucial for premature, seriously ill, or low birth weight infants (<1,500 g). When a mother’s own milk is unavailable, donor human milk is the recommended alternative by the World Health Organization. Prior to consumption, donor human milk undergoes pasteurization to ensure the eradication of bacterial agents and prevent the transfer of potentially pathogenic organisms. Currently, Holder Pasteurization, a heat-based treatment, is the widely adopted pasteurization technique used by milk banks. Holder pasteurization has demonstrated degradative effects on some of milk’s biologically active factors, thus depleting critical bioactive agents with known functional, protective, and beneficial properties, ultimately reducing the immunoprotective value of donor human milk. As a result, alternative strategies for the processing of donor human milk have garnered much interest. These include thermal and non-thermal techniques. In the current review, we describe the effects of Holder pasteurization and alternative milk processing technologies on the nutritional and bioactive properties of milk. In addition, the capacity of each technique to ensure microbial inactivation of milk is summarized. These include the most extensively studied, high-temperature short-time and high-pressure processing, the emerging yet promising techniques, microwave heating and UV-C irradiation, and the lesser studied technologies, thermoultrasonication, retort processing, pulsed electric field, and gamma irradiation. Herein, we collate the findings of studies, to date, to allow for greater insight into the existing gaps in scientific knowledge. It is apparent that the lack of a cohesive standardized approach to human milk processing has resulted in contrasting findings, preventing a direct comparative analysis of the research. We conclude that donor human milk is a unique and valuable resource to the health sector, and although substantial research has been completed, persistent data disparities must be overcome to ensure optimal nutrition for the vulnerable newborn preterm infant group, in particular.
Comparison of 68Ga-PSMA PET and mpMRI for prostate cancer local staging: a comprehensive review and direct meta-analysis
Authors: Jin Xinyu , Cai Yijie , Ren Xiaolu
Published: November 2024

Purpose

This meta-analysis is conducted to evaluate the comparative diagnostic efficacy of 68Ga-PSMA PET vs. mpMRI in detecting local staging of prostate cancer(PCa).

Methods

A comprehensive search was conducted in the PubMed and Embase databases to identify publications up to February 2024. The analysis included studies that evaluated the direct comparison of 68Ga-PSMA PET and mpMRI for local staging of prostate cancer. The reliability of the analyzed studies was evaluated using the QUADAS-2 tool.

Results

The meta-analysis included 10 articles involving 505 patients, which revealed that both 68Ga-PSMA PET and mpMRI had similar sensitivities and specificities in detecting extracapsular extension(ECE) and seminal vesicle invasion(SVI). The sensitivities for ECE were 0.56 (95% CI: 0.41-0.71) for 68Ga-PSMA PET and 0.57 (95% CI: 0.43-0.71) for mpMRI, and specificities were both 0.84 (68Ga-PSMA PET 95% CI: 0.75-0.91, mpMRI 95% CI: 0.76-0.91).For SVI, sensitivities were 0.57 (95% CI: 0.46-0.68) for 68Ga-PSMA PET and 0.70 (95% CI: 0.60-0.80) for mpMRI, with specificities of 0.92 (95% CI: 0.86-0.96) for 68Ga-PSMA PET and 0.94 (95% CI: 0.89-0.98) for mpMRI. There were no notable variations in sensitivity or specificity between the two methods for detecting ECE and SVI (P = 0.89 and 0.93 for ECE, 0.09 and 0.57 for SVI).

Conclusions

This meta-analysis indicates that 68Ga-PSMA PET has similar sensitivity and specificity to mpMRI in local prostate cancer staging. Nevertheless, the limited study sample size calls for further, larger prospective studies to validate these findings.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522438, identifier CRD42024522438.
Case report: Patient-derived organoids promoting personalized treatment in invasive urothelial carcinoma
Authors: Liu Xun , Han Xuebing , Wei Shuqing , Zhang Changwen
Published: November 2024

Tumor organoids, an in-vitro three-dimensional model, possess high potential for investigating tumor biology and treatment response and have been demonstrated more appropriate for drug assessment than two-dimensional cultures. Herein, we described two cases of invasive high-grade urothelial carcinoma who underwent radical cystectomy successfully following use of patient-derived organoids (PDOs) for drug screening to inform therapeutic decisions. In these two cases, the PDOs cultured by biopsy tissues were both sensitive to the combination of gemcitabine and cisplatin. After neoadjuvant chemotherapy (NAC) with gemcitabine and cisplatin, the patients responded well, and radical cystectomy was performed successfully. No recurrence or metastasis was observed within 6 months after surgery. This small case series suggests that the patient-derived urothelial carcinoma organoids contribute to optimizing NAC options to guide personalized treatment and improve the survival outcomes.
The role of systemic immune-inflammation index in predicting pathological complete response of breast cancer after neoadjuvant therapy and the establishment of related predictive model
Authors: Zhang Ziyue , Zeng Yixuan , Liu Wenbo
Published: November 2024

Objective

To investigate the role of systemic immune-inflammation index (SII) in complete pathological response (pCR) of breast cancer patients after neoadjuvant chemotherapy, and to establish and validate a nomogram for predicting pCR.

Methods

Breast cancer patients were selected from the First Affiliated Hospital of Xi’an Jiaotong University from January 2020 to December 2023. The optimal cut-off value of SII was calculated via ROC curve. The correlation between SII and clinicopathological characteristics was analyzed by Chi-square test. Logistic regression analysis was performed to evaluate the factors that might affect pCR. Based on the results of Logistic regression analysis, a nomogram for predicting pCR was established and validated.

Results

A total of 112 breast cancer patients were included in this study. 33.04% of the patients achieved pCR after neoadjuvant therapy. Chi-square test showed that SII was significantly correlated with pCR (P=0.001). Logistic regression analysis suggested that Ki-67 (P=0.039), therapy cycle (P<0.001), CEA (P=0.025) and SII (P=0.019) were independent predictors of pCR after neoadjuvant chemotherapy. A nomogram based on Ki-67, therapy cycle, CEA and SII showed a good predictive ability.

Conclusion

Ki-67, therapy cycle, CEA and SII were independent predictors of pCR of breast cancer after neoadjuvant chemotherapy. The nomogram based on the above positive factors showed a good predictive ability.
Thematic trends and knowledge-map of tumor-infiltrating lymphocytes in breast cancer: a scientometric analysis
Authors: Shi Jinan , Pan Lei , Ma Feixia , Zhang Ganlu , Duan Yin
Published: November 2024

Background

Tumor-infiltrating lymphocytes (TILs), essential for the anti-tumor response, are now recognized as promising and cost-effective biomarkers with both prognostic and predictive value. They are crucial in the precision treatment of breast cancer, particularly for predicting clinical outcomes and identifying candidates for immunotherapy. This study aims to encapsulate the current knowledge of TILs in breast cancer research while evaluating research trends both qualitatively and quantitatively.

Methods

Publications on TILs in breast cancer studies from January 1, 2004, to December 31, 2023, were extracted from the Web of Science Core Collection. Co-occurrence and collaboration analyses among countries/regions, institutions, authors, and keywords were performed with Bibliometrix R packages and VOSviewer software. CiteSpace was used for reference and keyword burst detection, while high-frequency keyword layouts were generated using BICOMB. gCLUTO was employed for biclustering analysis of the binary co-keyword matrix.

Results

A total of 2,066 articles on TILs in breast cancer were identified. Between 2004 and 2023, the USA and Milan University led productivity in terms of country/region and institution, respectively. The journals “CANCERS,” “Breast Cancer Research and Treatment,” and “Frontiers in Oncology” published the most articles on this topic. Loi S was the leading author, with the highest number of publications and co-citations. Co-keyword analysis revealed six research hotspots related to TILs in breast cancer. The pathological assessment of TILs using artificial intelligence (AI) remains in its early stages but is a key focus. Burst detection of keywords indicated significant activity in “immune cell infiltration”, “immune checkpoint inhibitors”, and “hormone receptor” over the past three years.

Conclusion

This study reviews recent advancements and trends in TILs research in breast cancer using scientometric analysis. The findings offer valuable insights for funding decisions and developing innovative strategies in TILs research, highlighting current research frontiers and trends.
Association between sarcopenia and outcomes of surgically treated oral squamous cell carcinoma: a systematic review and meta‐analysis
Authors: Luo Kai , Chen Kaiming , Li Yu , Ji Yang
Published: November 2024

Background

Sarcopenia is a significant predictor of perioperative adverse outcomes for a variety of malignancies and has significant negative effects on surgical and oncology outcomes. The development of sarcopenia is mainly attributed to aging, inactivity, poor nutrition, and decreased testosterone levels, which suggest a poor prognosis after surgery. Therefore, the primary objective of this systematic review and meta-analysis was to determine the effect of sarcopenia on postoperative survival in patients with oral squamous cell carcinoma.

Methods

We systematically searched databases including PubMed, Embase, Cochrane Library, Medline and Web of Science from inception to 12 July 2023, to determine the prognostic value of sarcopenia in oral squamous cell carcinoma. The primary outcome was three-year survival, and secondary outcomes were one-year survival, five-year survival, infection and pneumonia within 30 days postoperatively. Original studies comparing postoperative outcomes in patients with sarcopenia and non-sarcopenia for oral squamous cell carcinoma curative therapy were met the eligibility criteria. We used Endnote X9 for the screening process and used RevMan 5.4.1 for our meta-analysis, all results in this study were performed using a random-effects model. QUIPS (Quality in Prognosis Studies) tools and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) were used for risk of bias and quality of evidence assessment.

Result

Ten original studies with 50611 patients met the inclusion criteria. Meta-analysis showed that patients with sarcopenia reduced three-year OS after surgery (OR = 0.73, 95% CI = 0.66-0.81, P < 0.00001). The one-year OS (OR = 0.71, 95% CI = 0.67-0.75, P < 0.00001) and five-year OS (OR = 0.60, 95% CI = 0.45-0.79, P = 0.0003) decreased significantly. Patients with sarcopenia had significantly increased 30-day postoperative mortality and an also increased risk of pneumonia (OR = 1.36, 95% CI = 1.24-1.49, P < 0.00001) and surgical site infection (OR = 2.49, 95% CI = 1.06-5.84, P = 0.04).

Conclusion

Sarcopenia is associated with reduced survival in patients after curative resection. Meanwhile, 30-day mortality, postoperative pneumonia and surgical site infection were significantly higher than those in nonsarcopenic patients. Sarcopenia as an extremely important factor of postoperative adverse outcomes in OSCC patients need special attention.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023444424.