bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1
Authors: Hioe Catarina E. , Liu Xiaomei , Banin Andrew N. , Heindel Daniel W. , Klingler Jéromine , Rao Priyanka G. , Luo Christina C. , Jiang Xunqing , Pandey Shilpi , Ordonez Tracy , Barnette Philip , Totrov Maxim , Zhu Jiang , Nádas Arthur , Zolla-Pazner Susan , Upadhyay Chitra , Shen Xiaoying , Kong Xiang-Peng , Hessell Ann J. 
Published: October 2023

IntroductionNeutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.ObjectiveThis study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).MethodsFour groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro.ResultsRabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses.ConclusionThese data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.
Dynamics and ecological reassembly of the human gut microbiome and the host metabolome in response to prolonged fasting
Authors: Sang Xiaopu , Li Shenghui , Guo Ruochun , Yan Qiulong , Liu Changxi , Zhang Yue , Lv Qingbo , Wu Lili , Ma Jie , You Wei , Feng Ling , Sun Wen 
Published: October 2023

IntroductionProlonged fasting is an intervention approach with potential benefits for individuals with obesity or metabolic disorders. Changes in gut microbiota during and after fasting may also have significant effects on the human body.MethodsHere we conducted a 7-days medically supervised water-only fasting for 46 obese volunteers and characterized their gut microbiota based on whole-metagenome sequencing of feces at five timepoints.ResultsSubstantial changes in the gut microbial diversity and composition were observed during fasting, with rapid restoration after fasting. The ecological pattern of the microbiota was also reassembled during fasting, reflecting the reduced metabolic capacity of diet-derived carbohydrates, while other metabolic abilities such as degradation of glycoproteins, amino acids, lipids, and organic acid metabolism, were enhanced. We identified a group of species that responded significantly to fasting, including 130 fasting-resistant (consisting of a variety of members of Bacteroidetes, Proteobacteria, and Fusobacteria) and 140 fasting-sensitive bacteria (mainly consisting of Firmicutes members). Functional comparison of the fasting-responded bacteria untangled the associations of taxon-specific functions (e.g., pentose phosphate pathway modules, glycosaminoglycan degradation, and folate biosynthesis) with fasting. Furthermore, we found that the serum and urine metabolomes of individuals were also substantially changed across the fasting procedure, and particularly, these changes were largely affected by the fasting-responded bacteria in the gut microbiota.DiscussionOverall, our findings delineated the patterns of gut microbiota alterations under prolonged fasting, which will boost future mechanistic and clinical intervention studies.
The impact of Helicobacter pylori eradication with vonoprazan-amoxicillin dual therapy combined with probiotics on oral microbiota: a randomized double-blind placebo-controlled trial
Authors: Peng Ruolin , Zhang Zhenyu , Qu Yi , Chen Weiwei 
Published: October 2023

BackgroundHelicobacter pylori infection and eradication have been reported to cause dysbiosis of the oral microbiota. Probiotics are increasingly being used to maintain the balance of the oral microbiota. We aimed to investigate the effects of H. pylori infection, H. pylori eradication with vonoprazan-amoxicillin dual therapy, and probiotics supplementation on the oral microbiota.MethodsH. pylori positive patients were randomly assigned to a vonoprazan-amoxicillin regimen plus probiotics (BtT group) or the placebo (PT group) for 14 days. H. pylori negative population served as normal controls. Tongue coating samples were collected from 60 H. pylori positive patients at three time points (before H. pylori eradication, after H. pylori eradication, and at confirmation of H. pylori infection cure) and 20 H. pylori negative subjects. 16S rRNA gene sequencing was used to analyze the oral microbiota.ResultsH. pylori was detected in the oral cavity in positive (34/60), negative (7/20), and eradicated (1/60) subjects using high-throughput sequencing. Compared with normal controls, H. pylori positive patients exhibited higher richness (p = 0.012) and comparable diversity (p = 0.075) of oral microbiota. Beta diversity and KEGG analysis showed oral flora composition and function differences in H. pylori positive and negative subjects. Alpha diversity dramatically decreased after H. pylori eradication and modestly increased with confirmation of H. pylori eradication. Beta diversity and LEfSe analysis revealed distinct structures, and KEGG analysis showed distinct signaling pathways of tongue coating flora at three time points. There was a significant reduction of Firmicutes and Lactobacillus after H. pylori erdication. The PT group and BtT group had identical compositional and functional differences of oral microbiota at three time points.ConclusionNo substantial link existed between oral and stomach H. pylori, while removing gastric H. pylori helped eliminate oral H. pylori. H. pylori infection and vonoprazan-amoxicillin dual therapy affected oral microbiota diversity, structure, and function. H. pylori eradication demonstrated a suppressive impact on the proliferation of oral pathogens, specifically Firmicutes and Lactobacillus. Nevertheless, probiotics supplementation did not reduce the oral microbial disturbance caused by H. pylori eradication.Clinical trial registrationhttps://www.chictr.org.cn/, identifiers CHICTR2200060023.
Prevalence of cerebral palsy comorbidities in China: a systematic review and meta-analysis
Authors: Gong Chao , Liu Xiaopei , Fang Liya , Liu Annan , Lian Beibei , Qi Xunzhong , Chen Shuyue , Li Huiqing , Zhao Ming , Guo Jin , Zhou Shaobo 
Published: October 2023

ObjectivesThis systematic review aimed to comprehensively understand the comorbidity of cerebral palsy (CP) in China.MethodsWe searched through databases in both Chinese and English until December 2022 to gather cross-sectional studies on the comorbidity of CP in China. After two reviewers independently screened the articles, collected the data, and assessed the bias risk, a meta-analysis was conducted using the Stata 17.0 software.ResultsA total of 73 articles were included. Of these, 16 articles reported total comorbidity, with a prevalence of 79.7% (95% CI: 73.8–85.7%); 56 articles reported epilepsy, with a prevalence of 17.9% (95% CI: 15.4–20.4%); 48 articles reported intellectual disability, with a prevalence of 58.0% (95% CI: 51.8–64.3%); 32 articles reported speech disorders, with a prevalence of 48.0% (95% CI: 41.6–54.4%); 41 articles reported hearing disorders, with a prevalence of 17.2% (95% CI: 13.0–21.4%); and 35 articles reported vision disorders, with a prevalence of 23.1% (95% CI: 16.3–29.8%). The topographical type of CP was the primary source of heterogeneity in the prevalence of epilepsy. Diagnostic criteria for CP, clinical type of CP, GMFCS, publishing time, and topographical type of CP were the primary sources of heterogeneity in the prevalence of intellectual disability. Clinical type of CP and topographical type were the primary sources of heterogeneity in the prevalence of speech disorders. Finally, the region was the primary source of heterogeneity in the prevalence of hearing disorders.ConclusionThe prevalence of comorbidities in CP is high in China. Comorbidities are related to the characteristics, severity, and risk factors of brain insult and have a particular relationship with regional economic development and medical and health levels.
Amino acid profiles, disease activity, and protein intake in adult patients with Crohn’s disease
Authors: Cioffi Iolanda , Di Vincenzo Olivia , Imperatore Nicola , Fisco Mariagrazia , Testa Anna , Scialò Filippo , Castiglione Fabiana , Ruoppolo Margherita , Pasanisi Fabrizio , Santarpia Lidia 
Published: October 2023

IntroductionCrohn’s disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with a relapsing–remitting course. Amino acids (AAs) may play critical roles in the intestinal manifestations of disease, due to their involvement in many metabolic and immune functions. The present study aimed to explore serum AA concentrations in adult patients with CD, looking into their variations due to disease activity, surgery and protein content of diet. Eventually, the link between AAs and inflammatory markers was also assessed.MethodsConsecutive adult patients aged 18–65 years with diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record to assess protein intake. Disease activity was clinically defined using the Crohn’s Disease Activity Index (CDAI), while blood samples were taken to analyze serum AA profile and inflammatory markers.ResultsA total of 103 patients with CD (61 men and 42 women; age:39.9 ± 13.9 years, BMI: 23.4 ± 3.51 kg/m2) were included. Tryptophan levels were found to be remarkably decreased in most subjects, unrelated to disease activity. On the contrary, concentration of lysine, leucine, valine and glutamine decreased in active versus quiescent CD patients, while aspartic acid, glutamate and glycine increased. The latter AAs were also directly correlated with CDAI and serum interleukin (IL)- 1β concentration. Considering the total protein intake, expressed as g/kg/body weight, we observed a reduction in some essential AAs in patients with unmet protein requirements compared to patients who met the recommendation.DiscussionIn conclusion, specific AAs varied according to disease activity and protein intake, adjusted to body weight and disease status. Glu and Asp concentrations raised with increasing IL-1β. However, extensive research is needed to understand the mechanisms underpinning the link between variation in serum AAs, disease activity and protein intake in patients with CD.
Prognostic significance of the pretreatment pan-immune-inflammation value in cancer patients: an updated meta-analysis of 30 studies
Authors: Hai-Jing Yu , Shan Ren , Jie-Qiong Xia 
Published: October 2023

BackgroundThe pan-immune-inflammation value (PIV) has been reported as a promising prognostic biomarker in multiple cancers but still remains inconclusive. The objective of this study is to systematically investigate the association of the pretreatment PIV with survival outcomes in cancer patients, based on available literature.MethodsOnline databases including PubMed, Embase and the Web of Science were thoroughly searched for studies evaluating the prognostic role of the pretreatment PIV in cancers from the inception to June 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were always assessed using a random-effects model. Statistical analyses were performed using Stata 12.0.ResultsThirty studies were finally included after comprehensively study searching. In total, 8,799 cancer patients were enrolled in this meta-analysis. The pooled results demonstrated that patients in the high PIV group had a significantly poorer overall survival (HR = 2.07; 95%CI: 1.77–2.41; I2 = 73.0%) and progression-free survival (HR = 1.83; 95%CI: 1.37–2.45; I2 = 98.2%) than patients in the low PIV group. The prognostic significance of the PIV score on overall survival and progression-free survival was observed across various geographical regions, tumor stages and treatment strategies. Sensitivity analyses supported the stability of the above combined results.ConclusionThis meta-analysis demonstrated that the pretreatment PIV could be a non-invasive and efficacious prognostic biomarker for cancer patients.
Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac
Authors: Eijkelenkamp Hidde , Grimbergen Guus , Daamen Lois A. , Heerkens Hanne D. , van de Ven Saskia , Mook Stella , Meijer Gert J. , Molenaar Izaak Q. , van Santvoort Hjalmar C. , Paulson Eric , Erickson Beth Ann , Verkooijen Helena M. , Hall William Adrian , Intven Martijn P. W. 
Published: October 2023

IntroductionOnline adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT.MethodsWe evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3–12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan–Meier analysis to calculate the cumulative overall survival.ResultsA total of 80 patients were assessed with a median FU of 8 months (range 1–39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3–4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3–4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%.ConclusionOnline adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3–4 toxicity and a stable QoL at 3 months of FU.
Efficacy and safety of cryoablation for localized renal tumor as an alternative approach to partial nephrectomy
Authors: Barjolle Irène , Ah-Thiane Loic , Frampas Eric , Karam Georges , Rigaud Jérôme , David Arthur 
Published: October 2023

IntroductionRenal cryoablation displays a profile of high tolerance, including in a frail population. Cryoablation appears as a validated alternative treatment to surgery for renal tumors smaller than 4 cm. However, evidence is lacking for larger tumors, despite encouraging data for tumors up to 7 cm.Material and methodsThis retrospective descriptive study of a population with a stage T1b renal tumor treated by cryoablation was conducted at the Nantes University Hospital between January 2009 and July 2021. Primary endpoint was 3-year rate of local recurrence. Secondary endpoints included technical efficacy, overall and cancer-specific survivals, and safety assessment.ResultsA total of 63 patients were analyzed. Three-year rate of local recurrence was 11.1%. Primary and secondary technical efficacies were achieved in 88.9% and 96.8% of patients, respectively, and 3-year overall and cancer-specific survival were 87.3% and 95.2%, respectively. Most patients (73%) experienced no complications, 13% of patients had minor (CIRSE grades 1 or 2) adverse effects, and 13% had severe but non-lethal (CIRSE grade 3) adverse effects. One patient died following cryoablation due to colic perforation. The most common AE (all grades) was hemorrhage (9.5%).DiscussionThis study showed a good efficacy and safety of cryoablation for renal tumors up to 7 cm (T1b). Our results were consistent with a rather sparse literature and contributed to guide future recommendations about cryoablation as an alternative to surgery for T1b renal tumors.
Primary presentation and clinical course of pediatric and adolescent patients with differentiated thyroid carcinoma after radioiodine therapy
Authors: Burgard Caroline , Zacherl Mathias Johannes , Todica Andrei , Hornung Julia , Grawe Freba , Pekrul Isabell , Zimmermann Petra , Schmid-Tannwald Christine , Ladurner Roland , Krenz Detlef , Trupka Arnold , Wagner Johanna , Bartenstein Peter , Spitzweg Christine , Wenter Vera 
Published: October 2023

IntroductionDifferentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients.MethodsEighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up.ResultsPrepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period.ConclusionPrepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.
The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling
Authors: Li Song , Chen Dianze , Guo Huiqin , Liu Dandan , Yang Chunmei , Zhang Ruliang , Wang Tianxiang , Zhang Fan , Bai Xing , Yang Yanan , Sun Nana , Zhang Wei , Zhang Li , Zhao Gui , Peng Liang , Tu Xiaoping , Tian Wenzhi 
Published: October 2023

BackgroundA significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC.MethodsIMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys.ResultsIn vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt’s lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile.ConclusionIMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.