bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal Microbiome Associated With Immune-Related Adverse Events for Patients Treated With Anti-PD-1 Inhibitors, a Real-World Study
Authors: Liu Wenhui , Ma Fang , Sun Bao , Liu Yiping , Tang Haoneng , Luo Jianquan , Chen Huiqing , Luo Zhiying 
Published: December 2021

AimImmune checkpoint inhibitors (ICIs) have updated the treatment landscape for patients with advanced malignancies, while their clinical prospect was hindered by severe immune-related adverse events (irAEs). The aim of this study was to research the association between gut microbiome diversity and the occurrence of ICI-induced irAEs.Patients and MethodWe prospectively obtained the baseline fecal samples and clinical data from patients treated with anti-PD-1 inhibitors as monotherapy or in combination with chemotherapy or antiangiogenesis regardless of treatment lines. The 16S rRNA V3-V4 sequencing was used to test the gene amplicons of fecal samples. The development of irAEs was evaluated and monitored from the beginning of therapy based on CTCAE V5.01.ResultsA total of 150 patients were included in the study and followed up for at least 6 months. A total of 90 (60%) patients developed at least one type of adverse effect, among which mild irAEs (grades 1–2) occurred in 65 patients (72.22%) and severe irAEs (grades 3–5) in 25 patients (27.78%). Patients with severe irAEs showed a visible higher abundance of Streptococcus, Paecalibacterium, and Stenotrophomonas, and patients with mild irAEs had a higher abundance of Faecalibacterium and unidentified_Lachnospiraceae. With the aid of a classification model constructed with 5 microbial biomarkers, patients without irAEs were successfully distinguished from those with severe irAEs (AUC value was 0.66).ConclusionCertain intestinal bacteria can effectively distinguish patients without irAEs from patients with severe irAEs and provide evidence of gut microbiota as an informative source for developing predictive biomarkers to predict the occurrence of irAEs.
Soluble Receptor Isoform of IFN-Beta (sIFNAR2) in Multiple Sclerosis Patients and Their Association With the Clinical Response to IFN-Beta Treatment
Authors: Aliaga-Gaspar Pablo , Hurtado-Guerrero Isaac , Ciano-Petersen Nicolas Lundahl , Urbaneja Patricia , Brichette-Mieg Isabel , Reyes Virginia , Rodriguez-Bada Jose Luis , Alvarez-Lafuente Roberto , Arroyo Rafael , Quintana Ester , Ramió-Torrentà Lluis , Alonso Ana , Leyva Laura , Fernández Oscar , Oliver-Martos Begoña 
Published: December 2021

PurposeInterferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-β. However, its role regarding the clinical response to IFN-β for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the in vitro short-term effects and after 6 and 12 months of IFN-β therapy on sIFNAR2 production and their association with the clinical response in MS patients.MethodsNinety-four RRMS patients were included and evaluated at baseline, 6 and 12 months from treatment onset. A subset of 41 patients were classified as responders and non-responders to IFN-β therapy. sIFNAR2 serum levels were measured by ELISA. mRNA expression for IFNAR1, IFNAR2 splice variants, MxA and proteases were assessed by RT-PCR. The short-term effect was evaluated in PBMC from RRMS patients after IFN-β stimulation in vitro.ResultsProtein and mRNA levels of sIFNAR2 increased after IFN-β treatment. According to the clinical response, only non-responders increased sIFNAR2 significantly at both protein and mRNA levels. sIFNAR2 gene expression correlated with the transmembrane isoform expression and was 2.3-fold higher. While MxA gene expression increased significantly after treatment, IFNAR1 and IFNAR2 only slightly increased. After short-term IFN-β in vitro induction of PBMC, 6/7 patients increased the sIFNAR2 expression.ConclusionsIFN-β administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-β therapy.
Active or Autoclaved Akkermansia muciniphila Relieves TNF-α-Induced Inflammation in Intestinal Epithelial Cells Through Distinct Pathways
Authors: Luo Yuheng , Lan Cong , Xie Kunhong , Li Hua , Devillard Estelle , He Jun , Liu Li , Cai Jingyi , Tian Gang , Wu Aimin , Ren Zhihua , Chen Daiwen , Yu Bing , Huang Zhiqing , Zheng Ping , Mao Xiangbing , Yu Jie , Luo Junqiu , Yan Hui , Wang Quyuan , Wang Huifen , Tang Jiayong 
Published: December 2021

Intestinal inflammation is a major threat to the health and growth of young animals such as piglets. As a next-generation probiotics, limited studies have shown that Akkermansia muciniphila could alleviate inflammation of intestinal epithelial cells (IECs). In this study, a TNF-α-induced inflammatory model of IPEC-J2 cells, the intestinal porcine enterocytes, was built to evaluate the effects of active or inactive A. muciniphila on the inflammation of IECs. The viability of IPEC-J2 cells was the highest when treated with active (108 copies/mL) or inactive (109 copies/mL) A. muciniphila for 7.5 h (P &lt; 0.01). Treated with 20 ng/mL of TNF-α and followed by a treatment of A. muciniphila, the mRNA level of proinflammatory cytokines (IL-8, IL-1β, IL-6 and TNF-α) was remarkably reduced (P &lt; 0.05) along with the increased mRNA level of tight junction proteins (ZO-1 and Occludin, P &lt; 0.05). Flow cytometry analysis showed that active or inactive A. muciniphila significantly suppressed the rate of the early and total apoptotic of the inflammatory IPEC-J2 cells (P &lt; 0.05). According to results of transcriptome sequencing, active and inactive A. muciniphila may decline cell apoptosis by down-regulating the expression of key genes in calcium signaling pathway, or up-regulating the expression of key genes in cell cycle signaling pathway. And the bacterium may alleviate the inflammation of IECs by down-regulating the expression of PI3K upstream receptor genes. Our results indicate that A. muciniphila may be a promising NGP targeting intestinal inflammation.
Interaction Between Arousals and Ventilation During Cheyne-Stokes Respiration in Heart Failure Patients: Insights From Breath-by-Breath Analysis
Authors: Pinna Gian Domenico , Robbi Elena , Bruschi Claudio , La Rovere Maria Teresa , Maestri Roberto 
Published: December 2021

Study Objectives: Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause ventilatory overshoot and a consequent longer apnea, thereby sustaining and exacerbating ventilatory instability. However, data supporting this model are lacking. We investigated the relationship between arousals, hyperpnea and post-hyperpnea apnea length during CSR-CSA.Methods: Breath-by-breath changes in ventilation associated with the occurrence of arousal were evaluated in 18 heart failure patients with CSR-CSA, apnea-hypopnea index ≥15/h and central apnea index ≥5/h. The change in apnea length associated with the presence of arousal during the previous hyperpnea was also evaluated. Potential confounding variables (chemical drive, sleep stage) were controlled for.Results: Arousals were associated with a large increase in ventilation at the beginning of the hyperpnea (+76 ± 35%, p &lt; 0.0001), that rapidly declined during its crescendo phase. Around peak hyperpnea, the change in ventilation was −8 ± 26% (p = 0.14). The presence of arousal during the hyperpnea was associated with a median increase in the length of the subsequent apnea of +4.6% (Q1, Q2: −0.7%, 20.5%; range: −8.5%, 36.2%) (p = 0.021). The incidence of arousals occurring at the beginning of hyperpnea and mean ventilation in the region around its peak were independent predictors of the change in apnea length (p = 0.004 and p = 0.015, respectively; R2 = 0.78).Conclusions: Arousals from sleep during CSR-CSA in heart failure patients are associated with a rapidly decreasing ventilatory overshoot at the beginning of the hyperpnea, followed by a tendency toward a slight ventilatory undershoot around its peak. On average, arousals are also associated with a modest increase in post-hyperpnea apnea length; however, large increases in apnea length (&gt;20%) occur in about a quarter of the patients.
Sonographic Tophi and Inflammation Are Associated With Carotid Atheroma Plaques in Gout
Authors: Calabuig Irene , Martínez-Sanchis Agustín , Andrés Mariano 
Published: December 2021

Objective: Gout and cardiovascular disease are closely related, but the mechanism connecting them remains unknown. This study aims to explore whether urate crystal deposits and inflammation (assessed by ultrasound) are associated with carotid atherosclerosis.Methods: We included consecutive patients with crystal-proven gout newly presenting to a tertiary rheumatology unit. Patients under urate-lowering treatment were excluded. Ultrasound assessment was performed during intercritical periods. Musculoskeletal scans evaluated six joints and four tendons for urate crystal deposits (double contour, aggregates, and tophi), and power Doppler (PD) signal (graded 0–3) as a marker of local inflammation. The sum of locations showing deposits or a positive PD signal (≥1) was registered. Carotids were scanned for increased intima-media thickness (IMT) and atheroma plaques, according to the Mannheim consensus. Associations were analyzed using logistic regression.Results: The study included 103 patients showing sonographic crystal deposits at the examined locations (mean sum 9.9, minimum 2); tophi were the most frequent. Two-thirds of participants presented a positive PD signal (30.1% grade 2–3). In the carotid scans, 59.2% of participants showed atheroma plaques, and 33.0% increased IMT. Tophi (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03–1.50) and a positive PD signal (OR 1.67; 95% CI 1.09–2.56) were significantly associated with atheroma plaques, while an increased IMT showed no sonographic association.Conclusion: Sonographic crystal deposits and subclinical inflammation were consistently observed in patients with intercritical gout. Tophi and a positive PD signal were linked to carotid atherosclerosis. Our findings may contribute to understanding the complex relationship between gout and atherosclerosis.
Follow-Up of Blood Pressure, Arterial Stiffness, and GFR in Pediatric Kidney Transplant Recipients
Authors: Végh Anna , Bárczi Adrienn , Cseprekál Orsolya , Kis Éva , Kelen Kata , Török Szilárd , Szabó Attila J. , Reusz György S. 
Published: December 2021

Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function.Patients and Methods: 52 RTx patients (22 males) were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0–4.7] (T1) and 9.3[6.3–11.8] years (T2) after transplantation (median [range]).Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2.Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR.
Krabbe Disease Associated With Mitochondrial Dysfunction in a Chinese Family
Authors: Wu Liwen , Liao Xiangfu , Yang Sai , Gan Siyi 
Published: December 2021

Background: Krabbe disease is caused by biallelic mutations of GALC gene. NDUFAF1 gene mutations are related to mitochondrial encephalopathy. To date, there has been no report on the co-pathogenesis of these two gene mutations. There were three children in a family who presented with global developmental retardation. MRI showed lesions in the white matter and dentate nucleus of the cerebellum.Methods: Clinical data of the proband and her family members were gathered in a retrospective manner. Karyotype, FISH, whole exome sequencing was performed using genomic DNAs extracted from peripheral blood samples. Enzyme activities of galactosylceramidase (GALC) and mitochondria were determined to verify gene functions.Results: This study reported a pedigree of leukoencephalopathy, in which 3 of the 4 children showed phenotypes of developmental delay, hearing/visual impairment, and peripheral neuropathy. Mutations of NDUFAF1 (c.278A&gt;G; p. His93Arg, c.247G&gt; A; p. Asp83Asn) and GALC (c.599C&gt;A; p.Ser200*) were identified in all three cases. The proband's parents carried these mutations as a heterozygous state. Clinical features, MRI changes, enzyme activity of GALC, and mitochondrial function analysis demonstrated that this pedigree was caused by GALC and NDUFAF1 gene mutations working together.Conclusion: We first report a pedigree of Krabbe disease with biallelic mitochondrial gene NDUFAF1 mutations. For multiple gene mutations found in genetic testing, clinical phenotypes, gene functions, and family history should be comprehensively analyzed. Gene panel examination may miss pathogenic mutations, and prenatal diagnosis of patients with polygenic inheritance needs careful consideration.
Intraoperative Radiotherapy Is Not a Better Alternative to Whole Breast Radiotherapy as a Therapeutic Option for Early-Stage Breast Cancer
Authors: Wang Linwei , Sun Min , Yang Shuailong , Chen Yuanyuan , Li Tian 
Published: December 2021

ObjectiveIntraoperative radiotherapy (IORT) in early-stage breast cancer has been studied over the years. However, it has not been demonstrated whether IORT is more suitable as a therapeutic option for early-stage breast cancer than whole breast radiotherapy (WBRT). Therefore, we performed a meta-analysis to compare the efficacy and safety of IORT to those of WBRT as therapeutic options for early-stage breast cancer patients receiving breast-conserving surgery (INPLASY2020120008).MethodsPubMed, Embase, and Cochrane Library databases were searched from inception to October 2021. Computerized and manual searches were adopted to identify eligible randomized control trials from online databases. Risk ratio (RR) and 95% confidence intervals (CI) were calculated by random-effect models to assess the relative risk. Potential publication bias was quantified by Begg’s and Egger’s tests.ResultsBased on our inclusion criteria, 10 randomized control trials involving 5,698 patients were included in this meta-analysis. This meta-analysis showed that the IORT group was associated with a higher local recurrence risk (RR = 2.111, 95% CI, 1.130–3.943, p = 0.0191), especially in the long-term follow-up subgroup or published after 2020 subgroup or Caucasian subgroup (RR = 2.404, 95% CI, 1.183–4.885, p = 0.0154). Subgroup analysis showed that the IORT group had a higher recurrence risk than the WBRT group in the polycentric randomized controlled trial subgroup (RR = 1.213, 95% CI, 1.030–1.428, p = 0.0204). Pooled analysis showed that there was no statistically significant difference in overall survival, recurrence-free survival, distant metastasis-free survival, and cancer-specific survival between IORT and WBRT groups. Additionally, the risk of skin toxicity was reduced, but the incidences of fat toxicity, edema, and scar calcification were significantly increased in the patients who underwent IORT in comparison to those who underwent WBRT.ConclusionThis meta-analysis revealed that IORT was not a better alternative to WBRT. More large-scale and well-designed clinical trials with longer follow-up periods are encouraged to further investigate the value of IORT.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-12-0008/.
Cariprazine Use in Early Psychosis: Three Case Reports
Authors: Coentre Ricardo , Saraiva Rodrigo , Sereijo Carolina , Levy Pedro 
Published: December 2021

Objective: Cariprazine is a new atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia (1, 2) and for the treatment of manic or mixed episodes associated with bipolar I disorder (1). Recently, cariprazine also got extended FDA-approval for the treatment of depressive episodes in adults with bipolar I disorder (3). The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis. For its particular performance and tolerability, cariprazine is becoming an important option for the treatment of first-episode psychosis.Method: Three patients experiencing first-episode psychosis (FEP) were successfully treated with cariprazine. Two patients were in their first months of the disease, and the third patient was in his third year after the FEP.Results: The three patients had a diagnosis of non-affective FEP, which includes schizophrenia, delusional disorder, and schizoaffective disorder. One of them was in their third year after the FEP with a predominance of negative symptoms at this stage of the disorder. All the patients were treated with cariprazine with a target dose of 3–4.5 mg/day. The three patients showed improvements in their psychosis, including a decrease in negative symptoms. No significant side effects were reported.Conclusion: Our three case reports indicate that cariprazine is an atypical antipsychotic beneficial in the treatment of early psychosis. Treatment with low doses of cariprazine could be effective and tolerable in this phase of the disorder. Future studies with longer follow-up of FEP patients are recommended to confirm these positive results of cariprazine in the early phases of psychosis.
Men’s Attitude Towards Contraception and Sexuality, Women’s Empowerment, and Demand Satisfied for Family Planning in India
Authors: Mejía-Guevara Iván , Cislaghi Beniamino , Darmstadt Gary L. 
Published: December 2021

Whilst the prevalence of unmet need and contraceptive use remained unchanged for 10 years (between 2005–2015) in India, gender restrictive norms and power imbalances also have persisted, preventing married women from meeting their family planning desires. Data for this study are from the 2015–6 National Family Household Survey, which contains information on fertility preferences and family planning for women in reproductive age. As a proxy for men’s attitudinal norms, we aggregated men’s perceptions regarding contraception (contraception is women’s business, women who use contraception may become promiscuous) and control over their wife (if his wife refuses to have sex, men have the right to deny financial support, have sex with another woman, or beat wife) at district level. Using a three-level random intercepts model, we assessed individual and contextual-level associations of men’s attitudinal norms and met need for contraception among sexually active women (aged 15–49) with any demand for family planning, while adjusting for women’s empowerment indicators [education, job status, and adult marriage] and individual demographic factors. Our results indicate that men’s attitudinal norms are negatively associated with women’s contraceptive use; for instance, a 1 standard deviation increase in the proportion of men who believe that contraception is women’s business was associated with a 12% reduced likelihood of contraceptive use (OR = 0.88, 95% CI 0.82–0.95). Similar associations remained or were stronger after considering only modern methods, or when excluding female sterilization. Furthermore, our contextual effects analysis revealed that women’s higher education or wealth did not improve contraceptive uptake in communities with strong attitudinal norms, but working women or women married as children were more likely to use contraception in those communities. Our results suggest that men’s attitudinal norms may be dominating over women’s empowerment regarding family planning choices among reproductive age women. However, employment appeared to play a strong protective role associated with women’s contraceptive use. It is important for programs seeking to transform gender equality and empower women in making contraceptive choices to consider women’s employment opportunities and to also address male attitudinal norms in the context of the ecosystem in which men and women coexist and interact.
RETRACTED: Smartphone Interventions Effect in Pediatric Subjects on the Day of Surgery: A Meta-Analysis
Authors: Li Li , Ma Jianping , Ma Dan , Zhou Xiaokang 
Published: December 2021

Background: A meta-analysis was performed to evaluate the effect of smartphone interventions on the anxiety of the pediatric subjects at induction on the day of surgery compared to oral midazolam or standard care as control.Methods: A systematic literature search up to June 2021 was performed and nine studies selected 785 pediatric subjects on the day of surgery at the start of the study; 390 of them were using smartphone interventions, 192 were control, and 203 were using oral midazolam. They were reporting relationships between the effects of smartphone interventions on the anxiety of the pediatric subjects at induction on the day of surgery compared to oral midazolam or control. The mean difference (MD) with its 95% CIs was calculated to assess the effect of smartphone interventions on the anxiety of the pediatric subjects at induction on the day of surgery compared to oral midazolam or control using the continuous method with a fixed or a random-effects model.Results: Smartphone interventions in pediatric subjects were significantly related to lower anxiety at induction on the day of surgery (MD, −19.74; 95% CI, −29.87 to −9.61, p &lt; 0.001) compared to control and significantly related to lower anxiety at induction on the day of surgery (MD, −7.81; 95% CI, −14.49 to −1.14, p = 0.02) compared to oral midazolam.Conclusion: Smartphone interventions in pediatric subjects on the day of surgery may have lower anxiety at induction compared to control and oral midazolam. Further studies are needed to confirm these findings.