bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient
Authors: Gao Shan-Yu , Liu Yu-Xing , Dong Yi , Fan Liang-Liang , Ding Qi , Liu Lv 
Published: October 2023

Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear.Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family.Results: A novel splice-altering variant (c.712–2A&gt;G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant.Conclusion: A novel heterozygous splice-altering variant (c.712–2A&gt;G) in the WASHC5 gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.
Human CD79b+ neutrophils in the blood are associated with early-stage melanoma
Authors: Meyer Melissa A. , Dinh Huy Q. , Alimadadi Ahmad , Araujo Daniel J. , Chatterjee Nandini , Gutierrez Norma A. , Zhu Yanfang Peipei , Hunter Emma L. , Liang Shu , Seumois Gregory , Kiosses William B. , Catz Sergio D. , Vijayanand Pandurangan , Ottensmeier Christian , Hedrick Catherine C. 
Published: October 2023

PurposeDue to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage.Experimental designUsing mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning.ResultsWe identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis.ConclusionOur work suggests that CD79b+ neutrophils are associated with early-stage melanoma.
Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study)
Authors: Chen Yizhang , Zhang Jiaguang , Han Gaohua , Tang Jie , Guo Fen , Li Wei , Xie Li , Xu Hao , Zhang Xinyi , Tian Yitong , Pan Lanlan , Shu Yongqian , Ma Ling , Chen Xiaofeng 
Published: October 2023

BackgroundThe efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA.Methods/DesignThis study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator’s choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence.DiscussionWe expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients.Trial registrationhttps://www.clinicaltrials.gov, identifier NCT05494060.
Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease
Authors: Teramoto Yoshiki , Akagawa Shohei , Hori Shin-ichiro , Tsuji Shoji , Higasa Koichiro , Kaneko Kazunari 
Published: October 2023

IntroductionGut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. MethodsFecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.ResultsFor alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusionRuminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD.
Early detection of deterioration in COVID-19 patients by continuous ward respiratory rate monitoring: a pilot prospective cohort study
Authors: Rivas Eva , López-Baamonde Manuel , Sanahuja Josep , Del Rio Elena , Ramis Tomeu , Recasens Anna , López Antonio , Arias Marilyn , Kampakis Stylianos , Lauteslager Timo , Awara Osama , Mascha Edward J. , Soriano Alex , Badía Joan Ramon , Castro Pedro , Sessler Daniel I. 
Published: October 2023

BackgroundTachypnea is among the earliest signs of pulmonary decompensation. Contactless continuous respiratory rate monitoring might be useful in isolated COVID-19 patients admitted in wards. We therefore aimed to determine whether continuous monitoring of respiratory patterns in hospitalized patients with COVID-19 predicts subsequent need for increased respiratory support.MethodsSingle-center pilot prospective cohort study in COVID-19 patients who were cared for in routine wards. COVID-19 patients who had at least one escalation of pulmonary management were matched to three non-escalated patients. Contactless respiratory monitoring was instituted after patients enrolled, and continued for 15 days unless hospital discharge, initiation of invasive mechanical ventilation, or death occurred. Clinicians were blinded to respiratory rate data from the continuous monitor. The exposures were respiratory features over rolling periods of 30 min, 24 h, and 72 h before respiratory care escalation. The primary outcome was a subsequent escalation in ventilatory support beyond a Venturi mask.ResultsAmong 125 included patients, 13 exhibited at least one escalation and were each matched to three non-escalated patients. A total of 28 escalation events were matched to 84 non-escalation episodes. The 30-min mean respiratory rate in escalated patients was 23 breaths per minute (bpm) ranging from 13 to 40 bpm, similar to the 22 bpm in non-escalated patients, although with less variability (range 14 to 31 bpm). However, higher respiratory rate variability, especially skewness over 1 day, was associated with higher incidence of escalation events. Our overall model, based on continuous data, had a moderate accuracy with an AUC 0.81 (95%CI: 0.73, 0.88) and a good specificity 0.93 (95%CI: 0.87, 0.99).ConclusionOur pilot observational study suggests that respiratory rate variability as detected with continuous monitoring is associated with subsequent care escalation during the following 24 h. Continuous respiratory monitoring thus appears to be a valuable increment over intermittent monitoring.Strengths and limitationsOur study was the initial evaluation of Circadia contactless respiratory monitoring in COVID-19 patients who are at special risk of pulmonary deterioration. The major limitation is that the analysis was largely post hoc and thus needs to be confirmed in an out-of-sample population.
Genetic causal relationship between gut microbiome and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study
Authors: Qian Xinyu , Fu Zhida , Diao Chaoyue , Zhang Wenbo , Tao Weiyu , Hu Jiaqi , Zhang Shuqing , Zhao Dongbao 
Published: October 2023

BackgroundSeveral observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.MethodsIn this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.ResultsIVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643–0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008–1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075–1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059–1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.ConclusionThis study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.
Change in sensory integration and regularity of postural sway with the suspensory strategy during static standing balance
Authors: Jiang Linjing , Kasahara Satoshi , Ishida Tomoya , Koshino Yuta , Chiba Ami , Yoshimi Kazumasa , Wei Yuting , Samukawa Mina , Tohyama Harukazu 
Published: October 2023

Background and aimThe suspensory strategy, a method for controlling postural balance in the vertical direction of the center of mass (COM), is considered by the elderly as a means of balance control. The vertical COM control might alter the sensory integration and regularity of postural sway, which in turn impacts balance. However, to date, this was not confirmed. Thus, this study aimed at investigating the influence of the suspensory strategy achieved through knee flexion on the static standing balance.MethodsNineteen participants were monitored at knee flexion angles of 0°, 15°, and 65°. Time-frequency analysis and sample entropy were employed to analyze the COM data. Time-frequency analysis was utilized to assess the energy content across various frequency bands and corresponding percentage of energy within each frequency band. The outcomes of time-frequency are hypothesized to reflect the balance-related sensory input and sensory weights. Sample entropy was applied to evaluate the regularity of the COM displacement patterns.ResultsKnee flexion led to a decreased COM height. The highest energy content was observed at 65° knee flexion, in contrast with the lowest energy observed at 0° in both the anterior–posterior (AP) and medial-lateral (ML) directions. Additionally, the ultra-low-frequency band was more pronounced at 65° than that at 0° or 15° in the ML direction. Furthermore, the COM amplitudes were notably higher at 65° than those at 0° and 15° in the AP and ML directions, respectively. The sample entropy values were lower at 65° and 15° than those at 0° in the ML direction, with the lowest value observed at 65° in the vertical direction.ConclusionThe suspensory strategy could enhance the sensory input and cause sensory reweighting, culminating in a more regular balance control. Such suspensory strategy-induced postural control modifications may potentially provide balance benefits for people with declining balance-related sensory, central processing, and musculoskeletal system functions.
Fructose intake and its association with relative telomere length: an exploratory study among healthy Lebanese adults
Authors: Messerlian Nairie , Zgheib Nathalie , Chokor Fatima Al Zahraa , Nasrallah Mona , Tamim Hani , Nasreddine Lara 
Published: October 2023

IntroductionShorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length.MethodsFollowing a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated.ResultsMean intakes of added and natural fructose were of 39.03 ± 34.12 and 12.28 ± 8.59 g/day, respectively, representing 4.80 ± 3.56 and 1.78 ± 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 ± 35.55 g/day, contributing 6.58 ± 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG).ConclusionIn conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings.
Are there differences between Mediterranean diet and the consumption of harmful substances on quality of life?—an explanatory model in secondary education regarding gender
Authors: Melguizo-Ibáñez Eduardo , Zurita-Ortega Félix , Ubago-Jiménez José Luis , Badicu Georgian , Yagin Fatma Hilal , González-Valero Gabriel , Ardigò Luca Paolo , Puertas-Molero Pilar 
Published: October 2023

BackgroundAdolescence is a key life stage in human development. It is during this stage of development that healthy and physical behaviors are acquired that will last into adulthood. Gender differences in the acquisition of these behaviors have been observed. This research aims to (a) study the levels of Mediterranean diet adherence, quality of life and alcohol and tobacco consumption as regarding the gender of the participants and (b) study the effects of the variable adherence to the Mediterranean diet, alcohol consumption and tobacco consumption on quality of life as a function of the gender of the participants.MethodsA non-experimental, cross-sectional, exploratory study was carried out in a sample of 1,057 Spanish adolescents (Average Age = 14.19; Standard Deviation = 2.87).ResultsThe comparative analysis shows that the male teenagers shows a higher Mediterranean diet adherence compared to the male adolescents (p ≤ 0.05) and a higher consumption of alcoholic beverages (p ≤ 0.05). On the contrary, adolescent girls show a higher consumption of alcoholic beverages than male participants (p ≤ 0.05). The exploratory analysis indicates that for boys, alcohol consumption has a beneficial effect on the quality of life of adolescents (β = 0.904; p ≤ 0.001).ConclusionIn this case, participants show differences in the levels of Mediterranean diet adherence, consumption of harmful substances and quality of life according to gender. Likewise, there are different effects between the variables according to gender. Therefore, gender is a key factor to consider during adolescence.
The efficacy and safety of 5-fluorouracil/cisplatin/vincristine as a multi-agent chemotherapy regimen in gestational trophoblastic neoplasia
Authors: Wang Lu , Wang Qian , Xu Zhen , Yang Linli , Wang Wuliang 
Published: October 2023

ObjectiveTo determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN).MethodsWe performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU. The clinical characteristics, adverse events, and response rates were compared between the groups.ResultsThe patients in the FPV and FAV groups received a total of 228 and 190 courses of chemotherapy, respectively. Complete response (CR) was found in 88.89% (48/54) and 90.48% (38/42) of patients in the FPV group and FAV group, respectively (p = 0.801). Both chemotherapy regimens yielded CR in all low-risk patients (100% vs. 100%), whereas 86.67% and 88.24% of high-risk patients achieved CR (FPV vs. FAV, p = 0.836), respectively. The most common adverse events (AEs) were myelosuppression and gastrointestinal reactions including neutropenia (83.97%), anemia (60.05%), and nausea (46.41%). In comparison to those in the FAV group, patients in the FPV group reported higher rates of grade 1/2 nausea (53.51% vs. 37.89%, p = 0.001), hepatotoxicity (28.95% vs. 17.89%, p = 0.008), oral mucositis (23.25% vs. 10.53%, p = 0.001), and grade 3/4 neutropenia (47.37% vs. 27.37%, p &lt; 0.001), while grade 1/2 diarrhea (7.46% vs. 13.68%, p = 0.037) and grade 3/4 oral mucositis (0 vs. 6.32%, p &lt; 0.001) were much more common in the FAV group. The rate of overall survival at 5 years was 96.8% in the FPV group and 97.3% in the FAV group (p = 0.760), whereas the 5-year disease-free survival rates were 95.9% and 93.9% (p = 0.754), respectively.ConclusionThe FPV and FAV regimens with pulsed intravenous 5-FU yielded comparable CR rates and tolerability in patients with GTN with FIGO scores of &gt;5. Further randomized controlled trials are warranted to validate their efficacy.