bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of drug efficacy by M6A modification patterns in rheumatoid arthritis patients
Authors: Song Shan , Zhao Rong , Qiao Jun , Liu Jia , Cheng Ting , Zhang Sheng-Xiao , Li Xiao-Feng 
Published: August 2022

BackgroundRheumatoid arthritis is a highly heterogeneous autoimmune disease characterized by unpredictable disease flares and significant differences in therapeutic response to available treatments. One possible reason for poor efficacy is that it cannot be treated accurately due to no optimal stratification for RA patients.ObjectiveThis study aims to construct an RA classification model by m6A characters and further predict response to medication.MethodsTwenty m6A regulators were used to construct a random forest diagnosis model, and RNA-seq analysis was employed for external validation. The RNA modification patterns mediated by 20 m6A regulators were systematically evaluated in 1191 RA samples and explored different molecular clusters associated with other immune microenvironment characteristics and biological pathways. Then, we established an m6A score model to quantify the m6A modification patterns. The model was applied to patients at baseline to test the association between m6Ascore and infliximab responsiveness.ResultsThe m6A diagnosis model showed good discriminatory ability in distinguishing RA. Patients with RA were classified into three clusters with distinct molecular and cellular signatures. Cluster A displayed strongly activated inflammatory cells and pathways. Specific innate lymphocytes occupied cluster B. Cluster C was mainly enriched in prominent adaptive lymphocytes and NK-mediated cytotoxicity signatures with the highest m6A score. Patients with a low m6Ascore exhibited significantly infliximab therapeutic benefits compared with those with a high m6Ascore (p&lt; 0.05).ConclusionOur study is the first to provide a comprehensive analysis of m6A modifications in RA, which provides an innovative patient stratification framework and potentially enables improved therapeutic decisions.
Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis
Authors: Therien Aaron D. , Beasley Georgia M. , Rhodin Kristen E. , Farrow Norma E. , Tyler Douglas S. , Boczkowski David , Al-Rohil Rami N. , Holl Eda K. , Nair Smita K. 
Published: August 2022

IntroductionB cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients.MethodsFlow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs.ResultsB cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival.ConclusionThese data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN.
Ditangquan exercises based on safe-landing strategies prevent falls and injury among older individuals with sarcopenia
Authors: Li Zhen-rui , Ma Yun-jing , Zhuang Jie , Tao Xun-chen , Guo Chao-yang , Liu Shu-ting , Zhu Ran-ran , Wang Jin-xiang , Fang Lei 
Published: August 2022

BackgroundSarcopenia is the age-related loss of skeletal muscle mass and function; it is a risk factor for falls among older individuals. Few studies have focused on training such individuals to adopt a safe-landing strategy that would protect them from fall-related injuries. Ditangquan is a traditional Chinese martial art comprising movements that conform to the principles of safe landing. This study aims to investigate the effectiveness of Ditangquan in preventing fall-related injuries among older individuals with sarcopenia.MethodsA total of 70 participants (21 males and 49 females with sarcopenia) between 60 and 80 years of age were recruited from three local communities and randomly assigned to the Ditangquan exercise group (DG) or the control group (CG) in a 1:1 ratio. Three times a week for 24 weeks, both the DG and CG received an hour of conventional exercise and an hour of Ditangquan exercise based on safe landing. Primary outcomes were the modified falls efficacy scale (MFES), the number of falls, and fall injuries; the secondary outcome was the Timed Up &amp; Go (TUG) test.ResultsThe DG had significantly fewer falls (1 vs. 8, P = 0.028) and fall injuries (0 vs. 6, P = 0.025) than the CG. Furthermore, at the end of the study, the DG had a significantly improved MFES (mean difference: 32.17 scores; 95% CI: 21.32, 43.02; P &lt;0.001) and TUGT (mean difference: −4.94 s; 95% CI: −7.95, −1.93; P = 0.002) as compared with the CG.ConclusionDitangquan exercise based on the safe-landing strategy effectively improves the functional mobility of the elderly, reduces the occurrence of falls and injuries, and increases the individual's confidence in preventing falls.
Patients with seronegative rheumatoid arthritis have a different phenotype than seropositive patients: A clinical and ultrasound study
Authors: Carbonell-Bobadilla Natalia , Soto-Fajardo Carina , Amezcua-Guerra Luis M. , Batres-Marroquín Ana Beatriz , Vargas Tania , Hernández-Diazcouder Adrian , Jiménez-Rojas Valentin , Medina-García Ana Cristina , Pineda Carlos , Silveira Luis H. 
Published: August 2022

IntroductionRheumatoid arthritis (RA) is an inflammatory disease whose clinical phenotype largely depends on the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Seronegative RA appears to be a less severe disease, but this remains controversial. This study aimed to assess whether seronegative patients show a less severe disease than seropositive patients.MethodsA cross-sectional study was conducted on RA outpatients from a single center. Clinical activity scales, laboratory evaluations, and cardiovascular risk scores were assessed. Musculoskeletal ultrasound (US) examinations were performed.ResultsOne hundred and fourteen patients were enrolled. Eighty-five were seropositive (76% women) and 29 seronegative (93% women). Seropositive patients had a younger age at disease onset (43 ± 14 vs. 54 ± 11; p = 0.001) and used sulfasalazine (47 vs. 17%; p = 0.004) and glucocorticoids (36 vs. 10%; p = 0.007) more frequently. No differences in clinical activity scales and in 10-year cardiovascular risk were observed. Pathological US data were found more frequently in seropositive patients in the 2nd metacarpophalangeal (MCP) joint, both in grayscale (71 vs. 38%; p = 0.008) and in power Doppler (PD; 53 vs. 9%; p &lt; 0.001); erosions (36 vs. 9%; p = 0.020) were also more frequent. We found greater severity of PD signals in the 2nd MCP and 3rd MCP joints of the seropositive patients, while synovitis severity was higher only in the 2nd MCP joints. The percentage of total joints with erosions (9 vs. 1%; p &lt; 0.001) and 2nd MCP joints with erosions (25 vs. 7%; p &lt; 0.001) was higher in seropositive patients.ConclusionRA patients show a differentiated phenotype according to their ACPA and RF status. In seronegative patients, RA begins later in life and has a lower requirement for antirheumatic therapies. On US evaluation, seropositive patients show more joint damage, especially in MCP joints. Despite this, long-term cardiovascular risk is similar among RA patients, regardless of their RF and ACPA status.
ASNS can predict the poor prognosis of clear cell renal cell carcinoma
Authors: Gan Xinqiang , Liu Ruiji , Cheng Hong , Mao Weipu , Feng Ninghan , Chen Ming 
Published: August 2022

PurposeClear cell renal cell carcinoma (ccRCC) is one of the most common malignancies of the urinary system. This study was conducted to discover a new target that can predict the prognosis and promote the treatment of ccRCC.MethodsThe raw data were downloaded from the TCGA database, and the predictive value of ASNS for various clinicopathological features was verified in the following analysis. Then, we analyzed the potential involvement of ASNS in tumor immunity and obtained the possible pathways involving ASNS through GO/KEGG enrichment analysis and GSEA. We also further verified our findings in pathological specimens of ccRCC patients.ResultsASNS expression was significantly increased in ccRCC, which was associated with advanced clinicopathological characteristics. It was an independent prognostic factor for overall survival in 535 patients with ccRCC. Immune cell infiltration analysis revealed that ASNS expression was related to T lymphocyte infiltration of tumors and poor prognosis. Moreover, we performed relevant functional enrichment analyses of ASNS.ConclusionsASNS might play a significant role in the development and immune cell infiltration of ccRCC and serve as a valuable clinical prognostic biomarker.
Prognostic value of normal sodium levels in patients with metastatic renal cell carcinoma receiving tyrosine kinase inhibitors
Authors: Roviello Giandomenico , Catalano Martina , De Giorgi Ugo , Maruzzo Marco , Buti Sebastiano , Gambale Elisabetta , Procopio Giuseppe , Ottanelli Carlotta , Caliman Enrico , Isella Luca , Sepe Pierangela , Brighi Nicole , Santoni Matteo , Galli Luca , Conca Raffaele , Doni Laura , Antonuzzo Lorenzo 
Published: August 2022

BackgroundAlthough serum sodium concentration, particularly hyponatremia, has been shown to be a prognostic marker of survival in metastatic renal cell carcinoma (mRCC), the impact of normal sodium levels has not been investigated. Herein, we investigate the influence of normonatremia in mRCC patients treated with tyrosine kinase inhibitors (TKIs).Materials and methodsFor this retrospective study, the clinical and biochemical data of patients treated with first-line TKIs for mRCC were available from seven Italian cancer centers. We collected natremia levels at baseline and first evaluation after treatment excluding patients with sodium levels outside the normal range (&lt;135 or &gt;145 mEq/L). The remaining patients were subdivided into two groups according to the median sodium value: natremia patients with &lt;140 mEq/L (n = 132) and baseline natremia patients with ≥140 mEq/L (n = 185). Subsequently, we analyzed the impact of sodium levels on response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). PFS and OS were estimated through the Kaplan–Meier method, and differences between groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were applied to evaluate the prognostic factors for PFS and OS.ResultsOf the 368 patients, 317 were included in the analysis, 73.1% were men, and the median age was 67 years (range 36–89). When comparing patients with baseline natremia ≥140 mEq/L (n = 185) to patients with natremia &lt;140 mEq/L (n = 132), the PFS was 15 vs. 10 months (p &lt; 0.01) and the OS was 63 vs. 36 months, respectively (p = 0.02). On the first evaluation, patients with serum sodium ≥140 mEq/L had longer PFS (15 vs. 10 months, p &lt; 0.01) and OS (70 vs. 32 months, p &lt; 0.01) than patients with levels &lt;140 mEq/L. Moreover, clinical outcomes showed a significant improvement in patients with natremia ≥140 mEq/L compared with patients with levels &lt;140 mEq/L both at baseline and first evaluation: PFS was 19 vs. 11 months (p &lt; 0.01) and OS was 70 vs. 36 months (p &lt; 0.01), respectively.ConclusionsTo the best of our knowledge, this is the first study to investigate the impact of normonatremia in mRCC. We found that serum sodium levels &lt;140 mEq/L at baseline and first assessment are independently associated with worse PFS and OS in mRCC patients treated with TKIs in the first-line setting.
Parental perceptions and the 5C psychological antecedents of COVID-19 vaccination during the first month of omicron variant surge: A large-scale cross-sectional survey in Saudi Arabia
Authors: Alenezi Shuliweeh , Alarabi Mohammed , Al-Eyadhy Ayman , Aljamaan Fadi , Elbarazi Iffat , Saddik Basema , Alhasan Khalid , Assiri Rasha , Bassrawi Rolan , Alshahrani Fatimah , Alharbi Nasser S. , Fayed Amel , Minhaj Ahmed Sheikh , Halwani Rabih , Saad Khaled , Alsubaie Sarah , Barry Mazin ,   COVID-19 Saudi Research Consortium, Memish Ziad A. , Al-Tawfiq Jaffar A. , Temsah Mohamad-Hani 
Published: August 2022

BackgroundWith the rapid surge of SARS-CoV-2 Omicron variant, we aimed to assess parents' perceptions of the COVID-19 vaccines and the psychological antecedents of vaccinations during the first month of the Omicron spread.MethodsA cross-sectional online survey in Saudi Arabia was conducted (December 20, 2021-January 7, 2022). Convenience sampling was used to invite participants through several social media platforms, including WhatsApp, Twitter, and email lists. We utilized the validated 5C Scale, which evaluates five psychological factors influencing vaccination intention and behavior: confidence, complacency, constraints, calculation, and collective responsibility.ResultsOf the 1,340 respondents, 61.3% received two doses of the COVID-19 vaccine, while 35% received an additional booster dose. Fify four percentage were unwilling to vaccinate their children aged 5–11, and 57.2% were unwilling to give the additional booster vaccine to children aged 12–18. Respondents had higher scores on the construct of collective responsibility, followed by calculation, confidence, complacency, and finally constraints. Confidence in vaccines was associated with willingness to vaccinate children and positively correlated with collective responsibility (p &lt; 0.010). Complacency about COVID-19 was associated with unwillingness to vaccinate older children (12–18 years) and with increased constraints and calculation scores (p &lt; 0.010). While increasing constraints scores did not correlate with decreased willingness to vaccinate children (p = 0.140), they did correlate negatively with confidence and collective responsibility (p &lt; 0.010).ConclusionsThe findings demonstrate the relationship between the five antecedents of vaccination, the importance of confidence in vaccines, and a sense of collective responsibility in parents' intention to vaccinate their children. Campaigns addressing constraints and collective responsibility could help influence the public's vaccination behavior.
Modern drug self-medication and associated factors among pregnant women at Settat city, Morocco
Authors: Chergaoui Samia , Changuiti Omaima , Marfak Abdelghafour , Saad Elmadani , Hilali Abderraouf , Youlyouz Marfak Ibtissam 
Published: August 2022

Purpose: The consumption of drugs during pregnancy without medical advice constitutes a risk for the mother and the fetus. It is a public health problem. This study aimed to assess self-medication practices among pregnant women, the most used medicines, and factors associated with this practice.Methods: A cross-sectional study was conducted using a structured questionnaire on pregnant women who were attending Settat health centers. A simple random sampling technique was used to select the study participants. Descriptive and inferential statistics were computed using the SPSS version 19.Results: Among 364 pregnant women, 118 (32%) practiced self-medication in modern medicine. Paracetamol was the most used medication, and nausea and vomiting were the most frequent symptoms reported by self-medicated pregnant women. Multivariate logistic regression analysis showed that women over 30 years old were four-fold more likely to practice self-medication than the other groups [AOR: 4.19; 95% CI (1.80–9.77)]. Similarly, unemployed women [AOR: 3.93; 95% CI (0.80–19.23)], those in third trimester [AOR: 2.63; 95% CI (1.29–5.36)], multiparous [AOR: 6.03; 95% CI (3.12–11.65)], without chronic illness [AOR: 2.84; 95% CI (1.26–6.41)], without therapeutic treatment [AOR: 10.1; 95% CI (2.81–37.03)] and who have attended ANC at least once, were more likely to practice self-medication than the other groups.Conclusion: The prevalence of modern drug self-medication among pregnant women in Morocco is classified as lower. Health professionals can exert positive pressure through education and information provided during ANC about OTC medications to significantly reduce the rate of self-medication.
Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment
Authors: Ye Lingling , You Xiang , Zhou Jie , Wu Chaohui , Ke Meng , Wu Wanhong , Huang Pinfang , Lin Cuihong 
Published: August 2022

Background and Objective: Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated.Methods: A physiologically based pharmacokinetic (PBPK) model of daptomycin was established and validated to simulate its disposition in healthy populations and adults with renal impairment, along with a daptomycin exposure simulated in pediatric patients with renal impairment.Results: The simulated PBPK modeling results for various regimens of intravenously administered daptomycin were consistent with observed data according to the fold error below the threshold of 2. The Cmax and AUC of daptomycin did not differ significantly between children with mild-to-moderate renal impairment and healthy children. The AUC increased by an average of 1.55-fold and 1.85-fold in severe renal impairment and end-stage renal disease, respectively. The changes were more significant in younger children and could reach a more than 2-fold change. This scenario necessitates further daptomycin dose adjustments.Conclusion: Dose adjustments take into account the efficacy and safety of the drug; however, the steady-state Cmin of daptomycin may be above 24.3 mg/L in a few instances. We recommend monitoring creatine phosphokinase more than once a week when using daptomycin in children with renal impairment.
Real-world association of adherence with outcomes and economic burden in patients with tuberculosis from South Korea claims data
Authors: Kwon Sun-Hong , Nam Jin Hyun , Kim Hye-Lin , Park Hae-Young , Kwon Jin-Won 
Published: August 2022

Objectives: We analyzed tuberculosis (TB)-related costs according to treatment adherence, as well as the association between treatment adherence, treatment outcomes, and costs related to drug-susceptible TB in South Korea.Methods: Patients who had newly treated TB in South Korea between 2006 and 2015 were selected from nationwide sample claims data and categorized into adherent and non-adherent groups using the proportion of days TB drugs covered. Patients were followed-up from the initiation of TB treatment. The mean five-year cumulative costs per patient were estimated according to adherence. Moreover, we evaluated the relative ratios to identify cost drivers such as adherence, treatment outcomes, and baseline characteristics using generalized linear models. Four treatment outcomes were included: treatment completion, loss to follow-up, death, and the initiation of multidrug-resistant TB treatment.Results: Out of the 3,799 new patients with TB, 2,662 were adherent, and 1,137 were non-adherent. Five years after initiating TB treatment, the mean TB-related costs were USD 2,270 and USD 2,694 in the adherent and non-adherent groups, respectively. The TB-related monthly cost per patient was also lower in the adherent than in the non-adherent (relative ratio = 0.89, 95% CI 0.92–0.98), while patients who were lost to follow-up spent more on TB-related costs (2.52, 2.24–2.83) compared to those who completed the treatment.Conclusion: Non-adherent patients with TB spend more on treatment costs while they have poorer outcomes compared to adherent patients with TB. Improving patient adherence may lead to effective treatment outcomes and reduce the economic burden of TB. Policymakers and providers should consider commitment programs to improve patient’s adherence.
Optimal target blood pressure in critically ill adult patients with vasodilatory shock: A systematic review and meta-analysis
Authors: Yoshimoto Hidero , Fukui Satoshi , Higashio Koki , Endo Akira , Takasu Akira , Yamakawa Kazuma 
Published: August 2022

While the Surviving Sepsis Campaign guidelines recommend an initial target value of 65 mmHg as the mean arterial pressure (MAP) in patients with septic shock, the optimal MAP target for improving outcomes remains controversial. We performed a meta-analysis to evaluate the optimal MAP for patients with vasodilatory shock, which included three randomized controlled trials that recruited 3,357 patients. Between the lower (60–70 mmHg) and higher (&gt;70 mmHg) MAP target groups, there was no significant difference in all-cause mortality (risk ratio [RR], 1.06; 95% confidence intervals [CI], 0.98–1.16) which was similar in patients with chronic hypertension (RR, 1.10; 95% CI, 0.98–1.24) and patients aged ≥65 years (RR, 1.10; 95% CI, 0.99–1.21). No significant difference in adverse events was observed between the different MAP groups (RR, 1.04; 95% CI, 0.87–1.24); however, supraventricular arrhythmia was significantly higher in the higher MAP group (RR, 1.73; 95% CI, 1.15–2.60). Renal replacement therapy was reduced in the higher MAP group of patients with chronic hypertension (RR, 0.83; 95% CI, 0.71–0.98). Though the higher MAP control did not improve the mortality rate, it may be beneficial in reducing renal replacement therapy in patients with chronic hypertension.Systematic review registration: UMIN Clinical Trials Registry, identifier UMIN000042624