bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expert consensus on the management of systemic sclerosis-associated interstitial lung disease
Authors: Rahaghi Franck F. , Hsu Vivien M. , Kaner Robert J. , Mayes Maureen D. , Rosas Ivan O. , Saggar Rajan , Steen Virginia D. , Strek Mary E. , Bernstein Elana J. , Bhatt Nitin , Castelino Flavia V. , Chung Lorinda , Domsic Robyn T. , Flaherty Kevin R. , Gupta Nishant , Kahaleh Bashar , Martinez Fernando J. , Morrow Lee E. , Moua Teng , Patel Nina , Shlobin Oksana A. , Southern Brian D. , Volkmann Elizabeth R. , Khanna Dinesh 
Published: January 2023

Abstract
Background
Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD.

Methods
A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤  − 2.5 or ≥  + 2.5 with a standard deviation not crossing zero.

Results
Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants.

Conclusions
This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.
Ghost messages: cell death signals spread
Authors: Zhang Mingming , Lin Yuan , Chen Ruijing , Yu Haikuan , Li Yi , Chen Ming , Dou Ce , Yin Pengbin , Zhang Licheng , Tang Peifu 
Published: January 2023

AbstractCell death is a mystery in various forms. Whichever type of cell death, this is always accompanied by active or passive molecules release. The recent years marked the renaissance of the study of these molecules showing they can signal to and communicate with recipient cells and regulate physio- or pathological events. This review summarizes the defined forms of messages cells could spread while dying, the effects of these signals on the target tissue/cells, and how these types of communications regulate physio- or pathological processes. By doing so, this review hopes to identify major unresolved questions in the field, formulate new hypothesis worthy of further investigation, and when possible, provide references for the search of novel diagnostic/therapeutics agents.
Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease
Authors: Shao Congxiang , Xu Lishu , Lei Pingguang , Wang Wei , Feng Shiting , Ye Junzhao , Zhong Bihui 
Published: January 2023

AbstractBackground/aimsNonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon.MethodsThis prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement.ResultsThe study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67,p = 0.03; 0.79,p = 0.02; 0.63,p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92,p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71,p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73,p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls.ConclusionsDiagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS.Trial registrationThe study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197)Graphical Abstract
A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma
Authors: Yu Lu-Lu , Hu Bi-Wen , Huang Han-Xue , Yu Bing , Xiao Qi , Lv Qiao-Li , Luo Chen-Hui , Guo Cheng-Xian , Li Jin-Gao , Xie Xiao-Xue , Yin Ji-Ye 
Published: January 2023

Abstract
Background
Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC.

Methods
This was a large‑scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC.

Results
After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10− 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy.

Conclusion
Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients.
Trial registration number: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546.
Study on the treatment of postmenopausal osteoporosis with quercetin in Liuwei Dihuang Pill based on network pharmacology
Authors: Zhu Fuping , Li Wuping , Wang Linhua , Dai Bing , Liu Zongyi , Wu Hang , Deng Ting 
Published: January 2023

Abstract
Background
Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored.

Methods
Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry.

Results
Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling.

Conclusion
Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.
The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants
Authors: Sánchez Rosario , Ripoll-Vera Tomás , López-Mendoza Manuel , de Juan-Ribera Joaquín , Gimeno Juan Ramón , Hermida Álvaro , Ruz-Zafra María Aurora , Torregrosa José Vicente , Mora Antonia , García-Pinilla José Manuel , Fortuny Elena , Aguinaga-Barrilero Ana , Torra Roser 
Published: January 2023

Abstract
Background
Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort.

Results
Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively).

Conclusions
Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
Which endometrial preparation protocol provides better pregnancy and perinatal outcomes for endometriosis patients in frozen-thawed embryo transfer cycles? A retrospective study on 1413 patients
Authors: Guo Yaxin , Fang Zishui , Yu Lin , Sun Xin , Li Fei , Jin Lei 
Published: January 2023

Abstract
Objective
To determine the optimal endometrial preparation protocol for a frozen embryo transfer in patients with endometriosis.

Design
Retrospective cohort study.

Setting
Tertiary care academic medical center.

Patient(s)
One thousand four hundred thirteen patients with endometriosis who underwent oocyte aspiration from 2015 to 2020 and frozen embryo transfer from 2016 to 2020 and received natural cycle, hormone replacement treatment with or without GnRHa pretreatment endometrial preparation.

Intervention(s)
None.

Main outcome measure(s)
Clinical pregnancy rate, live birth rate, miscarriage rate, multiple pregnancy rate, biochemical pregnancy rate and ectopic pregnancy rate. Singleton live births were assessed for perinatal outcomes and obstetric complications.

Result(s)
There were no differences in clinical pregnancy outcomes or prenatal outcomes among the three commonly used endometrial preparation protocols for frozen embryo transfer cycles in patients with endometriosis. Results remained after screening variables using univariate logistic regression into multivariate logistic regression. No advantages or disadvantages were found among the three endometrial preparation protocols in patients with endometriosis.

Conclusion(s)
Natural cycle, hormone replacement cycle, or hormone replacement treatment with GnRHa pretreatment showed no superiority or inferiority in pregnancy and perinatal outcomes in patients with endometriosis.
Virulence factors and mechanisms of paediatric pneumonia caused by Enterococcus faecalis
Authors: Tian Zhiying , Khan Asif Iqbal , Rehman Ata Ur , Deng Ting , Ma Chao , Wang Liang 
Published: January 2023

AbstractPaediatric pneumonia is a respiratory infection that affects infants and young children under the age of 3. This disease is the leading cause of infant and child mortality in developing countries because of the weak immune system of young children. The difficulty and length of time required to identify the pathogen and causative agent are the main reasons for this high mortality rate. In addition, the identification of certain causative agents is particularly important for the treatment of paediatric pneumonia. In this study, we explored the possible mechanisms by which pathogenic Enterococcus faecalis induced pneumonia in vivo. The potential virulence factors of bacteria isolated from the intestines of paediatric pneumonia patients were determined. Taken together, the results suggested that lysophosphatidic acid (LTA) from pathogenic E. faecalis decreases the expression of platelet-activating factor receptor (PAFR), which in turn disrupts the function of intestinal tight junctions (Occ and Ccldn1), leading to the entry of LE-LTA into the bloodstream because of the disruption of the intestinal barrier. Although LTA can enter circulation, it cannot directly infiltrate the lungs, which indicates that lung inflammation in mice is not caused by the direct entry of LE-LTA into the lungs. We further found that LTA activates immune cells, such as CD8 + T cells and type 2 innate lymphocytes, in vivo. Interleukin-6 and interleukin-17 can produce large amounts of inflammatory factors and thus promote the development of pneumonia. In conclusion, our findings demonstrate that the LTA of pathogenic E. faecalis in the intestine is a virulence factor that can cause paediatric pneumonia. This study found that intestinal bacterial virulence factors can induce immune responses in the lungs and blood. These findings could provide further insight into the mechanism of infectious diseases in the lung that are caused by bacteria in the intestine.
Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study
Authors: Shang Xianwen , Roccati Eddy , Zhu Zhuoting , Kiburg Katerina , Wang Wei , Huang Yu , Zhang Xueli , Zhang Xiayin , Liu Jiahao , Tang Shulin , Hu Yijun , Ge Zongyuan , Yu Honghua , He Mingguang 
Published: January 2023

AbstractBackgroundLittle is known regarding whether sex assigned at birth modifies the association between several predictive factors for dementia and the risk of dementia itself.MethodsOur retrospective cohort study included 214,670 men and 214,670 women matched by age at baseline from the UK Biobank. Baseline data were collected between 2006 and 2010, and incident dementia was ascertained using hospital inpatient or death records until January 2021. Mediation analysis was tested for 133 individual factors.ResultsOver 5,117,381 person-years of follow-up, 5928 cases of incident all-cause dementia (452 cases of young-onset dementia, 5476 cases of late-onset dementia) were documented. Hazard ratios (95% CI) for all-cause, young-onset, and late-onset dementias associated with the male sex (female as reference) were 1.23 (1.17–1.29), 1.42 (1.18–1.71), and 1.21 (1.15–1.28), respectively. Out of 133 individual factors, the strongest mediators for the association between sex and incident dementia were multimorbidity risk score (percentage explained (95% CI): 62.1% (45.2–76.6%)), apolipoprotein A in the blood (25.5% (15.2–39.4%)), creatinine in urine (24.9% (16.1–36.5%)), low-density lipoprotein cholesterol in the blood (23.2% (16.2–32.1%)), and blood lymphocyte percentage (21.1% (14.5–29.5%)). Health-related conditions (percentage (95% CI) explained: 74.4% (51.3–88.9%)) and biomarkers (83.0% (37.5–97.5%)), but not lifestyle factors combined (30.1% (20.7–41.6%)), fully mediated sex differences in incident dementia. Health-related conditions combined were a stronger mediator for late-onset (75.4% (48.6–90.8%)) than for young-onset dementia (52.3% (25.8–77.6%)), whilst lifestyle factors combined were a stronger mediator for young-onset (42.3% (19.4–69.0%)) than for late-onset dementia (26.7% (17.1–39.2%)).ConclusionsOur analysis matched by age has demonstrated that men had a higher risk of all-cause, young-onset, and late-onset dementias than women. This association was fully mediated by health-related conditions or blood/urinary biomarkers and largely mediated by lifestyle factors. Our findings are important for understanding potential mechanisms of sex in dementia risk.
The relationship between the insulinemic potential of diet and lifestyle and risk of breast cancer: a case-control study among iranian adult women
Authors: Mokhtari Ebrahim , Jamshidi Sanaz , Daftari Ghazal , Farhadnejad Hossein , Teymoori Farshad , Momeni Seyed Aref , Rashidkhani Bahram , Mirmiran Parvin 
Published: January 2023

AbstractBackgroundBreast cancer (BC) is the most prevalent cancer, with a higher mortality rate in women worldwide. We aimed to investigate the association of the insulinemic potential of diet and lifestyle with the odds of BC using empirical indices, including the empirical dietary index for hyperinsulinemia (EDIH), empirical lifestyle index for hyperinsulinemia (ELIH), the empirical dietary index for insulin resistance (EDIR), and empirical lifestyle index for insulin resistance (ELIR).MethodsThis hospital-based case-control study was conducted among Tehranian adult women aged≥30 years. The final analysis was performed on 134 women newly diagnosed with histologically confirmed BC as a case and 267 healthy women of the same age as control. A 168-food item food frequency questionnaire was used for assessing dietary intakes at baseline. The odds ratios (ORs) and 95% confidence intervals (CIs) of BC across tertiles of EDIH, ELIH, EDIR, and ELIR were determined using multivariable-adjusted logistic regression.ResultsThe mean ± SD of age and BMI of participants were 47.9±10.3 years and 29.4±5.5 kg/m2, respectively. EDIH score was related to the higher risk of BC based on fully adjusted models (OR:2.24;95%CI:1.21–4.12, Ptrend=0.016). Furthermore, subgroup analysis showed a higher BC risk with increasing EDIH score in postmenopausal women (OR:1.74, 95%CI:1.13-2.69) and those without a history of the oral contraceptive pill (OCP) use (OR:1.44;95%CI:1.02–2.04). Moreover, ELIH scores were positively associated with an increased risk of BC in postmenopausal women (OR; 1.98; 95% CI: 1.35 – 2.89), those with a family history of cancer (OR:1.94;95%CI:1.10–3.42), and in individuals who did not use OCP (OR:1.46; 95% CI:1.00–2.12).ConclusionOur results showed a possible link between EDIH and higher BC risk. Also, higher EDIH and ELIH scores were strongly associated with a higher risk of BC in postmenopausal women, those with a family history of BC, and those who do not use OCP.