bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative safety of infliximab and adalimumab on pregnancy outcomes of women with inflammatory bowel diseases: a systematic review & meta-analysis
Authors: Wang Han , Hu Yue , Chen Fang , Shen Mengdie 
Published: November 2022

Abstract
Background
Inflammatory bowel disease (IBD) is a condition that affects most of the digestive tract. There is no report of fertility reduction in medically managed IBD women compared with the general population. On the other hand, active IBD can lead to significantly decreased fertility. Over the previous 2 decades, anti-tumor necrosis factor (anti-TNF) has been an effective treatment for managing patients with IBD, increasing the use of infliximab and adalimumab in clinical practice. However, it is unclear which biologics are better for pregnant women with IBD.

Aim
We conducted a systematic review and meta-analysis for the risk of adverse pregnancy outcomes following treatment with infliximab and adalimumab in women with IBD.

Methods
Bibliographic databases were retrieved from their inception to July 2022. The results were adverse pregnancy outcomes, including congenital malformations and spontaneous abortion.

Results
A total of 8 studies included 527 pregnant women with IBD. Of these, 343 received infliximab, and 184 received adalimumab therapy. Compared to adalimumab, adverse pregnancy outcomes were not increased in infliximab therapy including congenital malformations and spontaneous abortion.

Conclusion
Infliximab and adalimumab therapy did not show the difference of risk in adverse pregnancy outcomes in women with IBD.

Systematic review registration
http://www.crd.york.ac.uk/PROSPERO, identifier: CRD 42,021,277,869.
Differential in vitro effects of targeted therapeutics in primary human liver cancer: importance for combined liver cancer
Authors: Malik Ihtzaz Ahmed , Rajput Mansi , Werner Rieke , Fey Dorothea , Salehzadeh Niloofar , von Arnim Christine A. F. , Wilting Jörg 
Published: November 2022

AbstractThe incidence of primary liver tumors, hepatocellular carcinoma (HCC), intrahepatic cholangiocellular carcinoma (ICC), and combined HCC/ICC (cHCC/CC) is increasing. For ICC, targeted therapy exists only for a small subpopulation of patients, while for HCC, Sorafenib and Lenvatinib are in use. Diagnosis of cHCC/CC is a great challenge and its incidence is underestimated, bearing the risk of unintended non-treatment of ICC. Here, we investigated effects of targeted inhibitors on human ICC cell lines (HUH28, RBE, SSP25), in comparison to extrahepatic (E)CC lines (EGI1, CCC5, TFK1), and HCC/hepatoblastoma cell lines (HEP3B, HUH7, HEPG2). Cells were challenged with: AKT inhibitor MK-2206; multikinase inhibitors Sorafenib, Lenvatinib and Dasatinib; PI3-kinase inhibitors BKM-120, Wortmannin, LY294002, and CAL-101; and mTOR inhibitor Rapamycin. Dosage of the substances was based on the large number of published data of recent years. Proliferation was analyzed daily for four days. All cell lines were highly responsive to MK-2206. Thereby, MK-2206 reduced expression of phospho(p)-AKT in all ICC, ECC, and HCC lines, which mostly corresponded to reduction of p-mTOR, whereas p-ERK1/2 was upregulated in many cases. Lenvatinib showed inhibitory effects on the two HCC cell lines, but not on HEPG2, ICCs and ECCs. Sorafenib inhibited proliferation of all cells, except the ECC line CCC5. However, at reduced dosage, we observed increased cell numbers in some ICC experiments. Dasatinib was highly effective especially in ICC cell lines. Inhibitory effects were observed with all four PI3-kinase inhibitors. However, cell type-specific differences were also evident here. Rapamycin was most effective in the two HCC cell lines. Our studies show that the nine inhibitors differentially target ICC, ECC, and HCC/hepatoblastoma lines. Caution should be taken with Lenvatinib and Sorafenib administration in patients with cHCC/CC as the drugs may have no effects on, or might even stimulate, ICC.
Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA
Authors: Oh Tae Jeong , Lim Eunkyung , Bang Bo-Ram , Lee Justin Junguek , Na Yong Gil , Shin Ju Hyun , Lim Jae Sung , Song Ki Hak , An Sungwhan 
Published: November 2022

Abstract
Background
Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa.

Methods
CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1—T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0.

Results
CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 – 95.5%), a specificity of 92.5% (95% CI: 85.7 – 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 – 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa.

Conclusions
In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.
Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas
Authors: Yang Yueyang , Tang Peng , Ma Mingquan , Zhang Hongdian , Wang Haitong , Zhu Kai , Xiao Wanyi , Gong Lei , Yu Zhentao 
Published: November 2022

Abstract
Background
Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC).

Methods
In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group).

Results
No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045).

Conclusions
S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.
Impact of fibrinogen levels and modified Glasgow prognostic score on survival of stage III/N2 non-small cell lung cancer patients treated with neoadjuvant therapy and radical resection
Authors: Sinn Katharina , Mosleh Berta , Grusch Michael , Klepetko Walter , Hoetzenecker Konrad , Klikovits Thomas , Gompelmann Daniela , Hoda Mir Alireza 
Published: November 2022

Abstract
Purpose
The prognostic value of pretreatment and preoperative fibrinogen plasma levels and the modified Glasgow prognostic score (mGPS) in stage III/N2 non-small cell lung cancer (NSCLC) patients who receive neoadjuvant treatment followed by radical surgery is yet unclear.

Methods
Fibrinogen levels and mGPS of 84 patients with initial stage III/N2 NSCLC, who received neoadjuvant therapy followed by complete surgical resection from 2002 to 2014 were retrospectively analyzed and correlated with clinical parameters and overall survival (OS). Data were analyzed using log-rank and Cox regression analysis adjusted for clinical and pathological factors.

Results
Median serum fibrinogen level after neoadjuvant treatment was 439 mg/dL (IQR 158 mg/dL). Elevated fibrinogen levels (> 400 mg/dL) after neoadjuvant treatment were significantly associated with poorer OS (28.2 months vs. 60.9 months, HR 0.562, p = 0.048). Importantly, a decrease in fibrinogen levels after neoadjuvant treatment (n = 34) was found to be an independent predictor for favorable OS in multivariate analysis (HR 0.994, p = 0.025). Out of 80 patients, 55, 19 and 6 patients had a mGPS of 0, 1 and 2, respectively. Moreover, elevated mGPS after neoadjuvant treatment (mGPS 1–2) showed a non-significant trend for poorer OS compared to mGPS 0 (28.2 vs. 46.5 months, HR 0.587, p = 0.066).

Conclusion
Elevated fibrinogen levels after neoadjuvant therapy prior to surgery in stage III/N2 NSCLC patients are associated with significant disadvantage for OS. A decrease in fibrinogen levels after neoadjuvant therapy was found to be a predictor for superior OS in this retrospective patient cohort.
Dentate line invasion as a predictive factor of poor distant relapse-free survival in locally advanced lower rectal cancer with anal sphincter involvement
Authors: Song Maxiaowei , Wang Hongzhi , Wang Lin , Li Shuai , Zhang Yangzi , Geng Jianhao , Zhu Xianggao , Li Yongheng , Cai Yong , Wang Weihu 
Published: November 2022

Abstract
Background
While an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery.

Methods
We analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched.

Results
Before matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P < 0.001), disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P < 0.001) and after matching (48.0% vs. 20.0%, P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000).

Conclusions
DLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.
Impact of posttransplant cyclophosphamide on the outcome of patients undergoing unrelated single-unit umbilical cord blood transplantation for pediatric acute leukemia
Authors: Li Xin-Yu , Zhan Li-Ping , Liu Dian-Dian , Han Xia-Wei , Chen Han , Wu Zheng-Zhou , Wang Yin , Que Li-Ping , Wu Xiao-Jun , Liu Su , Wang Kai-Mei , Huang Shao-Liang , Fang Jian-Pei , Huang Ke , Xu Hong-Gui 
Published: November 2022

Abstract
Background
Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia.

Methods
This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared.

Results
The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups.

Conclusion
The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.
The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy
Authors: Zhu Zhe , Zou He , Li Chuanyu , Tong Bainan , Zhang Chenchen , Xiao Jun 
Published: November 2022

Abstract
Background
This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis.

Methods
Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients.

Results
Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy.

Conclusions
RPE and choroidal atrophy were found to play an important role in the development of macular caldera.
Optical coherence tomography findings in three patients with Werner syndrome
Authors: Nagai Tatsuya , Yokouchi Hirotaka , Miura Gen , Koshizaka Masaya , Maezawa Yoshiro , Oshitari Toshiyuki , Yokote Koutaro , Baba Takayuki 
Published: November 2022

Abstract
Background
Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis.

Case presentation
We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma.
The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT.

Conclusions
Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.
Outcomes of retinal pigment epithelial detachment in Vogt-Koyanagi-Harada disease: a longitudinal analysis
Authors: Zheng Chuanzhen , Wang Kaixuan , Zhang Mi , Tao Qingqin , Li Xiaorong , Zhang Xiaomin 
Published: November 2022

Abstract
Background
The aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course.

Methods
The retrospective study enrolled a total of 470 eyes with VKH, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (the CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups.

Results
CSC developed at the site of the PED in 5 of the 12 eyes with PED, while in the remaining 7 eyes PED gradually resolved following therapy. The prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P = 0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P = 0.03).

Conclusion
PEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of classic CSC in VKH cases.
The effect of family integrated care on the prognosis of premature infants
Authors: Chen Hongyu , Dong Le 
Published: November 2022

Abstract
Background
The purpose of this study was to investigate the effect of family integrated care (FICare) on the prognosis of children hospitalized with preterm infants.

Methods
Two hundred thirty preterm infants admitted to our hospital from January 2019 to April 2021 were enrolled in a prospective randomized study and divided into 115 cases in the intervention group and 115 cases in the control group according to the random number table method, and given the FICare and the conventional care, respectively. The duration of nasogastric tube retention, time to achieve total enteral nutrition, rate of weight gain, exclusive breastfeeding rate, length of hospital stay, growth and development, readmission rate, parental self-efficacy, family functioning and complications related to prematurity were compared between the two groups.

Results
Compared with the control group, the intervention group had shorter nasogastric tube retention time, shorter time to achieve total enteral nutrition, higher exclusive breastfeeding rate, shorter time of hospital stay and better growth rate. Before the intervention, there was no difference in parental self-efficacy and family functioning between the two groups; after the intervention, the intervention group had higher parental self-efficacy and higher ratings of family functioning, and the difference was statistically significant. Compared with the control group, the intervention group had a lower readmission rate and significantly lower incidence of infection and choking.

Conclusion
The FICare can shorten the time of nasogastric tube retention, shorten time to achieve total enteral nutrition and hospital stay, increase the rate of exclusive breastfeeding and the rate of weight gain, finally improve the prognosis of preterm infants and have a positive effect on parents.
Familial Hemophagocytic Lymphohistiocytosis secondary to UNC13D mutation: a report of two cases
Authors: Sadeghi Payman , Esslami Golnaz Ghazizadeh , Rokni-Zadeh Hassan , Changi-Ashtiani Majid , Mohsenipour Reihaneh 
Published: November 2022

Abstract
Background
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by some clinical signs (e.g., non-remitting fever, hepatosplenomegaly) and laboratory findings (e.g., cytopenia, increased ferritin level, hypofibrinogenemia, lipid disorders, coagulopathy, and multiple organ failure). Depending on the etiology, HLH is divided into familial (i.e., primary) and acquired (i.e., secondary) forms. Familial HLH (FHL), an autosomal recessive condition, is classified into five subtypes based on underlying genetic defects. The PRF1, STX11, UNC13D, HPLH1, and STXBP2 are the most well-known genes of this type which are related to granule-mediated cytotoxic T and Natural killer (NK) cells. The treatment is based on the HLH-2004 protocol.

Case presentation
The current report presents two cases of HLH with presentations different from each other and previously reported cases. Case 1 was a 15-month-old boy with fever, skin rash, splenomegaly, and bicytopenia, raised triglyceride levels, AST (aspartate transaminase), and ALT (alanine aminotransferase), normal ferritin, and abundant hemophagocytic cell in bone marrow aspiration. He was diagnosed with HLH and received HLH protocol as treatment. The patient had a homozygous intronic mutation; NM_199242: c.2448-13G > A in UNC13D. The associated disease was Familial Hemophagocytic Lymphohistiocytosis 3 (FHL3). Case 2, a 37-day-old female presented with fever, a history of neonatal cholestasis, and huge hepatosplenomegaly. Her whole-exome sequencing report manifested that the patient had the same mutation as case 1. Unfortunately, both patients passed away.

Conclusion
The sequencing of the entire UNC13D gene (coding and non-coding regions) is an applicable and valuable diagnostic procedure for the detection of deep intronic splicing variants and large inversions in patients with atypical manifestations of HLH (such as normal ferritin or triglyceride and cholesterol).