bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study
Authors: Roussel Murielle , Lauwers-Cances Valérie , Macro Margaret , Leleu Xavier , Royer Bruno , Hulin Cyrille , Karlin Lionel , Perrot Aurore , Touzeau Cyrille , Chrétien Marie-Lorraine , Rigaudeau Sophie , Dib Mamoun , Nicolas-Virelizier Emmanuelle , Escoffre-Barbe Martine , Belhadj Karim , Mariette Clara , Stoppa Anne-Marie , Araujo Carla , Doyen Chantal , Fontan Jean , Kolb Brigitte , Garderet Laurent , Brechignac Sabine , Malfuson Jean-Valère , Jaccard Arnaud , Lenain Pascal , Borel Cécile , Hebraud Benjamin , Benbrahim Omar , Dorvaux Véronique , Manier Salomon , Augeul-Meunier Karine , Vekemans Marie-Christiane , Randriamalala Edouard , Chaoui Driss , Caers Jo , Chaleteix Carine , Benboubker Lofti , Vincent Laure , Glaisner Sylvie , Zunic Patricia , Slama Borhane , Eveillard Jean-Richard , Humbrecht-Kraut Catherine , Morel Véronique , Mineur Philippe , Eisenmann Jean-Claude , Demarquette Hélène , Richez Valentine , Vignon Marguerite , Caillot Denis , Facon Thierry , Moreau Philippe , Colin Anne-Laurène , Olivier Pascale , Wuilleme Soraya , Avet-Loiseau Hervé , Corre Jill , Attal Michel 
Published: May 2022

Abstract
High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.
Risk assessment with low-pass whole-genome sequencing of cell-free DNA before CD19 CAR T-cell therapy for large B-cell lymphoma
Authors: Cherng Hua-Jay J. , Sun Ryan , Sugg Bryant , Irwin Russell , Yang Haopeng , Le Cao Cuong , Deng Qing , Fayad Luis , Fowler Nathan H. , Parmar Simrit , Steiner Raphael , Hagemeister Fredrick , Nair Ranjit , Lee Hun Ju , Rodriguez Maria , Samaniego Felipe , Iyer Swaminathan P. , Flowers Christopher R. , Wang Linghua , Nastoupil Loretta J. , Neelapu Sattva S. , Ahmed Sairah , Strati Paolo , Green Michael R. , Westin Jason 
Published: May 2022

AbstractPatients with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART19). However, more than half of recipients will experience treatment failure. Thus, approaches are needed to identify high-risk patients who may benefit from alternative or consolidative therapy. We evaluated low-pass whole-genome sequencing (lpWGS) of cell-free DNA (cfDNA) before CART19 as a new approach for risk stratification. We performed lpWGS on pretreatment plasma samples from 122 patients at time of leukapheresis who received standard-of-care CART19 for rrLBCL to define DNA copy number alterations (CNAs). In multivariable selection, high focal CNA score (FCS) denoting genomic instability was the most significant pretreatment variable associated with inferior 3-month complete response rates (28% vs 56%, P = .0029), progression-free survival (PFS; P = .0007; hazard ratio, 2.11), and overall survival (OS; P = .0026; hazard ratio, 2.10). We identified 34 unique focal CNAs in 108 (89%) patients; of these, deletion 10q23.3 leading to loss of FAS death receptor was the most highly associated with poor outcomes, leading to inferior PFS (P &lt; .0001; hazard ratio, 3.49) and OS (P = .0027; hazard ratio, 2.68). By combining FCS with traditional markers of increased tumor bulk (elevated lactate dehydrogenase and &gt;1 extranodal site), we built a simple risk model that could reliably risk stratify patients. Thus, lpWGS of cfDNA is a minimally invasive assay that could rapidly identify high-risk patients and may guide patient selection for and targeted therapies to evaluate in future clinical trials.
Gene silencing, knockout and over-expression of a transcription factor ABORTED MICROSPORES (SlAMS) strongly affects pollen viability in tomato (Solanum lycopersicum)
Authors: Bao Huihui , Ding Yumei , Yang Fei , Zhang Jie , Xie Junjun , Zhao Chongyan , Du Kanghua , Zeng Yawen , Zhao Kai , Li Zuosen , Yang Zhengan 
Published: May 2022

Abstract
Background
The tomato (Solanum lycopersicum L.) is an economically valuable crop grown worldwide. Because the use of sterile males reduces the cost of F1 seed production, the innovation of male sterility is of great significance for tomato breeding. The ABORTED MICROSPORES gene (AMS), which encodes for a basic helix-loop-helix (bHLH) transcription factor, has been previously indicated as an essential gene for tapetum development in Arabidopsis and rice. To determine the function of the SlAMS gene (AMS gene from S. lycopersicum) and verify whether it is a potential candidate gene for generating the male sterility in tomato, we used virus-induced gene silencing (VIGS), CRISPR/Cas9-mediated genome editing and over-expression technology to transform tomato via Agrobacterium infection.

Results
Here, the full-length SlAMS gene with 1806 bp from S. lycopersicum (Accession No. MK591950.1) was cloned from pollen cDNA. The results of pollen grains staining showed that, the non-viable pollen proportions of SlAMS-silenced (75%), −knockouted (89%) and -overexpressed plants (60%) were significantly higher than the wild type plants (less than 10%; P < 0.01). In three cases, the morphology of non-viable pollen grains appeared tetragonal, circular, atrophic, shriveled, or otherwise abnormally shaped, while those of wild type appeared oval and plump. Furthermore, the qRT-PCR analysis indicated that SlAMS in anthers of SlAMS-silenced and -knockouted plants had remarkably lower expression than in that of wild type (P < 0.01), and yet it had higher expression in SlAMS-overexpressed plants (P < 0.01).

Conclusion
In this paper, Our research suggested alternative approaches to generating male sterility in tomato, among which CRISPR/Cas9-mediated editing of SlAMS implied the best performance. We also demonstrated that the downregulation and upregulation of SlAMS both affected the pollen formation and notably led to reduction of pollen viability, suggesting SlAMS might be essential for regulating pollen development in tomato. These findings may facilitate studies on clarifying the SlAMS-associated molecular regulatory mechanism of pollen development in tomato.
The associations between low abundance of Mycoplasma hominis and female fecundability: a pregnancy-planning cohort study
Authors: Hong Xiang , Yin Jiechen , Wang Wei , Zhao Fanqi , Ding Xiaoling , Yu Hong , Zhang Xuening , Wang Bei 
Published: May 2022

Abstract
Objective
To explore the impact of pre-pregnancy vaginal Mycoplasma hominis (M. hominis) colonization of low abundance on female fecundability.

Methods
In total, 89 females participating in a pre-pregnancy health examination program were included, and their pregnancy outcomes were followed up for 1 year. Vaginal swabs were collected, 16S rRNA genes were sequenced, and M. hominis colonization was confirmed by qPCR. Cox models were used to estimate the fecundability odds ratio (FOR) for women with M. hominis.

Results
The prevalence of M. hominis was 22.47% (20/89), and the abundance was relatively low (the cycle thresholds of the qPCR were all more than 25). In terms of the vaginal microbiome, the Simpson index of the positive group was significantly lower than that of the negative group (P = 0.003), which means that the microbiome diversity appeared to increase with M. hominis positivity. The relative abundance of M. hominis was negatively correlated with Lactobacillus crispatus (rho = − 0.24, P = 0.024), but positively correlated with Gardnerella vaginalis, Atopobium vaginae and Prevotella bivia (P all < 0.05). The cumulative one-year pregnancy rate for the M. hominis positive group was lower than that in the negative group (58.96% vs 66.76%, log-rank test: P = 0.029). After controlling for potential confounders, the risk of pregnancy in the M. hominis positive group was reduced by 38% when compared with the positive group (FOR = 0.62, 95% CI: 0.42–0.93).

Conclusion
The vaginal colonization of M. hominis at a low level in pre-pregnant women is negatively correlated with female fecundability.
The association between fear of falling and occurrence of falls: a one-year cohort study
Authors: Asai Tsuyoshi , Oshima Kensuke , Fukumoto Yoshihiro , Yonezawa Yuri , Matsuo Asuka , Misu Shogo 
Published: May 2022

Abstract
Background
Both multiple fall experiences and fear of falling (FoF) would make people susceptible to another fall; however, the associations are unknown. This study investigates the association of FoF with fall occurrence among older adults according to their fall history.

Methods
In this study, we adopted a longitudinal observational design. We visited 20 community centers to recruit 1,025 older adults (aged 65 years or older). At baseline, FoF was assessed using a single-item questionnaire. The number of falls in the past year was obtained via a self-questionnaire and participants were classified into three fall history groups (0: non-faller, 1: single faller, 2 or more: multiple faller). After a year of following-up, the number of falls during the year was considered as the main outcome. Poisson regression models clarified the influence of FoF on fall occurrence during the one-year follow-up, according to the participants’ fall history.

Results
The final sample comprised 530 individuals (follow-up rate: 530/801, 66.4%). Fall history, FoF, and interaction between multiple fallers and FoF were significant in the adjusted statistical model (rate ratio [95% confidence interval]: single faller = 2.81 [1.06, 6.30], multiple faller = 13.60 [8.00, 23.04], FoF = 3.70 [2.48, 5.67], multiple faller*FoF = 0.37 [0.20, 0.68]).

Conclusions
We found that FoF was associated with the occurrence of falls in community-dwelling older adults. However, its association was lower in multiple fallers.
Construction and validation of a prognostic model of RNA binding proteins in clear cell renal carcinoma
Authors: Han Wenkai , Fan Bohao , Huang Yongsheng , Wang Xiongbao , Zhang Zhao , Gu Gangli , Liu Zhao 
Published: May 2022

Abstract
Background
The dysfunction of RNA binding proteins (RBPs) is associated with various inflammation and cancer. The occurrence and progression of tumors are closely related to the abnormal expression of RBPs. There are few studies on RBPs in clear cell renal carcinoma (ccRCC), which allows us to explore the role of RBPs in ccRCC.

Methods
We obtained the gene expression data and clinical data of ccRCC from the Cancer Genome Atlas (TCGA) database and extracted all the information of RBPs. We performed differential expression analysis of RBPs. Risk model were constructed based on the differentially expressed RBPs (DERBPs). The expression levels of model markers were examined by reverse transcription-quantitative PCR (RT-qPCR) and analyzed for model-clinical relevance. Finally, we mapped the model's nomograms to predict the 1, 3 and 5-year survival rates for ccRCC patients.

Results
The results showed that the five-year survival rate for the high-risk group was 40.2% (95% CI = 0.313 ~ 0.518), while the five-year survival rate for the low-risk group was 84.3% (95% CI = 0.767 ~ 0.926). The ROC curves (AUC = 0.748) also showed that our model had stable predictive power. Further RT-qPCR results were in accordance with our analysis (p < 0.05). The results of the independent prognostic analysis showed that the model could be an independent prognostic factor for ccRCC. The results of the correlation analysis also demonstrated the good predictive ability of the model.

Conclusion
In summary, the 4-RBPs (EZH2, RPL22L1, RNASE2, U2AF1L4) risk model could be used as a prognostic indicator of ccRCC. Our study provides a possibility for predicting the survival of ccRCC.
Peritoneal dialysis catheter salvage performed by nephrologists in tunnel exposure management
Authors: Kang Seok Hui , Kim A. Young , Do Jun Young 
Published: May 2022

Abstract
Background
Tunnel exposure, a non-infectious complication, is a rare finding in peritoneal dialysis (PD) patients, which has been described in some case reports. Our study aimed to present catheter salvage therapy using a revision procedure of tunnel exposure by nephrologists.

Methods
Our retrospective study was conducted between July 1998 and October 2021. We identified all PD patients with tunnel exposure from a database of a tertiary medical center. Tunnel exposure was diagnosed following gross inspection by clinicians during outpatient consultations. We attempted revision with partial external cuff shaving and creating a new tunnel without catheter change.

Results
Fourteen cases in 12 patients were diagnosed as tunnel exposure. The median age at presentation of tunnel exposure was 51 years. Eleven patients underwent revision, and the PD catheter was removed in one patient. The patients who underwent revision were followed up for 6 months. The catheter salvage rate was 72.7%.

Conclusions
The present study demonstrated that catheter revision performed by nephrologists could be a valuable alternative for original catheter salvage before considering catheter removal in tunnel exposure management.
Nomogram-based risk prediction of macrosomia: a case-control study
Authors: Du Jing , Zhang Xiaomei , Chai Sanbao , Zhao Xin , Sun Jianbin , Yuan Ning , Yu Xiaofeng , Zhang Qiaoling 
Published: May 2022

Abstract
Background
Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester.

Methods
A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia.

Results
The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18–3.83)/obesity (OR: 3.54, 95% CI: 1.56–8.04), multiparity (OR:1.88, 95% CI: 1.16–3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90–68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31–3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00–3.10) and TC (OR: 1.36, 95% CI: 1.00–1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755–0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively.

Conclusion
The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.
Leveraging artificial intelligence to predict ERG gene fusion status in prostate cancer
Authors: Dadhania Vipulkumar , Gonzalez Daniel , Yousif Mustafa , Cheng Jerome , Morgan Todd M. , Spratt Daniel E. , Reichert Zachery R. , Mannan Rahul , Wang Xiaoming , Chinnaiyan Anya , Cao Xuhong , Dhanasekaran Saravana M. , Chinnaiyan Arul M. , Pantanowitz Liron , Mehra Rohit 
Published: May 2022

Abstract
Background
TMPRSS2-ERG gene rearrangement, the most common E26 transformation specific (ETS) gene fusion within prostate cancer, is known to contribute to the pathogenesis of this disease and carries diagnostic annotations for prostate cancer patients clinically. The ERG rearrangement status in prostatic adenocarcinoma currently cannot be reliably identified from histologic features on H&E-stained slides alone and hence requires ancillary studies such as immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or next generation sequencing (NGS) for identification.

Methods

Objective
We accordingly sought to develop a deep learning-based algorithm to identify ERG rearrangement status in prostatic adenocarcinoma based on digitized slides of H&E morphology alone.

Design
Setting, and Participants: Whole slide images from 392 in-house and TCGA cases were employed and annotated using QuPath. Image patches of 224 × 224 pixel were exported at 10 ×, 20 ×, and 40 × for input into a deep learning model based on MobileNetV2 convolutional neural network architecture pre-trained on ImageNet. A separate model was trained for each magnification. Training and test datasets consisted of 261 cases and 131 cases, respectively. The output of the model included a prediction of ERG-positive (ERG rearranged) or ERG-negative (ERG not rearranged) status for each input patch.
Outcome measurements and statistical analysis: Various accuracy measurements including area under the curve (AUC) of the receiver operating characteristic (ROC) curves were used to evaluate the deep learning model.

Results and Limitations
All models showed similar ROC curves with AUC results ranging between 0.82 and 0.85. The sensitivity and specificity of these models were 75.0% and 83.1% (20 × model), respectively.

Conclusions
A deep learning-based model can successfully predict ERG rearrangement status in the majority of prostatic adenocarcinomas utilizing only H&E-stained digital slides. Such an artificial intelligence-based model can eliminate the need for using extra tumor tissue to perform ancillary studies in order to assess for ERG gene rearrangement in prostatic adenocarcinoma.
Neonatal bilateral adrenal hemorrhage and adrenal insufficiency accompanied by Subgaleal hematoma: a case report with brief review of literature
Authors: Esslami Golnaz Ghazizadeh , Moienafshar Atousa 
Published: May 2022

AbstractBackgroundNeonatal adrenal hemorrhage (NAH) is an almost infrequent phenomenon (0.2–0.55%). Mechanical compression and alterations of venous pressure during delivery are considered the most probable explanations. Approximately 10% of the cases might have bilateral involvement. Clinical symptoms include abdominal mass, poor feeding, vomiting, prolonged jaundice, and anemia. Subgaleal hemorrhage (SGH) is one of the most clinically remarkable and potentially hazardous postnatal cranial injuries.Case presentationAn early-term Iranian male neonate who was born through spontaneous vaginal delivery and experienced shoulder dystocia was diagnosed with bilateral NAH leading to adrenal insufficiency requiring glucocorticoid and mineralocorticoid supplementation. The SGH and jaundice were other postnatal complications. Serial monthly abdominal and brain ultrasound revealed complete regression of lesions after 70 days. However, after 16 months, the neonate has been still treated with hydrocortisone and fludrocortisone for the adrenal insufficiency diagnosis. He has a lower limit weight for age; however, developmental milestones have been appropriate for age.Discussion and conclusionAdrenal hemorrhage and SGH should be examined and looked for, particularly with proven evidence of difficult delivery and asphyxia in at-risk newborns. Clinical and ultrasound follow-up is mandatory for the assessment of hemorrhage resolution and conservative management. The early detection and treatment of adrenal insufficiency by laboratory examination is strongly recommended in bilateral cases. Furthermore, the early recognition of postnatal SGH to prevent clinical and neurological outcomes seems essential.
Pain and pain management in children and adolescents receiving hospital care: a cross-sectional study from Sweden
Authors: Andersson Viveka , Bergman Stefan , Henoch Ingela , Simonsson Hanna , Ahlberg Karin 
Published: May 2022

Abstract
Background
Pain is a common symptom in children receiving hospital care. Adequate pain management in paediatric patients is of the utmost importance. Few studies have investigated children’s own experiences of pain during hospitalization.

Aim
To describe the prevalence of pain, self-reported pain intensity at rest and during movement, pain management and compliance with pain treatment guidelines in children and adolescents receiving hospital care. Furthermore, to examine self-reported statements about pain relief and how often staff asked about pain.

Methods
A quantitative, cross-sectional study with descriptive statistics as the data analysis method was conducted at a county hospital in western Sweden. Sixty-nine children/adolescents aged 6–18 years who had experienced pain during their hospital stay were included. A structured, verbally administered questionnaire was used to obtain pain reports. The participants were also asked what they considered alleviated pain and how often they told staff about pain. Patient demographics, prescribed analgesics and documentation of pain rating were obtained from medical records.

Results
Fifty children/adolescents (72%) experienced moderate to severe pain in the previous 24 hours. At the time of the interview 36% reported moderate to severe pain at rest and 58% during movement. Seven participants (10%) reported severe pain both at rest and during movement. About one-third were on a regular multimodal analgesic regimen and 28% had used a validated pain rating scale. Thirty children/adolescents (43%) reported that they had experienced procedural pain in addition to their underlying pain condition. Most of the children/adolescents (74%) reported that analgesics provided pain relief. Forty (58%) stated that various non-pharmacological methods were helpful.

Conclusions
Despite evidence-based guidelines, half of the children/adolescents experienced moderate to severe pain, highlighting the need for improvement. Pain levels should be assessed both at rest and during movement. Response to treatment should be evaluated to prevent undertreatment of pain. Compliance with guidelines and professional communication are of the utmost importance for pain management in children/adolescents. Non-pharmacological methods are a valuable part of a pain management strategy. This study shows that it is important to evaluate and improve pain care also outside specialised tertiary clinics.