bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome
Authors: Raghuram Nikhil , Hasegawa Daisuke , Nakashima Kentaro , Rahman Syaza , Antoniou Evangelia , Skajaa Torjus , Merli Pietro , Verma Anupam , Rabin Karen R. , Aftandilian Catherine , Kotecha Rishi S. , Cheuk Daniel , Jahnukainen Kirsi , Kolenova Alexandra , Balwierz Walentyna , Norton Alice , O’Brien Maureen , Cellot Sonia , Chopek Ashley , Arad-Cohen Nira , Goemans Bianca , Rojas-Vasquez Marta , Ariffin Hany , Bartram Jack , Kolb E. Anders , Locatelli Franco , Klusmann Jan-Henning , Hasle Henrik , McGuire Bryan , Hasnain Afia , Sung Lillian , Hitzler Johann 
Published: February 2023

Abstract
Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for &gt; 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.
NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat
Authors: Wu Di , Zhu Jiansheng , You Lianghui , Wang Jingyu , Zhang Sufen , Liu Zhonghui , Xu Qu , Yuan Xiaojie , Yang Lei , Wang Wei , Tong Meiling , Hong Qin , Chi Xia 
Published: February 2023

Abstract
Background
Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities.

Methods
Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs.

Results
NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure.

Conclusions
Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Graphical abstract
Auxin efflux carrier ZmPIN1a modulates auxin reallocation involved in nitrate-mediated root formation
Authors: Wang Yubin , Xing Jiapeng , Wan Jiachi , Yao Qingqing , Zhang Yushi , Mi Guohua , Chen Limei , Li Zhaohu , Zhang Mingcai 
Published: February 2023

Abstract
Background
Auxin plays a crucial role in nitrate (NO3–)-mediated root architecture, and it is still unclear that if NO3– supply modulates auxin reallocation for regulating root formation in maize (Zea mays L.). This study was conducted to investigate the role of auxin efflux carrier ZmPIN1a in the root formation in response to NO3– supply.

Results
Low NO3– (LN) promoted primary root (PR) elongation, while repressed the development of lateral root primordia (LRP) and total root length. LN modulated auxin levels and polar transport and regulated the expression of auxin-responsive and -signaling genes in roots. Moreover, LN up-regulated the expression level of ZmPIN1a, and overexpression of ZmPIN1a enhanced IAA efflux and accumulation in PR tip, while repressed IAA accumulation in LRP initiation zone, which consequently induced LN-mediated PR elongation and LR inhibition. The inhibition rate of PR length, LRP density and number of ZmPIN1a-OE plants was higher than that of wild-type plants after auxin transport inhibitor NPA treatment under NN and LN conditions, and the degree of inhibition of root growth in ZmPIN1a-OE plants was more obvious under LN condition.

Conclusion
These findings suggest that ZmPIN1a was involved in modulating auxin levels and transport to alter NO3–-mediated root formation in maize.
Lung nodule pre-diagnosis and insertion path planning for chest CT images
Authors: Xie Rong-Li , Wang Yao , Zhao Yan-Na , Zhang Jun , Chen Guang-Biao , Fei Jian , Fu Zhuang 
Published: February 2023

AbstractMedical image processing has proven to be effective and feasible for assisting oncologists in diagnosing lung, thyroid, and other cancers, especially at early stage. However, there is no reliable method for the recognition, screening, classification, and detection of nodules, and even deep learning-based methods have limitations. In this study, we mainly explored the automatic pre-diagnosis of lung nodules with the aim of accurately identifying nodules in chest CT images, regardless of the benign and malignant nodules, and the insertion path planning of suspected malignant nodules, used for further diagnosis by robotic-based biopsy puncture. The overall process included lung parenchyma segmentation, classification and pre-diagnosis, 3-D reconstruction and path planning, and experimental verification. First, accurate lung parenchyma segmentation in chest CT images was achieved using digital image processing technologies, such as adaptive gray threshold, connected area labeling, and mathematical morphological boundary repair. Multi-feature weight assignment was then adopted to establish a multi-level classification criterion to complete the classification and pre-diagnosis of pulmonary nodules. Next, 3-D reconstruction of lung regions was performed using voxelization, and on its basis, a feasible local optimal insertion path with an insertion point could be found by avoiding sternums and/or key tissues in terms of the needle-inserting path. Finally, CT images of 900 patients from Lung Image Database Consortium and Image Database Resource Initiative were chosen to verify the validity of pulmonary nodule diagnosis. Our previously designed surgical robotic system and a custom thoracic model were used to validate the effectiveness of the insertion path. This work can not only assist doctors in completing the pre-diagnosis of pulmonary nodules but also provide a reference for clinical biopsy puncture of suspected malignant nodules considered by doctors.
Pharmacological and non-pharmacological interventions in management of peripheral venipuncture-related pain: a randomized clinical trial
Authors: Yu Zhuowen , Zhou Yiwen , Xu Xiaofeng , Lin Lili , Le Qian , Gu Ying 
Published: February 2023

AbstractBackgroundVenipuncture is a routine nursing procedure in the pediatric ward for blood collection and transfusion. However, this procedure can cause severe pain and distress if not adequately managed.MethodsChildren aged 3–16 years old were randomized into three groups: EMLA group, distraction group, and combined group. The primary outcome was children’s self-reported pain scored using the Wong-Baker FACES® Pain Rating Scale. The parents-reported and observer-reported pain were scored using the Revised Face, Legs, Activity, Cry and Consolability Scale, and children’s salivary cortisol levels, heart rate, percutaneous oxygen saturation, venipuncture duration and retaining time of IV cannulas were the secondary outcomes.ResultsA total of 299 children (167 male, 55.8%, median age 8.5) were enrolled: EMLA group (n = 103), distraction group(n = 96) and combined group(n = 100). There was no statistical difference in self-reported pain (P = 0.051), parent-reported pain (P = 0.072), and observer-reported pain (P = 0.906) among the three groups. All three interventions can decrease children’s pain during IV cannulations. Additionally, the distraction group's salivary cortisol levels were lower than the combined group(P = 0.013). Furthermore, no significant difference was observed in the heart rate(P = 0.844), percutaneous oxygen saturation (P = 0.438), venipuncture duration (p = 0.440) and retaining time of IV cannulas (p = 0.843) among the three groups.ConclusionsAll three groups responded with slight pain during the peripheral venipuncture procedure. Therefore, medical workers in pediatric settings can use the interventions appropriate for their medical resources and availability while involving parents and children’s preferences whenever possible.Trial registrationThis trial was registered onhttps://register.clinicaltrials.gov/(Gov.ID NCT04275336).
Clinical outcomes of pediatric osteomyelitis
Authors: Disch Kylie , Hill Deirdre A. , Snow Harry , Dehority Walter 
Published: February 2023

Abstract
Background
Osteomyelitis in children may produce severe sequelae. However, the frequency and distribution of such complications by type of osteomyelitis (chronic or acute) is not well described.

Methods
We searched the HealthFacts® database (containing medical information on 68 million individual patients in the United States) with 238 International Classification of Diseases (ICD) version 10 codes for acute osteomyelitis and chronic osteomyelitis appearing in 2015. Outcomes were recorded for each subject, including development of limb length discrepancies, pathologic fractures, mortality, and need for multiple surgeries or prolonged orthopedic care (one to two years following diagnosis). Gender, age and season of diagnosis were also assessed. Chi-square tests were used to compare differences between categorical variables, and t-tests between continuous variables.

Results
Eight hundred sixty-nine subjects were included (57.4% male). Children with chronic osteomyelitis were older than those with acute osteomyelitis (median 9.5 years vs 12.0, respectively, p = .0004). Diagnoses were more common in winter (p = .0003). Four subjects died while hospitalized during the study period (two with acute osteomyelitis, two with chronic osteomyelitis). Limb length discrepancies were rare and similarly distributed between infection types (≤ 1.3% of subjects, p = .83). Subjects with chronic osteomyeltis were more likely to require long-term orthopedic follow-up (14.0% vs. 4.8% for acute osteomyelitis, p < .0001), suffer from pathologic fractures (1.5% vs < 1.0%, p = .003) and to require multiple surgeries (46.0% vs. 29.3%, p = .04).

Conclusions
Though infrequent, serious outcomes from osteomyelitis are more common with chronic osteomyelitis than acute osteomyelitis.
The genotypic and phenotypic characteristics contributing to high virulence and antibiotics resistance in Escherichia coli O25-B2-ST131 in comparison to non- O25-B2-ST131
Authors: Shahbazi Razieh , Salmanzadeh-Ahrabi Siavosh , Aslani Mohammad Mehdi , Alebouyeh Masoud , Falahi Jamal , Nikbin Vajihe Sadat 
Published: February 2023

Abstract
Background
Escherichia coli serogroup O25b-sequence type 131 (E. coli O25-B2-ST131) is considered as multidrug-resistant and hypervirulent organism. There is lack of data about involvement of this pathogen in the children’s infection. In this study, the prevalence, and clonality, virulence capacity, and antibiotic resistance phenotype and genotype of E. coli O25-B2-ST131 compared with non-O25-B2-ST131 isolates were investigated in children with urinary tract infection in Tehran, Iran.

Methods
The E. coli isolates from urine samples were identified using conventional microbiological methods. Characterization of E. coli O25-B2-ST131 clone, antibiotic susceptibility, biofilm formation, ESBLs phenotype and genotype, serum resistance, hemolysis, hydrophobicity, and formation of curli fimbriae were done using conventional microbiological and molecular methods. Clonality of the isolates was done by rep-PCR typing.

Results
Among 120 E. coli isolates, the highest and lowest antibiotic resistance was detected against ampicillin (92, 76.6%) and imipenem 5, (4.1%), respectively. Sixty-eight (56.6%) isolates were ESBL-producing and 58 (48.3%) isolates were considered as multi-drug resistance (MDR). The prevalence of ESBL-producing and MDR isolates in O25-B2-ST131 strains was higher compared with the non-O25-B2-ST131 strains (p value < 0.05). O25-B2-ST131 strains showed significant correlation with serum resistance and biofilm formation. Amongst the resistance and virulence genes, the prevalence of iucD, kpsMTII, cnf1, vat, blaCTX-M-15, and blaSHV were significantly higher among O25-B2-ST131 isolates in comparison with non-O25-B2-ST131 isolates (p value < 0.05). Considering a ≥ 80% homology cut-off, fifteen different clusters of the isolates were shown with the same rep-PCR pattern.

Conclusions
Our results confirmed the involvement of MDR-ESBLs producing E. coli strain O25-B2-ST131 in the occurrence of UTIs among children. Source tracking and control measures seem to be necessary for containment of the spread of hypervirulent and resistance variants in children.
Relationships between training load, peak height velocity, muscle soreness and fatigue status in elite-level young soccer players: a competition season study
Authors: Nobari Hadi , Eken Özgür , Kamiş Okan , Oliveira Rafael , González Pablo Prieto , Aquino Rodrigo 
Published: February 2023

Abstract
Background
This study aimed to compare training load parameters, delayed onset muscle soreness (DOMS), and fatigue status between season periods (1st and 2nd halves) in U14 soccer players and to analyze the relationships between training load parameters based on season periods (1st and 2nd halves) with peak height velocity (PHV), DOMS, and fatigue status in under-14 (U14) young elite soccer players. Additionally, it was intended to analyze if fatigue, DOMS and PHV could explain training load parameters across the season.

Methods
Twenty U14 players that competed in the national league participated in this study. The players were monitored during the whole season (26 weeks), and evaluations were carried out at the end of the in-season. Anthropometric and body composition parameters and the maturity offset of each player were utilized to compute each player's age at PHV. Players reported their levels of DOMS and fatigue status using Hooper index questionnaires. The internal load was monitored using the rating of perceived exertion (RPE). Acute weekly internal load (AW), chronic weekly internal load (CW), acute: chronic workload ratio (ACWR), training monotony (TM), and training strain (TS) were also obtained.

Results
The main results showed that TM was higher in the 2nd half, while CW, AW and DOMS were higher in the 1st half of the season. Moreover, the main correlations showed a positive correlation between PHV and TS (2nd half of the season) and between fatigue and TM (1st half of the season).

Conclusion
In conclusion, variations in well-being status and PHV cannot explain the variations in internal training loads in elite U14 soccer players. In addition, internal training load indices during the first half of the competitive season can promote a fundamental base for progression loads during the second period of the competitive season.
Cognitive behavior therapy for diabetes distress, depression, health anxiety, quality of life and treatment adherence among patients with type-II diabetes mellitus: a randomized control trial
Authors: Abbas Qasir , Latif Sana , Ayaz Habib Hina , Shahzad Salman , Sarwar Uzma , Shahzadi Mafia , Ramzan Zoobia , Washdev Washdev 
Published: February 2023

AbstractObjectiveDiabetes distress typically causes depressive symptoms; common comorbidity of diabetes unpleasantly affects patients’ medical and psychological functions. Psychotherapeutic interventions are effective treatments to treat depressive symptoms and to improve the quality of life in many chronic diseases including diabetes. The present study investigated the efficacy of cognitive behavior therapy (CBT) to treat depressive symptoms in patients with type 2 diabetes mellitus (T2DM) using experimental and waitlist control conditions.Materials and MethodsA total of 130 diagnosed patients with T2DM were taken from outdoor patients services of different hospitals in Faisalabad. Ninety patients met the eligibility criteria and were randomly assigned to experimental (n = 45) and waitlist control (n = 45) conditions. All the patients completed clinical interviews and assessment measures at pre-and post-assessment stages (16 weeks intervals). Medical consultants at the respective hospitals diagnosed the patients on the base of their medical reports and then referred those patients to us. Then we used different scales to assess primary and secondary outcomes: Diabetes Distress Scale (DDS) and Patient Health Questionnaire (PHQ) to assess primary outcomes, and a Short Health Anxiety Inventory (SHAI), a Revised Version of the Diabetes Quality of Life Questionnaire (DQLQ), and a General Medication Adherence Scale (GMAS) were used to investigate secondary outcomes. Repeated measure ANOVA was used to analyze the results.ResultsThe findings indicated that patients who received CBT got a significant reduction in their diabetes distress F(1,60) = 222.710,P < 0.001, η2 = .788), depressive symptoms F(1,60) = 94.436,P < 0.001, η2 = .611), health anxiety F(1,60) = 201.915,P < .0.001, η2 = 771), and a significant improvement in their quality of life F(1,60) = 83.352,P < 0.001, η2 = .581), treatment adherence F(1,60) = 67.579,P < 0.001, η2 = .566) and physical activity schedule F(1,60) = 164.245, P < .0.001, η2 = .736 as compared to the patients in waitlist control condition.ConclusionIt is concluded that cognitive behavior therapy is an effective and promising intervention for depressive symptoms, diabetes distress, and health anxiety which also helps the person to promote quality of life, treatment adherence and physical activity.
Tinospora sinensis (Lour.) Merr alkaloid rich extract induces colon cancer cell death via ROS mediated, mTOR dependent apoptosis pathway: “an in-vitro study”
Authors: Badavenkatappa gari Sreelakshmi , Nelson Vinod K. , Peraman Ramalingam 
Published: February 2023

Abstract
Background
Colorectal cancer (CRC) is the second most mortality rate causing disease after lung cancer. Though there is a significant improvement in the treatment schedule offered to CRC. However, there is no notable decrease in terms of cases as well as death rate. Hence, there is an urgent need to discover novel cancer therapeutics to treat CRC. Since ancient times, the use of phytochemicals has drawn huge attention as chemo-preventive and chemotherapeutic agents. Earlier studies on Tinospora sinensis (TS) revealed the cytotoxic effect on human colorectal carcinoma (HCT-116) cells, yet the mechanism is to be uncovered. Therefore, the present study was designed to study the cell death mechanism of TS in HCT-116 cells.

Method
Different extracts such as n-hexane, ethyl acetate, and ethanol extracts from the root part of TS were prepared using a cold maceration process. The extracts were screened against cancer cell lines by methyl thiazoldiphenyltetrazolium bromide (MTT) assay. From the result, the most active extract was subjected to gas chromatography-mass spectrometry (GC-MS) and Fourier-Transform infrared spectroscopy (FTIR) analyses to identify the major constituents. Finally, the mechanism of cytotoxicity to cancer cells for the most active extract was evaluated using various experiments such as cell cycle analysis, Annexin-V assay, and Western blot.

Results
The results from the MTT assay indicated that the n-hexane extract of TS inhibits the growth of HCT-116 cells more effectively than other cancer cells like Henrietta Lacks cervical cancer cells (Hela), and Michigan cancer foundation-breast cancer (MCF-7). The GC-MS and FT-IR analyses revealed the presence of alkaloids in the n-hexane extract and were responsible for the apoptosis activity in HCT-cells via reactive oxygen species (ROS) generation, and phosphoinositide 3-kinase (PI3K)/ protein Kinase B (Akt)/ mammalian target of rapamycin (mTOR) down-regulation.

Conclusion
This study concludes that this finding is unique of its kind, and for the first time. The anticancer effect of TS root is specific to colon cancer cells (HCT-116). This distinctive finding helps the researchers to investigate further, and to identify a novel source for anti-colon cancer drug candidates in near future.
The mediating effect of critical thinking between interest in learning and caring among nursing students: a cross-sectional study
Authors: Tong Lai Kun , Au Mio Leng , Li Yue Yi , Ng Wai I. , Wang Si Chen 
Published: February 2023

Abstract
Background
Previous studies have explored the influence of interest in learning on caring and critical thinking, as well as the relationship between caring and critical thinking. However, the mediating effect of critical thinking in interest learning and caring among nursing students has not been clarified.

Methods
Nursing students who enrolled for the 2021/2022 academic year in diploma, undergraduate, or graduate programs in five provinces of China (Guangdong, Sichuan, Jiangsu, Hunan and Macao). An online survey with a convenience sampling method was employed to collect data. The questionnaires were administered to 692 participants between January 20 and 26, 2022. Amos 26.0 was employed to establish the structural equation modelling and analyze the mediating effect of critical thinking on interest in learning and caring.

Results
The first regression equation showed that interest in learning significantly influenced caring (β = 0.339, p <  0.001). The third regression equation showed that critical thinking significantly influenced caring (β = 0.494, p <  0.001). The effect of interest in learning on caring was less in the third equation than in the first equation (β = 0.154 vs β = 0.339), which indicates partial mediation. Furthermore, interest in learning had an indirect positive effect (β = 0.186, p <  0.001) on caring mediated by critical thinking, with 95% confidence interval of 0.142 to 0.233.

Conclusions
Critical thinking was a significant mediator of the relationship between interest in learning and caring. It is suggested that nursing colleges and instructors should take into account students’ interest in learning and critical thinking as potential intervention elements to enhance caring.