bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of clonal immunoglobulin heavy V-D-J gene rearrangements in Chinese patients with chronic lymphocytic leukemia: Clinical features and molecular profiles
Authors: Deng Xinyue , Zhang Meilan , Wang Jiachen , Zhou Xiaoxi , Xiao Min 
Published: February 2023

IntroductionSeveral prognostic factors of chronic lymphocytic leukemia (CLL) have been identified, such as cytogenetic aberrations and recurrent gene mutations. B-cell receptor (BCR) signaling plays an important role in the tumorigenesis of CLL, and its clinical significance in predicting prognosis is also under study.MethodsTherefore, we assessed the already-known prognostic markers, immunoglobulin heavy chain (IGH) gene usage and the associations among these factors in 71 patients diagnosed with CLL in our center from October 2017 to March 2022. Sequencing of IGH gene rearrangements was performed using Sanger sequencing or IGH-based next-generation sequencing, and the results were further analyzed for distinct IGH/IGHD/IGHJ genes and the mutational status of the clonotypic IGHV (IGH variable) gene.ResultsIn summary, by analyzing the distribution of potential prognostic factors in CLL patients, we displayed a landscape of molecular profiles, confirmed the predictive value of recurrent genetic mutations and chromosome aberrations, and found that IGHJ3 was associated with favorable markers (mutated IGHV, trisomy 12), while IGHJ6 tended to correlate with unfavorable factors (unmutated IGHV, del17p).DiscussionThese results provided an indication for IGH gene sequencing in predicting the prognosis of CLL.
Sub-Tenon's bupivacaine injection is superior to placebo for pediatric strabismus surgery: A meta-analysis
Authors: Weijuan Zeng , Zonghuan Li , Qian Wang , Xizhi Deng , Bin Jiang , Min Ke 
Published: February 2023

BackgroundThe effect of post-operation sub-Tenon's bupivacaine injection for pediatric strabismus surgery is controversial. The objective of this meta-analysis is to compare the outcome of sub-Tenon injection of bupivacaine and placebo duringstrabismus surgery.MethodsWe searched the databases (Pubmed, Cochrane library and EMBASE) and reference lists systematically. Randomized controlled trials (RCTs) comparing sub-Tenon's bupivacaine and placebo injection for pediatric strabismus surgery were included. The methodological quality was evaluated by the Cochrane risk of bias (ROB) tool. Outcome measurements were pain score, oculocardiac reflex (OCR), additional drug consumption and related complications. RevMan 5.4 was used for the statistical analysis and graph preparation. For the outcomes that are not suitable for statistical analysis, descriptive analysis was performed.ResultsA total of 5 RCTs with 217 patients were finally identified and analyzed. Sub-Tenon's bupivacaine injection showed pain relief within 30 min after operation. But with the extension of time, the analgesic effect gradually disappeared at 1 h. It can reduce the incidence of OCR, vomiting and supplementary drug requirements. However, in terms of nausea, there is no difference between the two groups.ConclusionSub-Tenon's bupivacaine injection can relieve short-term postoperative pain, reduce the incidence of OCR and vomiting, and reduce the use of supplementary drugs in strabismus surgery.
Autoimmunity associates with severity of illness in elderly patients with drug-induced liver injury
Authors: Xiong Yu-Ting , Wang Jian-Fei , Niu Xiao-Xia , Fu Yi-Ming , Wang Ke-Xin , Wang Chun-Yan , Li Qian-Qian , Wang Jian-Jun , Zhao Jun , Ji Dong 
Published: February 2023

Background: Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI.Methods: In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level &gt;1.1 × ULN (1826 mg/dL), or high titer (&gt;1:80) of ANA, or SMA.Results: In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0–66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991–0.997; p &lt; 0.001), AST (OR: 1.001, 95% CI: 1.000–1.003, p = 0.012), TBIL (OR: 1.006, 95% CI: 1.003–1.010, p &lt; 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258–2.672, p = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986–0.993, p &lt; 0.001), TBIL (OR: 1.004, 95% CI: 1.000–1.007, p = 0.028), age (OR: 1.123, 95% CI: 1.067–1.183, p &lt; 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191–2.608, p = 0.005) were associated with the stage of hepatic fibrosis.Conclusion: This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.
Predicting treatment response to vancomycin using bacterial DNA load as a pharmacodynamic marker in premature and very low birth weight neonates: A population PKPD study
Authors: Samb Amadou , De Kroon Rimke , Dijkstra Koos , Van Den Brand Marre , Bos Martine , Van Den Dungen Frank , Veldkamp Agnes , Wilhelm Bram , De Haan Timo R. , Bijleveld Yuma A. , Tutu Van Furth Marceline , Savelkoul Paul , Swart Noortje , Mathot Ron , Van Weissenbruch Mirjam 
Published: February 2023

Background: While positive blood cultures are the gold standard for late-onset sepsis (LOS) diagnosis in premature and very low birth weight (VLBW) newborns, these results can take days, and early markers of possible treatment efficacy are lacking. The objective of the present study was to investigate whether the response to vancomycin could be quantified using bacterial DNA loads (BDLs) determined by real-time quantitative polymerase chain reaction (RT-qPCR).Methods: VLBW and premature neonates with suspected LOS were included in a prospective observational study. Serial blood samples were collected to measure BDL and vancomycin concentrations. BDLs were measured with RT-qPCR, whereas vancomycin concentrations were measured by LC-MS/MS. Population pharmacokinetic–pharmacodynamic modeling was performed with NONMEM.Results: Twenty-eight patients with LOS treated with vancomycin were included. A one-compartment model with post-menstrual age (PMA) and weight as covariates was used to describe the time PK profile of vancomycin concentrations. In 16 of these patients, time profiles of BDL could be described with a pharmacodynamic turnover model. The relationship between vancomycin concentration and first-order BDL elimination was described with a linear-effect model. Slope S increased with increasing PMA. In 12 patients, no decrease in BDL over time was observed, which corresponded with clinical non-response.Discussion: BDLs determined through RT-qPCR were adequately described with the developed population PKPD model, and treatment response to vancomycin using BDL in LOS can be assessed as early as 8 h after treatment initiation.
S-Ketamine attenuates inflammatory effect and modulates the immune response in patients undergoing modified radical mastectomy: A prospective randomized controlled trial
Authors: Zhang Junxia , Ma Qian , Li Wenbin , Li Xiaohui , Chen Xuexin 
Published: February 2023

Objective: This study aimed to investigate the impact of varying dosages of S-ketamine on perioperative immune-inflammatory responses in patients undergoing modified radical mastectomy (MRM).Methods: This is a prospective, randomized, controlled trial. A total of 136 patients with American Society of Anesthesiologists status I/II scheduled for MRM were enrolled and randomly assigned into groups to receive the control (C) or one of three different doses [0.25 (L-Sk), 0.5 (M-Sk), or 0.75 (H-Sk) mg/kg] of S-ketamine. The primary outcomes were the cellular immune function and inflammatory factors before anesthesia and at the end of (T1) and 24 h (T2) after the surgery. Secondary outcomes included the visual analog scale (VAS) score, opioid consumption, rate of remedial analgesia, adverse events, and patient satisfaction.Results: The percentage and absolute counts of CD3+ and CD4+ cells in groups L-Sk, M-Sk, and H-Sk were higher than those of group C at T1 and T2. Moreover, a pairwise comparison revealed that the percentage in group H-Sk was higher than those in the L-Sk and M-Sk groups (p &lt; 0.05). The ratio of CD4+/CD8+ was lower in group C at T1 and T2 than those in groups M-Sk and H-Sk (p &lt; 0.05). There was no significant difference in the percentage and absolute counts of natural killer (NK) cells and B lymphocytes among the four groups. However, compared with group C, the concentrations of white blood cells (WBC), neutrophils (NEUT), hypersensitive C-reactive protein (hs-CRP), the neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) at T1 and T2 in three different doses of S-ketamine groups were significantly low, and the lymphocytes were significantly high. The ratio of SIRI and NLR at T2 in group M-Sk was lower than that in group L-Sk (p &lt; 0.05). Additionally, a significant decrease in VAS score, opioid consumption, rates of remedial analgesia, and adverse events was observed in the M-Sk and H-Sk groups.Conclusion: Collectively, our study demonstrates that S-ketamine could reduce opioid consumption, decrease postoperative pain intensity, exert a systemic anti-inflammatory effect, and attenuate immunosuppression in patients undergoing MRM. Moreover, we found that the effects of S-ketamine are related to the dose used, with significant differences observed in 0.5 or 0.75 mg/kg of S-ketamine.Clinical Trial Registration:chictr.org.cn, identifier ChiCTR2200057226.
Rapid post-eruptive maturation of porcine enamel
Authors: Depalle Baptiste , Karaaslan Hakan , Obtel Nicolas , Gil-Bona Ana , Teichmann Maren , Mascarin Gabrielle , Pugach-Gordon Megan , Bidlack Felicitas B. 
Published: February 2023

The teeth of humans and pigs are similar in size, shape, and enamel thickness. While the formation of human primary incisor crowns takes about 8 months, domestic pigs form their teeth within a much shorter time. Piglets are born after 115 days of gestation with some of their teeth erupted that must after weaning meet the mechanical demands of their omnivorous diet without failure. We asked whether this short mineralization time before tooth eruption is combined with a post-eruptive mineralization process, how fast this process occurs, and how much the enamel hardens after eruption. To address this question, we investigated the properties of porcine teeth at two, four, and sixteen weeks after birth (N = 3 animals per time point) through analyses of composition, microstructure, and microhardness. We collected data at three standardized horizontal planes across the tooth crown to determine the change of properties throughout the enamel thickness and in relation to soft tissue eruption. Our findings indicate that porcine teeth erupt hypomineralized compared to healthy human enamel and reach a hardness that is similar to healthy human enamel within less than 4 weeks.
Physiological analysis reveals the mechanism of accelerated growth recovery for rice seedlings by nitrogen application after low temperature stress
Authors: Wang Hui , Zhong Lei , Fu Xiaoquan , Huang Shiying , Zhao Desheng , He Haohua , Chen Xiaorong 
Published: February 2023

Low temperature and overcast rain are harmful to directly seeding early rice, it can hinder rice growth and lower rice biomass during the seedling stage, which in turn lowers rice yield. Farmers usually use N to help rice recuperate after stress and minimize losses. However, the effect of N application on the growth recovery for rice seedlings after such low temperature stress and its associated physiological changes remain unclearly. Two temperature settings and four post-stress N application levels were used in a bucket experiment to compare B116 (strong growth recovery after stress) with B144 (weak growth recovery). The results showed that the stress (average daily temperature at 12°C for 4 days) inhibited the growth of rice seedlings. Compared to the zero N group, the N application group’s seedling height, fresh weight and dry weight significantly increased after 12 days. In particular, the increases in all three growth indicators were relatively higher than that of N application at normal temperature, indicating the importance of N application to rice seedlings after low temperature stress. The antioxidant enzyme activity of rice seedlings increased significantly after N application, which reduced the damaging effect of ROS (reactive oxygen species) to rice seedlings. At the same time, the soluble protein content of seedlings showed a slow decrease, while the H2O2 and MDA (malondialdehyde) content decreased significantly. Nitrogen could also promote nitrogen uptake and utilization by increasing the expression of genes related to NH4+ and NO3− uptake and transport, as well as improving the activity of NR (nitrate reductase) and GS (glutamine synthetase) in rice. N could affect GA3 (gibberellin A3) and ABA (abscisic acid) levels by regulating the anabolism of GA3 and ABA. The N application group maintained high ABA levels as well as low GA3 levels from day 0 to day 6, and high GA3 levels as well as low ABA levels from day 6 to day 12. The two rice varieties showed obvious characteristics of accelerated growth recovery and positive physiological changes by nitrogen application after stress, while B116 generally showed more obvious growth recovery and stronger growth-related physiological reaction than that of B144. The N application of 40 kg hm-2 was more conducive to the rapid recovery of rice growth after stress. The above results indicated that appropriate N application promoted rice seedling growth recovery after low temperature stress mainly by increasing the activities of antioxidant enzymes and nitrogen metabolizing enzymes as well as regulating the levels of GA3 and ABA. The results of this study will provide a reference for the regulation of N on the recovery of rice seedling growth after low temperature and weak light stress.
Behavioral inflexibility in fragile X syndrome: Accounts from caregivers and self-advocates
Authors: Jones Angelina , Kang Sungeun , Shaffer Rebecca C. , Erickson Craig A. , Schmitt Lauren M. 
Published: February 2023

IntroductionBehavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one’s behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions. In addition to the individual and family impact, behavioral inflexibility is often recognized as a defining phenotype of FXS and appears to be specific to FXS when compared to other genetic forms of intellectual disability. Despite the pervasiveness and severity of behavioral inflexibility in FXS, there are limited measures that adequately assess behavioral inflexibility in FXS.MethodsWe conducted semi-structured virtual focus groups with 22 caregivers, 3 self-advocates, and 1 professional to gather key stakeholders’ perspectives on and experiences of inflexible behavior observed in FXS. Audio-recordings from focus groups were transcribed using NVivo, then verified and coded. Two trained professionals reviewed codes to extract primary themes.ResultsSix themes were extracted: (1) Intolerance of change, (2) Intolerance to uncertainty, (3) Repetitive interests and behaviors, (4) Family impact, (5) Change in behavior across the lifespan, and (6) Impact of the COVID pandemic. Our findings show common examples of these themes included intolerance to disruption to routine, perseverative questioning, watching the same things over and over, and caregivers having to extensively pre-plan for events.DiscussionThe purpose of the current study was to gain key stakeholders’ perspectives via focus groups to elicit information and understand patterns of inflexible behaviors in FXS, with the goal of developing a disorder-specific measure to accurately assess behavioral inflexibility across the lifespan and in response to treatment. We were able to capture several phenotypic examples of behavioral inflexibility in FXS as well as their impact on individuals with FXS and their families. The wealth of information gained through our study will aid in our next steps of item generation for measure development of Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability – Fragile X Syndrome (RIGID-FX).
Aberrant degree centrality of functional brain networks in subclinical depression and major depressive disorder
Authors: Yang Lei , Jin Chaoyang , Qi Shouliang , Teng Yueyang , Li Chen , Yao Yudong , Ruan Xiuhang , Wei Xinhua 
Published: February 2023

BackgroundAs one of the most common diseases, major depressive disorder (MDD) has a significant adverse impact on the li of patients. As a mild form of depression, subclinical depression (SD) serves as an indicator of progression to MDD. This study analyzed the degree centrality (DC) for MDD, SD, and healthy control (HC) groups and identified the brain regions with DC alterations.MethodsThe experimental data were composed of resting-state functional magnetic resonance imaging (rs-fMRI) from 40 HCs, 40 MDD subjects, and 34 SD subjects. After conducting a one-way analysis of variance, two-sample t-tests were used for further analysis to explore the brain regions with changed DC. Receiver operating characteristic (ROC) curve analysis of single index and composite index features was performed to analyze the distinguishable ability of important brain regions.ResultsFor the comparison of MDD vs. HC, increased DC was found in the right superior temporal gyrus (STG) and right inferior parietal lobule (IPL) in the MDD group. For SD vs. HC, the SD group showed a higher DC in the right STG and the right middle temporal gyrus (MTG), and a smaller DC in the left IPL. For MDD vs. SD, increased DC in the right middle frontal gyrus (MFG), right IPL, and left IPL, and decreased DC in the right STG and right MTG was found in the MDD group. With an area under the ROC (AUC) of 0.779, the right STG could differentiate MDD patients from HCs and, with an AUC of 0.704, the right MTG could differentiate MDD patients from SD patients. The three composite indexes had good discriminative ability in each pairwise comparison, with AUCs of 0.803, 0.751, and 0.814 for MDD vs. HC, SD vs. HC, and MDD vs. SD, respectively.ConclusionAltered DC in the STG, MTG, IPL, and MFG were identified in depression groups. The DC values of these altered regions and their combinations presented good discriminative ability between HC, SD, and MDD. These findings could help to find effective biomarkers and reveal the potential mechanisms of depression.
Participatory evaluation of municipal obesity prevention clubs in Tehran city: Strengths, challenges, and future direction
Authors: Edalati Sareh , Omidvar Nasrin , Takian Amirhossein , Rasam Farzaneh , Ghodsi Delaram , Majdzadeh Reza 
Published: February 2023

Background and aimCommunity-based initiatives are important for obesity prevention. This study aimed to evaluate the activities of municipal obesity prevention clubs (OBCs) in Tehran, Iran, using a participatory approach.MethodsThe evaluation team was formed, and the members identified the OBC's strengths, and challenges and provided suggestions for change through a participatory workshop, observation, focus group discussions, reviewing relevant documents (n = 97), and 35 interviews with involved stakeholders. The MAXQDA software was used for data analysis.ResultsAn empowerment training program for volunteers was identified as one of the strengths of OBCs. Despite the obesity prevention efforts of OBCs through public exercise sessions, healthy food festivals, and educational sessions, several challenges were identified that hinder participation in OBCs. These challenges included poor marketing strategies, poor training approaches in participatory planning, insufficient motivational support for volunteers, low perceived recognition of volunteers by the community, volunteers' low food and nutrition literacy, poor educational services in the communities, and limited funding for health promotion activities.ConclusionWeaknesses in all stages of community participation, including information, consultation, collaboration, and empowerment, in OBCs were detected. Facilitating a more enabling environment for informing and involving citizens, expanding neighborhood social capital, and involving health volunteers, academia, and all potential governmental sectors to collaborate for obesity prevention is recommended.