bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional associations of white matter integrity and neurological, post-traumatic stress disorder and autonomic symptoms in Veterans with and without history of loss of consciousness in mild TBI
Authors: Waters Abigail B. , Bottari Sarah A. , Jones Laura C. , Lamb Damon G. , Lewis Gregory F. , Williamson John B. 
Published: January 2024

BackgroundPosttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) share overlapping symptom presentations and are highly comorbid conditions among Veteran populations. Despite elevated presentations of PTSD after mTBI, mechanisms linking the two are unclear, although both have been associated with alterations in white matter and disruptions in autonomic regulation. The present study aimed to determine if there is regional variability in white matter correlates of symptom severity and autonomic functioning in a mixed sample of Veterans with and without PTSD and/or mTBI (N = 77).MethodsDiffusion-weighted images were processed to extract fractional anisotropy (FA) values for major white matter structures. The PTSD Checklist-Military version (PCL-M) and Neurobehavioral Symptom Inventory (NSI) were used to determine symptom domains within PTSD and mTBI. Autonomic function was assessed using continuous blood pressure and respiratory sinus arrythmia during a static, standing angle positional test. Mixed-effect models were used to assess the regional specificity of associations between symptom severity and white matter, with FA, global symptom severity (score), and white matter tract (tract) as predictors. Additional interaction terms of symptom domain (i.e., NSI and PCL-M subscales) and loss of consciousness (LoC) were added to evaluate potential moderating effects. A parallel analysis was conducted to explore concordance with autonomic functioning.ResultsResults from the two-way Score × Tract interaction suggested that global symptom severity was associated with FA in the cingulum angular bundle (positive) and uncinate fasciculus (negative) only, without variability by symptom domain. We also found regional specificity in the relationship between FA and autonomic function, such that FA was positively associated with autonomic function in all tracts except the cingulum angular bundle. History of LoC moderated the association for both global symptom severity and autonomic function.ConclusionsOur findings are consistent with previous literature suggesting that there is significant overlap in the symptom presentation in TBI and PTSD, and white matter variability associated with LoC in mTBI may be associated with increased PTSD-spectra symptoms. Further research on treatment response in patients with both mTBI history and PTSD incorporating imaging and autonomic assessment may be valuable in understanding the role of brain injury in treatment outcomes and inform treatment design.
Association between lifestyle and dietary preference factors and conventional adenomas and serrated polyps
Authors: Xu Jue , Chi Peihan , Qin Kang , Li Biao , Cheng Zhongxue , Yu Zhecong , Jiang Caixia , Yu Yunxian 
Published: January 2024

IntroductionBoth conventional adenoma (AD) and serrated polyp (SP) were known precursor lesions of colorectal cancer (CRC). Modifiable lifestyle factors were significantly associated with CRC risk, but whether these factors were related to the risk of different precursors of CRC needed to be clarified. This study aimed to evaluate the risks of AD and SP caused by lifestyle factors and compare the risk differences between AD and SP.MethodsThe study population was from the CRC screening cohort in Hangzhou, China. A total of 458,457 eligible individuals volunteered to undergo initial screening including the fecal immunochemical test (FIT) and the CRC risk assessment. Finally, 13,993 participants who had undergone colonoscopy tests and had been diagnosed at designated hospitals were selected in this study. All participants were required to fill out a questionnaire during the initial screening for collecting their information. The generalized estimate equation (GEE) model was used to assess the association between lifestyle factors/dietary preferences and AD/SP.ResultsThe body mass index (BMI) and smoking were positively associated with the risks of only SP (BMI: OR = 1.50, 95%CI: 1.23–1.84; smoking: OR = 1.29, 95%CI: 1.07–1.55), only AD (BMI: OR = 1.53, 95%CI: 1.28–1.82; OR = 1.24, 95%CI: 1.11–1.39), and synchronous SP and AD (BMI: OR = 1.97, 95%CI: 1.40–2.75; smoking: OR = 1.53, 95%CI: 1.27–1.85). In the case-group comparison, smoking was more strongly associated with the risk of synchronous SP and AD than only AD. Alcohol drinking was positively associated with the risk of AD (OR = 1.28, 95%CI: 1.14–1.44), but no statistically significant difference was observed in risks in the case-group comparison. Furthermore, whole-grain intake was associated with a decreased risk of only AD (OR = 0.78, 95%CI: 0.65–0.93). However, white meat intake was positively associated with risks of only SP when compared with AD cases (OR = 1.60, 95%CI: 1.15–2.23).ConclusionThe current study identified common risk factors such as BMI and smoking as well as different risks of certain factors (e.g., alcohol drinking and whole-grain intake) for SP and AD. However, there were still some factors, especially diet-related factors, that have not been fully elucidated in their association with the two lesions. Further research is needed in future to confirm and develop prevention strategies for different lesions.
Gut microbiota dysbiosis and protein energy wasting in patients on hemodialysis: an observational longitudinal study
Authors: Bi Xiao , Liu Yuqing , Yao Lu , Ling Lilu , Lu Jianxin , Hu Chun , Ding Wei 
Published: January 2024

BackgroundProtein energy wasting (PEW) is common in patients on hemodialysis, and its development may involve gut microbial dysbiosis. However, the exact relationship between the composition of different flora and the development of PEW remains unclear.MethodsThis is an observational longitudinal study on 115 patients undergoing hemodialysis who were followed up for 1 year. All the patients were evaluated at baseline, and different microbiota compositions were determined. After a 1 year follow-up period, the correlations between clinical parameter variations and the relative abundance of different gut flora were assessed using Spearman correlation. Moreover, the associations of the abundance of different gut microbiota with decrease in lean tissue mass and the development of PEW were analyzed using ROC curve and logistical regression analyses.ResultsWe found that the relative abundances of Actinobacteria and Bifidobacteriaceae were significantly lower in patients with PEW than in those who did not develop PEW (p &lt; 0.05). The abundance of Actinobacteria and Bifidobacteriaceae correlated positively with variations in serum albumin levels (r = 0.213, p = 0.035 and r = 0.214, p = 0.034, respectively), lean tissue mass (r = 0.296, p = 0.007 and r = 0.238, p = 0.002, respectively), and lean tissue index (r = 0.377, p &lt; 0.001 and r = 0.419, p &lt; 0.001, respectively). The area under the ROC curve or AUC values of Actinobacteria and Bifidobacteriaceae for the prediction of lean tissue mass decrease ranged from 0.676 to 0.708 (p &lt; 0.05). Thus, decrease in the abundance of Actinobacteria and Bifidobacteriaceae may be associated with decrease in lean tissue mass and the occurrence of PEW.ConclusionThe present findings imply Actinobacteria and Bifidobacteriaceae may be potential markers for predicting skeletal muscle mass decrease and PEW development in patients on hemodialysis.
RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2-positive locally advanced muscle-invasive urothelial bladder cancer: a multi-center phase Ib/II study (HOPE-03)
Authors: Wen Feng , Lin Tianhai , Zhang Peng , Shen Yali 
Published: January 2024

BackgroundBladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population.MethodsHOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life.DiscussionThe HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=137111, identifier ChiCTR2200060153.
Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19
Authors: Tschirhart Brent J. , Lu Xiangru , Mokale Kognou Aristide Laurel , Martin Claudio M. , Slessarev Marat , Fraser Douglas D. , Leligdowicz Aleksandra , Urquhart Bradley , Feng Qingping 
Published: January 2024

Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19.Methods: This was a pilot randomized, double-blind, placebo-controlled trial. Severe COVID-19 patients were randomly assigned to receive intravenous 50 μg/kg (low dose, n = 3), 100 μg/kg (high dose, n = 5) of SY-005 or placebo (n = 5) every 12 h for 7 days. Plasma SY-005 levels were assessed using enzyme-linked immunosorbent assay (ELISA) and the PK parameters were determined using non-compartmental analysis.Results: All patients treated with SY-005 had a normal baseline estimated glomerular filtration rate (eGFR, 104–125 mL/min/1.73 m2). Both low and high doses of SY-005 were cleared within 6 h after intravenous administration. Plasma maximum concentrations (Cmax), half-life, clearance and volume distribution of low and high doses of SY-005 were 402.4 and 848.9 ng/mL, 0.92 and 0.96 h, 7.52 and 15.19 L/h, and 9.98 and 20.79 L, respectively. Daily pre-dose circulating annexin A5 levels were not significantly different when SY-005 was administered at the low or the high dose 12-h intervals. There was no significant effect on activated partial thromboplastin time (aPTT) or INR (international normalized ratio of prothrombin time) during 7 days of SY-005 treatment.Conclusion: SY-005 doses of 50 and 100 μg/kg were detectable and subsequently cleared from the plasma in severe COVID-19 patients with normal baseline renal function. There was no significant plasma SY-005 accumulation 6 h after drug administration and coagulation was not altered during 7 days of treatment.Clinical trials Registration: This study was registered with ClinicalTrials.gov (NCT04748757, first posted on 10 February 2021).
Growth and transcriptional response of wheat and rice to the tertiary amine BMVE
Authors: Dharni Jaspinder Singh , Shi Yu , Zhang Chi , Petersen Chris , Walia Harkamal , Staswick Paul 
Published: January 2024

IntroductionSeed vigor is largely a product of sound seed development, maturation processes, genetics, and storage conditions. It is a crucial factor impacting plant growth and crop yield and is negatively affected by unfavorable environmental conditions, which can include drought and heat as well as cold wet conditions. The latter leads to slow germination and increased seedling susceptibility to pathogens. Prior research has shown that a class of plant growth regulators called substituted tertiary amines (STAs) can enhance seed germination, seedling growth, and crop productivity. However, inconsistent benefits have limited STA adoption on a commercial scaleMethodsWe developed a novel seed treatment protocol to evaluate the efficacy of 2-(N-methyl benzyl aminoethyl)-3-methyl butanoate (BMVE), which has shown promise as a crop seed treatment in field trials. Transcriptomic analysis of rice seedlings 24 h after BMVE treatment was done to identify the molecular basis for the improved seedling growth. The impact of BMVE on seed development was also evaluated by spraying rice panicles shortly after flower fertilization and subsequently monitoring the impact on seed traits.ResultsBMVE treatment of seeds 24 h after imbibition consistently improved wheat and rice seedling shoot and root growth in lab conditions. Treated wheat seedlings grown to maturity in a greenhouse also resulted in higher biomass than controls, though only under drought conditions. Treated seedlings had increased levels of transcripts involved in reactive oxygen species scavenging and auxin and gibberellic acid signaling. Conversely, several genes associated with increased reactive oxygen species/ROS load, abiotic stress responses, and germination hindering processes were reduced. BMVE spray increased both fresh and mature seed weights relative to the control for plants exposed to 96 h of heat stress. BMVE treatment during seed development also benefited germination and seedling growth in the next generation, under both ambient and heat stress conditions.DiscussionThe optimized experimental conditions we developed provide convincing evidence that BMVE does indeed have efficacy in plant growth enhancement. The results advance our understanding of how STAs work at the molecular level and provide insights for their practical application to improve crop growth.
Do parent media habits contribute to child global development?
Authors: Fitzpatrick Caroline , Johnson Alexa , Laurent Angélique , Bégin Mathieu , Harvey Elizabeth 
Published: January 2024

Background/objectiveParents of preschoolers’ report using screen media frequently. More frequent screen use by parents may undermine child development by displacing time for foundational parent-child interactions. The objective of the present study is to examine the extent to which parent screen use contributes to child global development 1 year later.MethodsData are from a cohort of 315 preschoolers from Nova Scotia, Canada and their parents during the COVID-19 pandemic. Parents reported the number of hours per day they spent using screens, as well as child screen time and sex, and parent educational attainment. Our outcome is child global development scores, which combine assessments of communication, cognitive, personal-social, and motor skills measured at 4.5 using the Ages and Stages Questionnaire (ASQ) (N = 249, 79% retained).ResultsParents in our sample spent on average 6.35 h per day using screen media outside of work (SD = 3.07) and children spent on average 3.43 h per/day using screens. Multivariate linear regression indicated that each 1-h increase in parents daily screen media use, corresponded to a 1.25 decrease in child global development scores, B = −1.25 p &lt; 0.05, 95% CI between −2.37 and −0.13.ConclusionOur results indicate that parent screen use may represent a key component of children’s media ecology. Given the importance of global development in early childhood for later health and achievement, the present results suggest that interventions should include parent screen use habits in media wellness interventions.
Neurophysiological insights into impaired mentalization in borderline personality disorder an electroencephalography study
Authors: Yun Seokho , Jo So-Hye , Jeon Hye-Jin , Choo Bokyung , Seok Jeong-Ho , Shin Hyunkyung , Kim In-Young , Choi Sun-Woo , Koo Bon-Hoon 
Published: January 2024

IntroductionBorderline personality disorder (BPD) is characterized by interpersonal and emotional instabilities, recurring suicidal tendencies, and feelings of emptiness. Childhood adverse event is reported in 70%–80% of cases involving BPD. Furthermore, the deficiency in mentalization capacity plays a significant role in emotion dysregulation and social interaction problems within individuals with BPD. This study explored the relationship among childhood adverse experiences, mentalization capacity, and neurophysiological activity in patients with BPD.MethodsResting-state electroencephalography was used to identify the neural correlates associated with childhood adversity and mentalization deficits. The participants included 45 patients with BPD and 15 healthy controls.ResultsThe BPD group exhibited reduced alpha activity during eyes-closed rest, indicating heightened arousal even during relaxation. Correlations were found between the power spectral density (PSD) and mentalization capacity in the delta and theta ranges, suggesting an association between PSD and emotional awareness and expression. Gamma activity negatively correlated with psychic equivalence, implying a blurring of the boundaries between internal mental experiences and the external world.ConclusionThese findings offer insights into the pathophysiology of BPD, provide potential diagnostic markers, and suggest personalized treatment approaches based on mentalization traits.
Presence of kratom in opioid overdose deaths: findings from coroner postmortem toxicological report
Authors: Torrico Tyler , Patel Kajal , Nikolov Nicole , Salam Md. Towhid , Padhy Ranjit , Weinstein David 
Published: January 2024

BackgroundKratom (Mitragyna speciosa) use in the United States is becoming increasingly popular and its legal status varies widely from state to state. Multiple reports of adverse events associated with kratom use have ranged from liver injury, seizures, psychiatric disturbance, and rarely death.MethodsThis study investigated coroner autopsy reports from Kern County in California for the year 2020 which included qualitative data on substances from blood toxicological reports. Of the 214 opioid-associated accidental overdoses reported, 4 subjects (1.9%) had mitragynine (kratom) exposure on the autopsy report and were included in the study. We reported available demographic information and comorbid substance findings from the associated autopsy reports.ResultsAll 4 individuals with mitragynine (kratom) toxicology had accidental opioid overdose deaths noted in autopsy reports. Each subject also had toxicology positive for at least one other substance. Fentanyl was found in 3 (75%) of the cases and suspected to be the primary contributor to opioid-related deaths in those cases. However, one fatality was without fentanyl, but instead had tested positive for benzodiazepines, cannabis, and other psychiatric medications.DiscussionThe findings of this brief report provide insight into the role that mitragynine (kratom) may have in modulating risk of opioid-related deaths. The combined use of kratom with opioids such as fentanyl appears most likely to increase the risk of a fatal overdose, but it may also occur with other medications such as benzodiazepines and psychiatric medications. It is a serious concern that in the midst of the opioid overdose epidemic there is a growing presence of kratom use in the U.S. population with a largely unregulated status.
Study on the burden of digestive diseases among Chinese residents in the 21st century
Authors: Gong Shijun , Zhang Yuyu , Wang Yaqiong , Yang Xianhu , Cheng Baolian , Song Ziyi , Liu Xingrong 
Published: January 2024

BackgroundThe global burden of digestive diseases has increased in recent years. The study aims to comprehend the trend of incidence and death rates related to digestive diseases in China from 2000 to 2020.MethodsThe study collected data on digestive diseases and their causes, such as incidence rates, death rates, Years of Life Lost, Years Lived with Disability, Disability-Adjusted Life Years and estimated annual percentage change from the 2019 Global Burden of Disease website and the Chinese Health and Wellness Statistical Yearbook spanning. And we employed the age-period-cohort model to analyze the influence of age, period, and birth cohort on the trend of death rates associated with digestive diseases.ResultsIn contrast to the global burden of digestive disease, China experienced increases in the age-standardized incidence for inflammatory bowel disease, gallbladder and biliary diseases, as well as appendicitis from 2000 to 2019. The corresponding estimated annual percentage change for these diseases were 2.06, 1.74, and 0.99. Females showed a significantly higher incidence of digestive diseases, while males experienced a higher death rate. Moreover, individuals in the age groups under 5 years and over 60 years exhibited higher death rates than those in other age groups.ConclusionThe findings underscore the ongoing importance of digestive diseases as a substantial public health issue in China. Reducing the disease burden of IBD in China necessitates healthcare systems to enhance their infrastructure and personnel readiness, ensuring an equitable, affordable, and accessible distribution of care for IBD patients. To reduce the occurrence and mortality rates of digestive diseases in China, the government should promote the adoption of early screening policies for individuals under the 5 year and those above the 60 year. These policies should be accompanied by customized preventive measures.
ZmGRAS46 Negatively Regulates Flowering Time in Arabidopsis thaliana
Authors: Zhang Honglin , Jiang Zhenzhong , Jiao Peng , Zhao Yang , Gao Bai , Liu Siyan , Guan Shuyan , Ma Yiyong 
Published: January 2024

Flowering is an essential process in plant development, and there are six major flowering pathways: the photoperiodic pathway, gibberellin pathway, vernalization pathway, age pathway, autonomous pathway, and temperature pathway. In this study, we screened the transcriptome sequencing of early flowering mutants from the laboratory for the significantly differentially expressed ZmGRAS46, which belongs to the DELLA subfamily of the GRAS family. DELLA is involved in the gibberellin pathway to regulate plant flowering. However, it is not clear whether ZmGRAS46 is involved in the gibberellin pathway which regulates plant flowering; therefore, in this experiment, we investigated the regulatory role of this gene in Arabidopsis flowering by overexpressing ZmGRAS46. It was found that overexpression of ZmGRAS46 in Arabidopsis promotes the formation of rosette leaves and flower buds and delays flowering time in Arabidopsis, and experiments have shown that ZmGRAS46 represses the expression of FLOWERING LOCUS T (FT), SUPPRESSOR OF CONSTANS1 (SOC1), CONSTANS (CO), and LEAFY (LFY). Our results indicated the possibility that ZmGRAS46 represses flowering through the CO-FT-SOC1-mediated photoperiodic flowering pathway. The delayed flowering phenotype of overexpressing ZmGRAS46 Arabidopsis could be rescued by applying GA3. The experimental results indicate that ZmGRAS46 depends on the GA3 pathway to regulate flowering in Arabidopsis.