bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study reveals markers and candidate genes associated with growth in the rice flower carp, an economic fish species of integrated rice-fish culture in China
Authors: Luo Hui , Pan Xianhui , Huang Yin , Li Zhe , Ye Hua , Zhou Kangqi , Wen Luting , Qin Junqi , He Wenping , Du Xuesong , Wang Dapeng , Lin Yong
Published: February 2023

The rice flower carp (Cyprinus carpio) is an important fish in integrated rice-fishery farming. Here, we performed the first genome-wide association study (GWAS) for seven growth traits (including body mass, total length, body length, body height, body width, caudal-peduncle depth, and eye spacing) in 200 rice flower carp samples using 369,688 high-quality SNPs and 42,225 indels obtained by double-digest genotyping-by-sequencing (ddGBS). The morphometrics of these traits were highly correlated (Pearson’s correlation coefficients = 0.74–0.99, p < 0.001). GWAS detected 15, 5, 4, 26, 7, 16, and 17 loci significant associated (-log10P ≥ 5) with body mass, total length, body length, body width, body height, caudal-peduncle depth, and eye spacing, respectively. Subsequently, within the 50 kb upstream and downstream regions surrounding these significant loci, 38, 19, 18, 20, 52, 27, and 37 candidate genes for the seven growth traits were detected, respectively. Importantly, B6_4352672 and A8_4978825 were significantly associated with more than five growth traits. These results showed loci significantly associated with more than five growth traits will be helpful for future marker-assisted selection (MAS). Interestingly, chromosomes A8 and B25 had many loci significantly associated with growth traits, most of which were shared among multiple growth-related traits. These results indicated that chromosome A8 and B25 may be closely related to growth traits. Our findings not only help understand the genetic architecture of growth traits in fish but facilitate the identification of candidate genes for marker-assisted selection towards breeding faster-growing rice flower carp in the future.
Risk factors associated with positive bacterial culture in salvaged red blood cells during cardiac surgery and postoperative infection incidence: A prospective cohort study
Authors: Zhou Yenong , Chen Tao , Yang Chen , Liu Jincheng , Yang Xiuling , Zhang Bing , Jin Zhenxiao
Published: February 2023

Background

This study was designed to explore factors associated with the incidence of positive bacterial culture of salvaged red blood cells (sRBCs) recovered with a Cell Saver instrument during cardiac surgery and the impact of such positive outcomes on postoperative infection-related morbidity.

Methods

The cohort study enrolled 204 patients scheduled for cardiac surgery with intraoperative blood cell salvage and retransfusion from July 2021 to July 2022. These patients were stratified into two groups based on intraoperative sRBCs bacterial culture results: culture (+) and culture (−) groups. Preoperative and intraoperative variables were compared between these groups aim to detect possible predictors of positive culture in sRBCs. In addition, differences in postoperative infection-related morbidity and other clinical outcomes were compared between these groups.

Results

Of these patients, 49% were sRBCs culture (+), with Staphylococcus epidermidis as the most commonly identified pathogen. Risk factors independently associated with the risk of positive culture in sRBCs included BMI ≥25 kg/m2, a history of smoking, an operative duration ≥277.5 min, the higher number of staff in the operating room and higher surgical case order. Patients in the sRBCs culture (+) group exhibited a longer average ICU stay [3.5 days (2.0–6.0) vs. 2 days (1.0–4.0), P < 0.01], a longer duration of ventilation [20.45 h (12.0–17.8) vs. 13 h (11.0–17.0, P = 0.02)], underwent more allogeneic blood transfusions, exhibited higher transfusion-related costs [2,962 (1,683.0–5,608.8) vs. 2,525 (1,532.3–3,595.0), P = 0.01], and had higher rates of postoperative infections (22 vs. 9.6%, P = 0.02) as compared to patients in the sRBCs culture (−) group. In addition, culture (+) in sRBCs was an independent risk factor for postoperative infection (OR 2.62, 95% CI 1.16–5.90, P = 0.02).

Conclusion

Staphylococcus epidermidis was the most common pathogen detected in sRBCs in the culture (+) group in this study, identifying it as a potential driver of postoperative infection. Positive sRBCs culture may contribute to postoperative infection and its incidence was significantly associated with patient BMI, history of smoking, operative duration, the number of staff in the operating room and surgical case order.
Polynitroxylated PEGylated hemoglobin protects pig brain neocortical gray and white matter after traumatic brain injury and hemorrhagic shock
Authors: Wang Jun , Shi Yanrong , Cao Suyi , Liu Xiuyun , Martin Lee J. , Simoni Jan , Soltys Bohdan J. , Hsia Carleton J. C. , Koehler Raymond C.
Published: February 2023

Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as an anti-inflammatory carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a porcine model of traumatic brain injury (TBI) with and without accompanying hemorrhagic shock (HS). TBI was produced by controlled cortical impact over the frontal lobe of anesthetized juvenile pigs. Hemorrhagic shock was induced starting 5 min after TBI by 30 ml/kg blood withdrawal. At 120 min after TBI, pigs were resuscitated with 60 ml/kg lactated Ringer's (LR) or 10 or 20 ml/kg PNPH. Mean arterial pressure recovered to approximately 100 mmHg in all groups. A significant amount of PNPH was retained in the plasma over the first day of recovery. At 4 days of recovery in the LR-resuscitated group, the volume of frontal lobe subcortical white matter ipsilateral to the injury was 26.2 ± 7.6% smaller than homotypic contralateral volume, whereas this white matter loss was only 8.6 ± 12.0% with 20-ml/kg PNPH resuscitation. Amyloid precursor protein punctate accumulation, a marker of axonopathy, increased in ipsilateral subcortical white matter by 132 ± 71% after LR resuscitation, whereas the changes after 10 ml/kg (36 ± 41%) and 20 ml/kg (26 ± 15%) PNPH resuscitation were not significantly different from controls. The number of cortical neuron long dendrites enriched in microtubules (length >50 microns) decreased in neocortex by 41 ± 24% after LR resuscitation but was not significantly changed after PNPH resuscitation. The perilesion microglia density increased by 45 ± 24% after LR resuscitation but was unchanged after 20 ml/kg PNPH resuscitation (4 ± 18%). Furthermore, the number with an activated morphology was attenuated by 30 ± 10%. In TBI pigs without HS followed 2 h later by infusion of 10 ml/kg LR or PNPH, PNPH remained neuroprotective. These results in a gyrencephalic brain show that resuscitation from TBI + HS with PNPH protects neocortical gray matter, including dendritic microstructure, and white matter axons and myelin. This neuroprotective effect persists with TBI alone, indicating brain-targeting benefits independent of blood pressure restoration.
Willis covered stent treatment for blood blister-like aneurysm: A meta-analysis of efficacy and safety
Authors: Tan Jiahe , Song Rui , Luo Siyue , Fu Wenqiao , Su Jun , He Zhaohui
Published: February 2023

Background

Blood blister-like aneurysm (BBA) is a rare and special type of intracranial aneurysm with extremely high rates of rupture, morbidity, mortality, and recurrence. Willis Covered Stent (WCS) is a new device that is specifically designed for the treatment of intracranial complex aneurysms. However, the efficacy and safety of WCS treatment for BBA remain controversial. Thus, a high level of evidence is required to prove the efficacy and safety of WCS treatment.

Methods

A systematic literature review was performed using a comprehensive literary search in Medline, Embase, and Web of Science databases to identify studies related to WCS treatment for BBA. A meta-analysis was then conducted to incorporate the efficacy and safety outcomes, including intraoperative situation, post-operative situation, and follow-up data.

Results

Eight non-comparative studies containing 104 patients with 106 BBAs met the inclusion criteria. In the intraoperative situation, the technical success rate was 99.5% [95% confidence interval (CI), 0.958, 1.000], the complete occlusion rate was 98.2% (95% CI, 0.925, 1.000), and the side branch occlusion rate was 4.1% (95% CI, 0.001, 0.114). Vasospasm and dissection occurred in 9.2% (95% CI, 0.000, 0.261) and 0.1% (95% CI, 0.000, 0.032) of the patients, respectively. In the post-operative situation, the rebleed and mortality rates were 2.2% (95% CI, 0.000, 0.074) and 1.5% (95% CI, 0.000, 0.062), respectively. In the follow-up data, recurrence and parent artery stenosis occurred in 0.3% (95% CI, 0.000, 0.042) and 9.1% (95% CI, 0.032, 0.168) of the patients, respectively. Ultimately, 95.7% (95% CI, 0.889, 0.997) of the patients had a good outcome.

Conclusions

Willis Covered Stent could be effectively and safely applied for BBA treatment. The results provide a reference for clinical trials in the future. Well-designed prospective cohort studies must be conducted for verification.
Peripheral eosinophil trends and clinical outcomes after non-traumatic subarachnoid hemorrhage
Authors: Gonzalez Gomez Hugo , Savarraj Jude P. J. , Paz Atzhiry S. , Ren Xuefang , Chen Hua , McCullough Louise D. , Choi Huimahn A. , Gusdon Aaron M.
Published: February 2023

Background/objective

Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH.

Methods

This retrospective observational study included patients with SAH admitted from January 2009 to July 2016. Variables included demographics, modified Fisher scale (mFS), Hunt–Hess Scale (HHS), global cerebral edema (GCE), and the presence of any infection. Peripheral eosinophil counts were examined as part of routine clinical care on admission and daily for 10 days after aneurysmal rupture. Outcome measures included dichotomized discharge mortality, modified Ranked Scale (mRS) score, delayed cerebral ischemia (DCI), vasospasm, and need for ventriculoperitoneal shunt (VPS). Statistical tests included the chi-square test, Student's t-test, and multivariable logistic regression (MLR) model.

Results

A total of 451 patients were included. The median age was 54 (IQR 45, 63) years, and 295 (65.4%) were female patients. On admission, 95 patients (21.1%) had a high HHS (>4), and 54 (12.0%) had GCE. A total of 110 (24.4%) patients had angiographic vasospasm, 88 (19.5%) developed DCI, 126 (27.9%) had an infection during hospitalization, and 56 (12.4%) required VPS. Eosinophil counts increased and peaked on days 8–10. Higher eosinophil counts on days 3–5 and day 8 were seen in patients with GCE (p < 0.05). Higher eosinophil counts on days 7–9 (p < 0.05) occurred in patients with poor discharge functional outcomes. In multivariable logistic regression models, higher day 8 eosinophil count was independently associated with worse discharge mRS (OR 6.72 [95% CI 1.27, 40.4], p = 0.03).

Conclusion

This study demonstrated that a delayed increase in eosinophils after SAH occurs and may contribute to functional outcomes. The mechanism of this effect and the relationship with SAH pathophysiology merit further investigation.
Low-dose vs. standard-dose alteplase for Chinese patients with acute ischemic stroke: A propensity score analysis
Authors: Xu Jiawen , Chen Xi , Xie Yanan , Wang Yi , Chen Shidong , Dong Qiang , Dong Yi , Fang Kun
Published: February 2023

Background and purpose

Previous studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry.

Methods

We analyzed data from the Shanghai Stroke Service System. Patients receiving alteplase intravenous thrombolysis within 4.5 hours were included. These patients were divided into the low-dose alteplase group (0.55–0.65 mg/kg) and the standard-dose alteplase group (0.85–0.95 mg/kg). Baseline imbalances were adjusted by using the propensity score matching. The primary outcome was mortality or disability, which was defined as the modified Rankin scale (mRS) score ranging from 2 to 6 at discharge. The secondary outcomes were in-hospital mortality, symptomatic intracranial hemorrhage (sICH) and functional independence (mRS score 0–2).

Results

From January 2019 to December 2020, a total of 1,334 patients were enrolled and 368 (27.6%) were treated with low-dose alteplase. The median age of the patients was 71 years, and 38.8% were female. Our study showed that the low-dose group had significantly higher rates of death or disability (adjusted odds ratio (aOR) = 1.49, 95% confidence interval (CI) [1.12, 1.98]) and less functional independence (aOR = 0.71, 95%CI [0.52, 0.97]) than the standard-dose group. There was no significant difference in sICH or in-hospital mortality between the standard-dose and low-dose alteplase groups.

Conclusions

Low-dose alteplase was related to a poor functional outcome without lowering the risk of sICH, compared with standard-dose alteplase for AIS patients in China.
Associations between the pupil light reflex and the broader autism phenotype in children and adults
Authors: Soker-Elimaliah Sapir , Lehrfield Aviva , Scarano Samuel R. , Wagner Jennifer B.
Published: February 2023

The pupil light reflex (PLR), a marker of neuronal response to light, is a well-studied index of autonomic functioning. Studies have found that autistic children and adults have slower and weaker PLR responses compared to non-autistic peers, suggesting lower autonomic control. Altered autonomic control has also been associated with increased sensory difficulties in autistic children. With autistic traits varying in the general population, recent studies have begun to examine similar questions in non-autistic individuals. The current study looked at the PLR in relation to individual differences in autistic traits in non-autistic children and adults, asking how differences in the PLR could lead to variation in autistic traits, and how this might change across development. Children and adults completed a PLR task as a measure of sensitivity to light and autonomic response. Results showed that, in adults, increased levels of restricted and repetitive behaviors (RRB) were associated with a weaker and slower PLR. However, in children, PLR responses were not associated with autistic traits. Differences in PLR were also found across age groups, with adults showing smaller baseline pupil diameter and stronger PLR constriction as compared with children. The current study expanded on past work to examine the PLR and autistic traits in non-autistic children and adults, and the relevance of these findings to sensory processing difficulties is discussed. Future studies should continue to examine the neural pathways that might underlie the links between sensory processing and challenging behaviors.
Solifenacin versus posterior tibial nerve stimulation for overactive bladder in patients with multiple sclerosis
Authors: Majdinasab Nastaran , Orakifar Neda , Kouti Leila , Shamsaei Gholamreza , Seyedtabib Maryam , Jafari Mohammad
Published: February 2023

Introduction

Overactive bladder (OAB) is one of the most common complications in patients with multiple sclerosis (MS). Choosing the effective treatment is very important in improving their quality of life (QOL). Therefore, the aim of this study was to compare solifenacin (SS) and posterior tibial nerve stimulation (PTNS) treatment effects in the MS Patients with OAB.

Materials and methods

In total, 70 MS patients suffering from OAB enrolled in this clinical trial study. Patients with a score of at least 3 according to the OAB questionnaire were randomly divided into two groups (35 patients in each group). In one group, patients received SS (5 mg daily for 4 weeks and 10 mg/day for another 8 weeks) and in a second group, patients were treated by PTNS (12 weekly session, 30 min).

Results

The mean (SD) age of patients participating in this study was 39.82 (9.088) and 42.41 (9.175) years for the SS group and the PTNS group, respectively. Patients in both groups showed statistically significant improvements in urinary incontinence, micturition, and daytime frequency (p < 0.001). Patients in the SS group had a better response for urinary incontinence after 12 weeks compared to the PTNS group. Also, patients in the SS group reported higher satisfaction and less daytime frequency compared to the PTNS group.

Conclusion

SS and PTNS were effective for improving the OAB symptoms in patients with MS. However, patients demonstrated a better experience with SS in terms of daytime frequency, urinary incontinence, and treatment satisfaction rate.
Associations between dietary and blood inflammatory indices and their effects on cognitive function in elderly Americans
Authors: Li Wanyue , Li Shuna , Shang Yaru , Zhuang Weisheng , Yan Guoqiang , Chen Zhuoming , Lyu Jun
Published: February 2023

Objective

To determine the correlations between dietary and blood inflammation indices in elderly Americans and their effects on cognitive function.

Methods

This research extracted data from the 2011–2014 National Health and Nutrition Examination Survey for 2,479 patients who were ≥60 years old. Cognitive function was assessed as a composite cognitive function score (Z-score) calculated from the results of the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning and Delayed Recall tests, the Animal Fluency test, and the Digit Symbol Substitution Test. We used a dietary inflammatory index (DII) calculated from 28 food components to represent the dietary inflammation profile. Blood inflammation indicators included the white blood cell count (WBC), neutrophil count (NE), lymphocyte count (Lym), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), neutrophil–albumin ratio (NAR), systemic immune-inflammation index [SII, calculated as (peripheral platelet count) × NE/Lym], and systemic inflammatory response index [SIRI, calculated as (monocyte count) × NE/Lym]. WBC, NE, Lym, NLR, PLR, NAR, SII, SIRI, and DII were initially treated as continuous variables. For logistic regression, WBC, NE, Lym, NLR, PLR, NAR, SII, and SIRI were divided into quartile groups, and DII was divided into tertile groups.

Results

After adjusting for covariates, WBC, NE, NLR, NAR, SII, SIRI, and DII scores were markedly higher in the cognitively impaired group than in the normal group (p < 0.05). DII was negatively correlated with the Z-score when combined with WBC, NE, and NAR (p < 0.05). After adjusting for all covariates, DII was positively correlated with SII in people with cognitive impairment (p < 0.05). Higher DII with NLR, NAR, SII, and SIRI all increased the risk of cognitive impairment (p < 0.05).

Conclusion

DII was positively correlated with blood inflammation indicators, and higher DII and blood inflammation indicators increased the risk of developing cognitive impairment.
m6A methylation: Critical roles in aging and neurological diseases
Authors: Fan Yishu , Lv Xinyi , Chen Zhuohui , Peng Yanyi , Zhang Mengqi
Published: February 2023

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.
Transforming experiences: Neurobiology of memory updating/editing
Authors: Osorio-Gómez Daniel , Miranda Maria Isabel , Guzmán-Ramos Kioko , Bermúdez-Rattoni Federico
Published: February 2023

Long-term memory is achieved through a consolidation process where structural and molecular changes integrate information into a stable memory. However, environmental conditions constantly change, and organisms must adapt their behavior by updating their memories, providing dynamic flexibility for adaptive responses. Consequently, novel stimulation/experiences can be integrated during memory retrieval; where consolidated memories are updated by a dynamic process after the appearance of a prediction error or by the exposure to new information, generating edited memories. This review will discuss the neurobiological systems involved in memory updating including recognition memory and emotional memories. In this regard, we will review the salient and emotional experiences that promote the gradual shifting from displeasure to pleasure (or vice versa), leading to hedonic or aversive responses, throughout memory updating. Finally, we will discuss evidence regarding memory updating and its potential clinical implication in drug addiction, phobias, and post-traumatic stress disorder.
Intake of omega-3 polyunsaturated fatty acids and fish associated with prevalence of low lean mass and muscle mass among older women: Analysis of Korea National Health and Nutrition Examination Survey, 2008-2011
Authors: Kim Yeji , Park Yongsoon
Published: February 2023

The effects of dietary n-3 PUFA and fish on the risk of sarcopenia and muscle mass remain unclear. The present study investigated the hypothesis that intake of n-3 PUFA and fish is negatively associated with the prevalence of low lean mass (LLM) and positively correlated with muscle mass in older adults. Data from the Korea National Health and Nutrition Examination Survey, 2008-2011, 1,620 men and 2,192 women aged over 65 years were analyzed. LLM was defined as appendicular skeletal muscle mass divided by body mass index < 0.789 kg for men and <0.512 kg for women. Women and men with LLM consumed less eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA) and fish. In women, but not men, the prevalence of LLM was associated with the intake of EPA and DHA (odds ratio, 0.65; 95% confidence interval, 0.48-0.90; p = 0.002) and fish (odds ratio, 0.59; 95% confidence interval, 0.42-0.82; p < 0.001). Muscle mass was also positively associated with the intake of EPA, DHA (p = 0.026), and fish (p = 0.005) in women, but not men. α-Linolenic acid intake was not associated with the prevalence of LLM and was not correlated with muscle mass. The findings suggest that consumption of EPA, DHA, and fish are negatively associated with the prevalence of LLM, and positively correlated with muscle mass in Korean older women, but not in older men.
Prophylactic inguinal lymphadenectomy for high-risk cN0 penile cancer: The optimal surgical timing
Authors: Ma Shanjin , Zhao Jian , Liu Zhiwei , Wu Tao , Wang Sheng , Wu Chengwen , Pan Lei , Jiang Xiaoye , Guan Zhihao , Wang Yanjun , Jiao Dian , Yan Fengqi , Zhang Keying , Tang Qisheng , Ma Jianjun
Published: February 2023

Background

Few reports have investigated the oncologically safe timing of prophylactic inguinal lymphadenectomy for penile cancer patients with clinically normal inguinal lymph nodes (cN0), particularly those who received delayed surgical treatment.

Methods

The study included pT1aG2, pT1b-3G1-3 cN0M0 patients with penile cancer who received prophylactic bilateral inguinal lymph nodes dissection (ILND) at the Department of Urology of Tangdu Hospital between October 2002 and August 2019. Patients who received simultaneous resection of primary tumor and inguinal lymph nodes were assigned to the immediate group, while the rest were assigned to the delayed group. The optimal timing of lymphadenectomy was determined based on the time-dependent ROC curves. The disease-specific survival (DSS) was estimated based on the Kaplan–Meier curve. Cox regression analysis was used to evaluate the associations between DSS and the timing of lymphadenectomy and tumor characteristics. The analyses were repeated after stabilized inverse probability of treatment weighting adjustment.

Results

A total of 87 patients were enrolled in the study, 35 of them in the immediate group and 52 in the delayed group. The median (range) interval time between primary tumor resection and ILND of the delayed group was 85 (29-225) days. Multivariable Cox analysis demonstrated that immediate lymphadenectomy was associated with a significant survival benefit (HR, 0.11; 95% CI, 0.02–0.57; p = 0.009). An index of 3.5 months was determined as the optimal cut-point for dichotomization in the delayed group. In high-risk patients who received delayed surgical treatment, prophylactic inguinal lymphadenectomy within 3.5 months was associated with a significantly better DSS compared to dissection after 3.5months (77.8% and 0%, respectively; log-rank p<0.001).

Conclusions

Immediate and prophylactic inguinal lymphadenectomy in high-risk cN0 patients (pT1bG3 and all higher stage tumours) with penile cancer improves survival. For those patients at high risk who received delayed surgical treatment for any reason, within 3.5 months after resection of the primary tumor seems to be an oncologically safe window for prophylactic inguinal lymphadenectomy.
Prognostic value of lipid profile in adult hemophagocytic lymphohistiocytosis
Authors: Cheng Wanying , Wang Lingling , Gao Xin , Duan Limin , Shu Yongqian , Qiu Hongxia
Published: February 2023

Background

Adult secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare clinical syndrome with a high mortality rate. Currently, there are no feasible prognostic factors to clinically predict untreated sHLH patients’ prognosis. Our objective was to characterize the lipid profile of adult sHLH patients and to determine the relationship with overall survival.

Methods

We retrospectively analyzed 247 patients with newly diagnosed sHLH from January 2017 to January 2022 according to the HLH-2004 criteria. Multivariate Cox regression analyses and restricted cubic splines were conducted to evaluate the prognostic value of the lipid profile.

Results

The median age of all patients was 52 years, and the commonest cause of sHLH in our cohort was malignancy. During a median follow-up of 88 (interquartile ranges, 22–490) days, 154 deaths occurred. The univariate analysis confirmed total cholesterol (TC) ≤ 3 mmol/L, triglycerides (TG) > 3.08 mmol/L, high-density lipoprotein cholesterol (HDL-c) ≤ 0.52 mmol/L, and low-density lipoprotein cholesterol (LDL-c) ≤ 2.17 mmol/L were associated with an inferior survival. In a multivariate model, HDL-c, hemoglobin, platelet, fibrinogen, and soluble interleukin-2 receptor were considered as independent factors. Additionally, the restricted cubic spline analyses indicated an inverse linear association between HDL-c and the risk of mortality in sHLH.

Conclusion

Lipid profiles, which were low-cost and readily available promising biomarkers, were strongly associated with the overall survival in adult sHLH patients.
Maximal safe resection of diffuse lower grade gliomas primarily within central lobe using cortical/subcortical direct electrical stimulation under awake craniotomy
Authors: Yao Shujing , Yang Ruixin , Du Chenggang , Jiang Che , Wang Yang , Peng Chongqi , Bai Hongmin
Published: February 2023

Background

Diffuse lower-grade glioma (DLGG) in the central lobe is a challenge for safe resection procedures. To improve the extent of resection and reduce the risk of postoperative neurological deficits, we performed an awake craniotomy with cortical-subcortical direct electrical stimulation (DES) mapping for patients with DLGG located primarily within the central lobe. We investigated the outcomes of cortical-subcortical brain mapping using DES in an awake craniotomy for central lobe DLGG resection.

Methods

We performed a retrospective analysis of clinical data of a cohort of consecutively treated patients from February 2017 to August 2021 with diffuse lower-grade gliomas located primarily within the central lobe. All patients underwent awake craniotomy with DES for cortical and subcortical mapping of eloquent brain areas, neuronavigation, and/or ultrasound to identify tumor location. Tumors were removed according to functional boundaries. Maximum safe tumor resection was the surgical objective for all patients.

Results

Thirteen patients underwent 15 awake craniotomies with intraoperative mapping of eloquent cortices and subcortical fibers using DES. Maximum safe tumor resection was achieved according to functional boundaries in all patients. The pre-operative tumor volumes ranged from 4.3 cm3 to 137.3 cm3 (median 19.2 cm3). The mean extent of tumor resection was 94.6%, with eight cases (53.3%) achieving total resection, four (26.7%) subtotal and three (20.0%) partial. The mean tumor residue was 1.2 cm3. All patients experienced early postoperative neurological deficits or worsening conditions. Three patients (20.0%) experienced late postoperative neurological deficits at the 3-month follow-up, including one moderate and two mild neurological deficits. None of the patients experienced late onset severe neurological impairments post-operatively. Ten patients with 12 tumor resections (80.0%) had resumed activities of daily living at the 3-month follow-up. Among 14 patients with pre-operative epilepsy, 12 (85.7%) were seizure-free after treatment with antiepileptic drugs 7 days after surgery up to the last follow-up.

Conclusions

DLGG located primarily in the central lobe deemed inoperable can be safely resected using awake craniotomy with intraoperative DES without severe permanent neurological sequelae. Patients experienced an improved quality of life in terms of seizure control.
Genome-wide identification of A-to-I RNA editing events provides the functional implications in PDAC
Authors: Mei Yue , Liang Dong , Ai Bin , Wang Tengjiao , Guo Shiwei , Jin Gang , Yu Dong
Published: February 2023

Introduction

RNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.

Method

We characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.

Result

A large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.

Conclusion

RNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.
Elicitation of domain knowledge for a machine learning model for paediatric critical illness in South Africa
Authors: Pienaar Michael A. , Sempa Joseph B. , Luwes Nicolaas , George Elizabeth C. , Brown Stephen C.
Published: February 2023

Objectives

Delays in identification, resuscitation and referral have been identified as a preventable cause of avoidable severity of illness and mortality in South African children. To address this problem, a machine learning model to predict a compound outcome of death prior to discharge from hospital and/or admission to the PICU was developed. A key aspect of developing machine learning models is the integration of human knowledge in their development. The objective of this study is to describe how this domain knowledge was elicited, including the use of a documented literature search and Delphi procedure.

Design

A prospective mixed methodology development study was conducted that included qualitative aspects in the elicitation of domain knowledge, together with descriptive and analytical quantitative and machine learning methodologies.

Setting

A single centre tertiary hospital providing acute paediatric services.

Participants

Three paediatric intensivists, six specialist paediatricians and three specialist anaesthesiologists.

Interventions

None.

Measurements and main results

The literature search identified 154 full-text articles reporting risk factors for mortality in hospitalised children. These factors were most commonly features of specific organ dysfunction. 89 of these publications studied children in lower- and middle-income countries. The Delphi procedure included 12 expert participants and was conducted over 3 rounds. Respondents identified a need to achieve a compromise between model performance, comprehensiveness and veracity and practicality of use. Participants achieved consensus on a range of clinical features associated with severe illness in children. No special investigations were considered for inclusion in the model except point-of-care capillary blood glucose testing. The results were integrated by the researcher and a final list of features was compiled.

Conclusion

The elicitation of domain knowledge is important in effective machine learning applications. The documentation of this process enhances rigour in such models and should be reported in publications. A documented literature search, Delphi procedure and the integration of the domain knowledge of the researchers contributed to problem specification and selection of features prior to feature engineering, pre-processing and model development.
Trend analysis of mortality rates and causes of death in children under 5 years of age in Xuzhou, China from 2016 to 2020
Authors: Xu Zhiyuan , Liu Haonan , Zhou Shuaishuai , Chen Tiancheng , Meng Chao , Li Shengli , Yan Xianliang , Liu Xiao
Published: February 2023

Objectives

To analyze the trends in mortality and causes of death among children under 5 years of age in Xuzhou, China between 2016 and 2020, in order to protect children's health and provide a basis for formulating child survival, development, and protection strategies.

Methods

A population-based epidemiological study was conducted. Data were obtained from the Xuzhou Center for Disease Control Prevention. We input the data into the excel database and analyzed with SPSS20.0.

Results

There were 1,949 children under 5 years of age died in Xuzhou, The number of deaths from 2016 to 2020 were 573 (29.40%), 577 (29.60%), 371 (19.04%), 334 (17.14%), and 94 (4.82%) respectively, mortality in children showed a downward trend. The number of deaths was relatively high in January (195 cases, 10.01%), February (190 cases, 9.75%), and May (180 cases, 9.24%), while was relatively small in July (147 cases, 7.54%), August (139 cases, 7.13%), and September (118 cases, 6.05%). The leading causes of death (COD) in children under 5 years of age were neonatal suffocation and hypoxia (323 cases, 16.57%). Pizhou (528 cases, 27.09%) showed the highest number of deaths in children under 5 years of age in China, and the Kaifa (25 cases, 1.28%) zone showed the lowest death toll.

Conclusions

Our research suggested that the current strategies for reducing child mortality should prioritize the actions on neonatal deaths and conduct targeted interventions for the main cause.
Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review
Authors: Balalian Arin A. , Graeve Richard , Richter Matthias , Fink Astrid , Kielstein Heike , Martins Silvia S. , Philbin Morgan M. , Factor-Litvak Pam
Published: February 2023

Aim

This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies.

Methods

We searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using “Covidence” systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment.

Results

Data were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis.

Conclusion

We explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.
3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma
Authors: Lian Zheng , Sang Chenglin , Li Nianhu , Zhai Honglin , Bai Wenzhe
Published: February 2023

Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds.

Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models.

Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4).

Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q2 (0.63) and R2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability.

Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma.
A molecular perspective on the invasibility of the southern ocean benthos: The impact of hypoxia and temperature on gene expression in South American and Antarctic Aequiyoldia bivalves
Authors: Martínez Mariano , González-Aravena Marcelo , Held Christoph , Abele Doris
Published: February 2023

When an organism makes a long-distance transition to a new habitat, the associated environmental change is often marked and requires physiological plasticity of larvae, juveniles, or other migrant stages. Exposing shallow-water marine bivalves (Aequiyoldia cf. eightsii) from southern South America (SSA) and the West Antarctic Peninsula (WAP) to changes in temperature and oxygen availability, we investigated changes in gene expression in a simulated colonization experiment of the shores of a new continent after crossing of the Drake Passage, and in a warming scenario in the WAP. Bivalves from SSA were cooled from 7°C (in situ) to 4°C and 2°C (future warmed WAP conditions), WAP bivalves were warmed from 1.5°C (current summer in situ) to 4°C (warmed WAP), gene expression patterns in response to thermal stress by itself and in combination with hypoxia were measured after 10 days. Our results confirm that molecular plasticity may play a vital role for local adaptation. Hypoxia had a greater effect on the transcriptome than temperature alone. The effect was further amplified when hypoxia and temperature acted as combined stressors. The WAP bivalves showed a remarkable ability to cope with short-term exposure to hypoxia by switching to a metabolic rate depression strategy and activating the alternative oxidation pathway, whilst the SSA population showed no comparable response. In SSA, the high prevalence of apoptosis-related differentially expressed genes especially under combined higher temperatures and hypoxia indicated that the SSA Aequiyoldia are operating near their physiological limits already. While the effect of temperature per se may not represent the single most effective barrier to Antarctic colonization by South American bivalves, the current distribution patterns as well as their resilience to future conditions can be better understood by looking at the synergistic effects of temperature in conjunction with short-term exposure to hypoxia.
From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network
Authors: Shiiya Tomohiro , Hirashima Masanori
Published: February 2023

During development, lymphatic endothelial cell (LEC) progenitors differentiate from venous endothelial cells only in limited regions of the body. Thus, LEC migration and subsequent tube formation are essential processes for the development of tubular lymphatic vascular network throughout the body. In this review, we discuss chemotactic factors, LEC-extracellular matrix interactions and planar cell polarity regulating LEC migration and formation of tubular lymphatic vessels. Insights into molecular mechanisms underlying these processes will help in understanding not only physiological lymphatic vascular development but lymphangiogenesis associated with pathological conditions such as tumors and inflammation.
Unlocking the potentials of nitrate transporters at improving plant nitrogen use efficiency
Authors: Aluko Oluwaseun Olayemi , Kant Surya , Adedire Oluwafemi Michael , Li Chuanzong , Yuan Guang , Liu Haobao , Wang Qian
Published: February 2023

Nitrate (NO3-) transporters have been identified as the primary targets involved in plant nitrogen (N) uptake, transport, assimilation, and remobilization, all of which are key determinants of nitrogen use efficiency (NUE). However, less attention has been directed toward the influence of plant nutrients and environmental cues on the expression and activities of NO3- transporters. To better understand how these transporters function in improving plant NUE, this review critically examined the roles of NO3- transporters in N uptake, transport, and distribution processes. It also described their influence on crop productivity and NUE, especially when co-expressed with other transcription factors, and discussed these transporters’ functional roles in helping plants cope with adverse environmental conditions. We equally established the possible impacts of NO3- transporters on the uptake and utilization efficiency of other plant nutrients while suggesting possible strategic approaches to improving NUE in plants. Understanding the specificity of these determinants is crucial to achieving better N utilization efficiency in crops within a given environment.
Mini-review: Lipid flippases as putative targets for biotechnological crop improvement
Authors: López-Marqués Rosa Laura
Published: February 2023

An increasing world population and drastic changes in weather conditions are challenging agricultural production. To face these challenges and ensure sustainable food production in the future, crop plants need to be improved to withstand several different biotic and abiotic stresses. Commonly, breeders select varieties that can tolerate a specific type of stress and then cross these varieties to stack beneficial traits. This strategy is time-consuming and strictly dependent on the stacked traits been genetically unlinked. Here, we revise the role of plant lipid flippases of the P4 ATPase family in stress-related responses with a special focus on the pleiotropic nature of their functions and discuss their suitability as biotechnological targets for crop improvement.