bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of internal fixation in the treatment of femoral head necrosis with ipsilateral hip fracture
Authors: Zhang Xinguo , Liu Sikai
Published: August 2022

Whether internal fixation or hip arthroplasty is the most appropriate initial treatment for patients with ipsilateral hip fracture and osteonecrosis of the femoral head remains unknown. In this study, the prognoses of patients who underwent internal fixation or hip arthroplasty were analyzed and compared to explore the role of internal fixation in treating such patients.

We retrospectively reviewed 69 patients diagnosed with osteonecrosis of the femoral head and ipsilateral hip fracture from 1999 to 2018. They were divided into the hip arthroplasty or internal fixation group. The visual analog scale and Harris score were used. The incidence of complications and the conversion to arthroplasty were also investigated to further explore the role of internal fixation.

Male patients (male/female: 25/31 vs 20/38, P = .015), younger patients (average age: 46.80 ± 13.14 vs 61.07 ± 15.61, P < .001), and patients with femoral neck fractures (fracture type, femoral neck/trochanter: 21/31 vs 12/38, P = .003) were more likely to receive 1-stage hip arthroplasty. Of 38 patients undergoing internal fixation, fracture nonunion was identified in 9, and progression of osteonecrosis was identified in 16. Meanwhile, conversion to secondary hip arthroplasty occurred in 13 patients. Four independent risk factors for conversion to secondary hip arthroplasty were identified: age of ≤60 years (odds ratio [OR] = 9.786, 95% confidence interval [CI] = 2.735–35.015), male sex (OR = 6.790, 95% CI = 1.718–26.831), collapse of the femoral head before injury (OR = 7.170, 95% CI = 2.004–25.651), and femoral neck fracture (OR = 8.072, 95% CI = 2.153–30.261). A new scoring system was constructed for predicting conversion to hip arthroplasty in patients undergoing internal fixation treatment. A cutoff of ≤2 points indicated low risk for conversion, 3 to 4 points indicated moderate risk, and ≥5 points indicated high risk.

Patients who underwent internal fixation had worse prognoses than those who underwent 1-stage hip arthroplasty. However, in this study, hip arthroplasty conversion did not occur in most patients who received internal fixation. Using the new scoring system to identify patients who may require conversion to replacement may help make appropriate patient management and clinical decisions.
Correlation between endoscopic resection outcomes and endosonographic findings in gastric tumors with muscularis propria origin
Authors: Cho Jinwoong , Han Jihyun , Choi Mirim , Song Jaesun , Yang Mina , Lee Youngjae
Published: August 2022

Endoscopic resection is an effective treatment for subepithelial tumors arising from the muscularis propria layer of the stomach. However, the invasion pattern revealed by the pathological examination of tumor specimens is often not consistent with the findings of preprocedural endoscopic ultrasounds (EUS).

We compared the real growing patterns of tumors, as evaluated on histopathological examination, with their EUS images, and analyzed the outcomes of endoscopic resections in relation to the EUS findings.

From January 2006 to June 2015, 32 patients underwent endoscopic resection for gastric tumors originating from the muscularis propria at our hospital.

We divided the patients into 3 groups according to the location of the tumor as diagnosed using pre procedural EUS: submucosa (group I, n = 5), muscularis propria (group II, n = 14), and tumors extending into the outer cavity (group III, n = 13).

Histopathological examination revealed 15 patients with gastrointestinal stromal tumors (GISTs), 14 with leiomyomas, and 3 with schwannomas. Accuracy of EUS in evaluating tumor invasion was 56%. Some tumors in groups I and II was removed by endoscopic submucosal dissection only. Muscular dissection was needed in 10 patients (71%) in group II and 9 patients (69%) in group III. Four patients (31%) in group III were found to have subserosal tumors. The complete resection rate was 88% (23 patients) among patients who underwent endoscopic submucosal dissection and endoscopic muscular dissection, and 67% (4 patients) among patients who underwent endoscopic subserosal dissection (ESSD). The tumor was completely removed in 12 patients (86%) in group II and 10 patients (77%) in group III.

EUS accurately predicts the layer of the subepithelial tumor in the stomach; however, the pattern of invasion of surrounding structures is difficult to evaluate using EUS.
Effect of low-dose lidocaine on MEPs in patients undergoing intracranial tumor resection with propofol anesthesia: A randomized controlled trial
Authors: Liu Meijuan , Wang Ning , Wang Dong , Liu Juan , Zhou Xuelong , Jin Wenjie
Published: August 2022

Objective:

To investigate the effect of low-dose lidocaine on motor evoked potentials (MEPs) in patients undergoing intracranial tumor resection with propofol anesthesia.

Methods:

Forty patients who underwent intracranial tumor resection and required MEP monitoring were selected. They were randomly divided into the lidocaine group (group L, n = 20) and the control group (group C, n = 20) by computer-generated randomization. All patients were given propofol anesthesia under the guidance of the bispectral index. In group L, 1 mg/kg of lidocaine was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at a speed of 1 mg/kg/h until the operation started. Group C was given an equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and bispectral index were recorded before anesthesia induction (T0), 2 minutes after tracheal intubation (T1), and 35 minutes (T2), and 50 minutes (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol after anesthesia induction, and adverse events before T3 were recorded.

Results:

Compared with those in group C, HR and MAP were significantly decreased at T1 in group L. No significant differences were observed in HR and MAP at T0, T2, and T3 between group L and group C. The total dosage of propofol and the incidence of adverse events were significantly lower in group L than in group C before T3. There were no significant differences in the amplitude and latency of MEP between the 2 groups at each time point.

Conclusions:

Low-dose lidocaine has no obvious effect on MEP in patients undergoing intracranial tumor resection. However, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.
Clinical application of bone turnover markers in treating osteoporotic vertebral compression fractures and their role in predicting fracture progression
Authors: Han Moon-Soo , Lee Gwang-Jun , Lee Seul-Kee , Lee Jung-Kil , Moon Bong Ju
Published: August 2022

This study aimed to investigate whether changes in the bone turnover markers (BTMs) during teriparatide therapy for osteoporotic vertebral compression fractures could reflect therapeutic effects by analyzing the relationship between clinical and radiological features and BTMs.

A total of 33 patients with 51 osteoporotic vertebral compression fracture segments were included. Plain radiographs and BTM levels were evaluated at the pretreatment and at 3 months after teriparatide treatment. Based on serial vertebral compression ratio analysis, the progression of fracture was defined as a vertebral compression ratio decrease of ≥10%, relative to the pretreatment values.

All segments were divided into 2 groups: the “maintain” group with 32 (62.7%) segments and the “progression” group with 19 (37.3%) segments. After the teriparatide treatment, serum osteocalcin and serum C-terminal telopeptide of type I collagen levels (P = .028 and .008, respectively), and change amounts of them were significantly larger, increasing (P = .001) in the progression group. The vitamin D (25OH-D) levels were significantly lower (P = .038) in the progression group; however, the relative changes in the 25OH-D levels between the 2 groups, before and after the treatment, were not significantly different (P = .077). The parathyroid hormone (PTH) levels were reduced by the teriparatide treatment in both groups, while the decrease in PTH concentration after the treatment was significantly more pronounced in the progression group (P = .006). Significant increase in the osteocalcin and serum C-terminal telopeptide of type I collagen levels and a simultaneous decrease in the PTH levels during the teriparatide treatment suggest that clinicians should assume the progression of fracture.
Understanding diagnostic pathways in systemic sclerosis and systemic sclerosis-associated interstitial lung disease: A retrospective cohort study
Authors: Assassi Shervin , Shao Nan , Yin Ziwei , Volkmann Elizabeth R. , Zoz Donald F. , Leonard Thomas B.
Published: August 2022

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optum’s Clinformatics® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients with an SSc index date between October 1, 2017, and June 30, 2019, based on ICD-10-CM codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥2 years of continuous enrollment prior to SSc index date. ILD was defined as ≥2 medical claims associated with ILD on different dates. The ICD-9-CM and ICD-10-CM cohorts comprised 1779 and 1032 patients, respectively. In these cohorts, respectively, 7.6% and 9.3% of patients had their second medical claim associated with ILD prior to their SSc index date, and 4.3% and 5.6% of patients had their second medical claim associated with ILD >1 year prior to the SSc index date. In this analysis, 4% to 6% of patients with SSc had claims for ILD >1 year prior to a claim for SSc. These data show that SSc can affect the lung early and demonstrate the importance of screening patients with SSc for ILD and patients with ILD for SSc.
Preventing effect of astragalus polysaccharide on cardiotoxicity induced by chemotherapy of epirubicin: A pilot study
Authors: Li Xiaofang , Guo Xin , Li Jun , Yuan Li , Wang Haixiong
Published: August 2022

To assess the clinical effect of astragalus polysaccharide in preventing cardiotoxicity induced by chemotherapy of epirubicin. Two hundred forty-eight patients with breast cancer or malignant lymphoma were randomly divided into the experimental group (EG) (n = 124) and the control group (CG) (n = 124). The EG received chemotherapy regimen containing anthracycline epirubicin and astragalus injection, while CG received only chemotherapy regimen containing anthracycline epirubicin. We detected myocardial function (cardiac troponin I [cTnI], creatine kinase isoenzyme [CK-MB], left ventricular ejection fraction [LVEF], and the ratio of mitral annular diastolic peak velocity to atrial systolic velocity [E/A]) and incidences of cardiotoxicity to assess cardiac function, they were compared at before the first treatment course (T1), end of the second course (T2) and 6-month follow-up. We also detected proinflammatory cytokines (IL-6 and TNF-α), reactive oxygen species and antioxidant enzymes, glutathione peroxidase (GPx), and superoxide dismutase (SOD) aimed to discover potential mechanism. There were no statistical significances in differences of LVEF and E/A between 2 groups (P > .05) at T1 and T2, while levels of LVEF and E/A of EG were significant higher than those of the CG at 6 month follow-up, with statistically significant differences (P < .05). At T1, there were no statistical significances in differences of cTnI and CK-MB between 2 groups (P > .05); at T2 and 6 months follow-up, the cTnI, and CK-MB levels of EG was significantly lower than those of the CG, with statistically significant differences (P < .05). The incidence of cardiotoxicity of EG was 15% (17/113), which was significant lower than that of the CG (60%, 66/110), with statistically significant difference (P < .05). Moreover, the level of TNF-α, GPx, and SOD did not show significant difference (P > .05). The data in this pilot study suggested that astragalus polysaccharide may be an effective therapy for preventing cardiotoxicity induced by chemotherapy of epirubicin. Furthermore, larger, placebocontrolled, perspective studies are needed to assess the efficacy of astragalus injection treatment for preventing cardiotoxicity induced by chemotherapy of epirubicin.
A retrospective observational study of biomarker levels and severity assessment in pediatric community-acquired pneumonia
Authors: Bashir Anam , Khan Raheel , Thompson Stephanie , Caceres Manuel
Published: August 2022

Multiple studies have investigated the role of biomarkers in predicting pneumonia severity in adults but minimal conclusive research exists for children. This study aimed to determine if the following biomarker levels, collected within 72 hours of hospital arrival: white blood cell count (WBC), platelet count, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-lymphocyte ratio, neutrophil count, or band count associated with community-associated pneumonia (CAP) severity in children.

Methods:

A retrospective chart review was conducted on children (aged 60 days to 18 years) diagnosed with CAP, and admitted to a regional, tertiary hospital (Charleston, WV, USA) for 3 years (2015–2018). Patients were stratified into 2 severity cohorts, mild (no ICU care), and moderate/severe (required ICU care). Biomarker values were then compared between the severity cohorts and area under the curve (AUC), and cut-off values and performance characteristics were calculated.

Results:

A total of 108 patients met inclusion criteria with 46% having moderate/severe CAP. Elevated levels of CRP (51.7 mg/L in mild vs. 104.8 mg/L in moderate/severe, P = .003, PCT (0.29 ng/ml in mild vs. 4.02 ng/mL in moderate/severe, P = .001) and band counts (8% in mild vs. 15% moderate/severe, P = .009) were associated with increased pneumonia severity. In predicting moderate/severe CAP, PCT had the highest AUC of 0.77 (P = .001) followed by bands AUC of 0.69 (P = .009) and CRP AUC of 0.67 (P = .003). Cut-off for PCT of 0.55 ng/mL had a sensitivity of 83% and a specificity of 65%. Cut-off level of 53.1 mg/L for CRP had a sensitivity of 79% and specificity of 52%. Cut off level of 12.5% bands had a sensitivity of 61% and specificity of 71%. In a multivariable model controlled for patient demographics and other biomarker levels, only PCT levels significantly predicted moderate/severe CAP (adjusted odds ratio: 1.40 [95% CI, 1.14–1.73], P = .002).

Conclusion:

Biomarkers, in particular PCT, obtained early in hospitalization may perform as possible predictors for CAP severity in children and be beneficial in guiding CAP management. However, biomarkers in pneumonia should not drive severity assessment or patient management independent of clinical presentation.
CircRNA expression profile and potential role of hsa_circ_0040039 in intervertebral disc degeneration
Authors: Huang Sheng , Zhong Junlong , Qi Qihua , Liu Gangan , Gong Ming
Published: August 2022

Purpose:

Circular RNAs (circRNAs) play an critical role in the pathological processes associated with IDD. However, the potential roles of circRNAs in IDD remain largely unclear. Here, we identify the circRNAs expression profiles and elucidate the potential role of candidate circRNAs in the pathogenesis of intervertebral disc degeneration (IDD) through microarray data and bioinformatics analyses.

Methods:

We obtained the datasets of microarrays (GSE67566 and GSE116726) from the Gene Expression Omnibus database. The differentially expressed circRNAs and miRNAs were identified using the Limma R package. The target miRNAs and target genes of the candidate circRNAs were predicted using an online tool. Functional enrichment analyses of the target genes were performed using the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed using STRING.

Results:

A total of 104 differentially expressed circRNAs were identified between the IDD and the control groups, including 41 upregulated circRNAs and 63 downregulated circRNAs (cutoff criteria (|log2 fold change| > 2, P < .05)). Hsa_circ_0040039, which was the most upregulated circRNA (log2 fold change = 2.95), was selected for further analysis. The regulatory circRNA-miRNA-mRNA network comprised hsa_circ_0040039, 2 target miRNAs (hsa-miR-424-5p and hsa-miR-15b-5p), and 77 target genes. Functional enrichment analysis showed that the 77 promising target genes are mainly enriched in the ubiquitin proteasome system and Wnt signaling pathway. Further, the PPI network showed that the top 3 hub genes are BRTC, SIAH1, and UBE2V1.

Conclusions:

A total of 104 differentially expressed circRNAs were identified between the IDD and control groups. Hsa_circ_0040039 may serve as a sponge of hsa-miR-424-5p and hsa-miR-15b-5p, to regulate the expression of downstream genes (such as BRTC, SIAH1, and UBE2V1); thus, it may be involved in IDD-associated pathological processes via the Wnt/β-catenin signaling pathway. Further studies are required to confirm the potential roles of hsa_circ_0040039 in IDD.
Rational emotive health therapy for the management of depressive symptoms among parents of children with intellectual and reading disabilities in English language
Authors: Ugwuanyi Leonard Tochukwu , Egbe Cajetan Ikechukwu , Nnamani Amuche Patricia , Ubah Josephine Chioma , Adaka Terfa Ahon , Adama Grace Ngozi , Ejide Afusat B. , Uloh-Bethels Annah Chinyeaka , Emelogu Ngozi Ugonma , Ossai Rosemary Chidimma , Okoyeukwu Ngozi Georgina , Agbo Philomina Akudo , Otu Mkpoikanke Sunday
Published: August 2022

Background:

There is little data in developing countries such as Nigeria with regard to the impact of caring for their children with intellectual and reading disability (IRD) on the quality of life of the parents and the risk of psychopathology.

Objective:

The main objective of the study was to assess the level of psychopathology, i.e., depression among parents of children with intellectual and reading disabilities.

Methods:

This was pretest/posttest control group design with 198 parents (99 fathers/99 mothers) of 100 children with the diagnosis of IRD. The measures used in this study for data collection was Beck Depression Inventory (BDI). Repeated measures analysis of variance (ANOVA) was employed for data analysis.

Results:

Result obtained showed a significant high proportion of depressive symptoms among parents of children with intellectual and reading disabilities at initial assessment. Furthermore, the REHT intervention resulted in a significant reduction in depression of parents in treatment group as compared to those in the control group.

Conclusion:

The presence of a child with intellectual and reading disabilities does not cause parents to become depressed but irrational beliefs about their children’s mental and reading deficiencies may contribute to unhealthy thinking and feelings about the future of their children. REHT is very effective in assisting depressed parents of children with intellectual and reading disabilities to think rationally about their children and work towards overcoming disability-related as well as behavior-related irrational beliefs. The mental health providers, therapists and counselors should apply the REHT in managing people with psychological distress especially parents of children with intellectual and reading disabilities who may have psychological diagnosis of depression.
Concomitant presentation of eosinophilic or oncocytic mucoepidermoid carcinoma, immunoglobulin G4–related disease, and adult-onset asthma and periocular xanthogranuloma: Case report of 3 uncommon clinical entities
Authors: Chhabra Nikita , Cebak John E. , Schmitt Alessandra , Lal Devyani , Rosenthal Allison C. , Taylor Cullen M. , Thorwarth Ryan M. , Shah Ami A. , Rodriguez-Pla Alicia
Published: August 2022

Rationale:

Immunoglobulin (Ig) G4–related disease (IgG4-RD) reportedly has a strong relationship with adult-onset asthma and periocular xanthogranuloma (AAPOX) and may be linked to sclerosing mucoepidermoid carcinoma (MEC). We present a rare case of IgG4-RD and AAPOX occurring in a patient with resected eosinophilic or oncocytic MEC.

Patient concerns:

A 52-year-old woman was referred to our rheumatology clinic in 2020 to be evaluated for suspected IgG4-RD.

Diagnoses:

The patient had diagnoses of periorbital xanthelasmas, worsening glucocorticoid-dependent chronic rhinosinusitis and adult-onset asthma, and cervical lymphadenopathy persisting 2 years after resection of a low-grade MEC of a minor salivary gland.

Interventions:

Because the patient’s symptomatic relief was glucocorticoid dependent, IgG4-RD was suspected, and she was referred to our medical center. Her amylase and lipase levels were elevated. Serum IgG4 levels were initially within normal limits, but IgG4-RD was diagnosed because of the presence of lymphadenopathy and evidence of pancreatitis, which was shown on positron emission tomography/computed tomography. Furthermore, the IgG4 levels later increased without explanation. After the patient began combination therapy with a glucocorticoid (prednisone) and methotrexate, her symptoms improved but recurred when the daily oral glucocorticoid dosage decreased below 10 mg. An excisional biopsy of her right submandibular gland in 2021 yielded results consistent with IgG4-RD. In addition, AAPOX was diagnosed, given the presence of periocular edema and plaques, adult-onset asthma, and rhinosinusitis.

Outcome:

The patient was carcinoma free at last follow-up and was receiving medication to treat the other conditions.

Lessons:

The diagnosis of these 3 concomitant, uncommon entities required approximately 7 years of medical investigations. Clinicians should know that IgG4-RD, AAPOX, and MEC may occur together.
LONG NONCODING RNA UPREGULATES ADAPTER SHCA PROTEIN EXPRESSION TO PROMOTE COGNITIVE IMPAIRMENT AFTER CARDIAC ARREST AND RESUSCITATION
Authors: Zhang Yu-Han , Peng Fei , Zhang Lu , Kang Kang , Yang Man , Chen Chan , Yu Hai
Published: August 2022

Aim: More patients are resuscitated from cardiac arrest and cardiopulmonary resuscitation (CA/CPR) due to advances in medical care. However, the burden now lies with post–cardiac arrest cognitive impairment in CA/CPR survivors. Based on our previous study, we aimed to further confirm the correlation between the long noncoding RNA-promoting ShcA (lncRNA-PS)/Src homology and collagen A (ShcA) axis and CA/CPR-induced cognitive impairment in molecular, cellular, and tissue levels. Methods and Results: The in vivo experiments were based on a mouse model of CA/CPR, while oxygen-glucose deprivation and reoxygenation was used as a cell model in vitro. Conditional ShcA suppression in neurons of the hippocampal CA1 region was achieved by cyclization recombinase of bacteriophage P1 recognizing DNA fragment locus of x-over P1 site (Cre/LoxP recombination system). Genetic manipulation of HT22 was achieved by lentivirus targeting lncRNA-PS and ShcA. Neurological function score was remarkably decreased, and cognitive function was affected after restoration of spontaneous circulation. LncRNA-PS and ShcA overexpression after CA/CPR, mainly happened in neurons of hippocampal CA1 region, was observed by in situ hybridization and immunofluorescence. Neuronal ShcA knockdown in hippocampal CA1 region before CA/CPR attenuated cognitive impairment after CA/CPR. ShcA deficiency protected HT22 cell line against oxygen-glucose deprivation and reoxygenation by inhibiting inflammation and apoptosis. In vitro upregulation of lncRNA-PS elevated ShcA expression, which was reversed by knockdown of ShcA. Conclusions: This study revealed that lncRNA-PS/ShcA axis is critically involved in the pathogenesis of cognitive impairment after CA/CPR. By inhibiting ShcA expression in neurons of the hippocampal CA1 region could improve the survival outcomes in mice after CA/CPR.
EVALUATING SEPSIS CRITERIA IN DETECTING ALTERATIONS IN CLINICAL, METABOLIC, AND INFLAMMATORY PARAMETERS IN BURN PATIENTS
Authors: Knuth Carly M. , Rehou Sarah , Barayan Dalia , Jeschke Marc G.
Published: August 2022

Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. This retrospective, single-institution cohort study aimed to increase our understanding of the septic response after burns. We hypothesized that different sepsis definitions will results in distinctive septic trajectories and biochemical patterns after injury. Sepsis was defined by our burn center–specific prospective definition, the American Burn Association criteria, Sepsis-3 criteria, and the Mann-Salinas criteria. Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre– and post–septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.
HEAD AND THORAX ELEVATION PREVENTS THE RISE OF INTRACRANIAL PRESSURE DURING EXTRACORPOREAL RESUSCITATION IN SWINE
Authors: Levy Yael , Hutin Alice , Polge Nicolas , Lidouren Fanny , Fernandez Rocio , Kohlhauer Matthias , Leger Pierre-Louis , Rambaud Jérôme , Debaty Guillaume , Lurie Keith , Ghaleh Bijan , Lamhaut Lionel , Tissier Renaud
Published: August 2022

Aim: Head and thorax elevation during cardiopulmonary resuscitation improves cerebral hemodynamics and ultimate neurological outcome after cardiac arrest. Its effect during extracorporeal cardiopulmonary resuscitation (E-CPR) is unknown. We tested whether this procedure could improve hemodynamics in swine treated by E-CPR. Methods and Results: Pigs were anesthetized and submitted to 15 minutes of untreated ventricular fibrillation followed by E-CPR. Animals randomly remained in flat position (flat group) or underwent head and thorax elevation since E-CPR institution (head-up group). Electric shocks were delivered after 30 minutes until the return of spontaneous circulation (ROSC). They were followed during 120 minutes after ROSC. After 30 minutes of E-CPR, ROSC was achieved in all animals, with no difference regarding blood pressure, heart rate, and extracorporeal membrane of oxygenation flow among groups. The head-up group had an attenuated increase in ICP as compared with the flat group after cardiac arrest (13 ± 1 vs. 26 ± 2 mm Hg at the end of the follow-up, respectively). Cerebral perfusion pressure tended to be higher in the head-up versus flat group despite not achieving statistical difference (66 ± 1 vs 46 ± 1 mm Hg at the end of the follow-up). Carotid blood flow and cerebral oxygen saturation were not significantly different among groups. Conclusion: During E-CPR, head and thorax elevation prevents ICP increase. Whether it could improve the ultimate neurological outcome in this situation deserves further investigation.
DNASE-MEDIATED DISSOLUTION OF NEUTROPHIL EXTRACELLULAR TRAPS ACCELERATES IN VITRO THROMBIN GENERATION KINETICS IN TRAUMA PATIENTS
Authors: Goswami Julie , MacArthur Taleen A. , Mahony Cillian , Kizhakkedathu Jayachandran N. , Vappala Sreeparna , Smith Stephanie , Morrissey James H. , Spears Grant M. , Bailey Kent R. , Dong Jing-Fei , Kozar Rosemary A. , Hall Nathan , Johnstone Andrea , Park Myung S.
Published: August 2022

Introduction: Neutrophil extracellular traps (NETs) trigger thrombin generation. We aimed to characterize the effects of deoxyribonuclease (DNAse) on NET components (cell-free DNA [cfDNA] and histones) and thrombin generation after trauma. Methods: Citrated plasma samples were collected from trauma patients and healthy volunteers. Thrombin generation (calibrated automated thrombogram) was measured as lag time (LT, in minutes), peak height (in nM), and time to peak thrombin generation (in minutes). Citrullinated histone 3 (CitH3) and 4 (CitH4) were measured by enzyme-linked immunosorbent assay; cfDNA by PicoGreen (all in nanograms per milliliter). Samples analyzed +/− DNAse (1,000 U/mL). Results expressed as median and quartiles [Q1, Q3], Wilcoxon testing, P < 0.05 significant. Results: We enrolled 46 patients (age, 48 [31, 67] years; 67% male) and 21 volunteers (age, 45 [28, 53] years; 43% male). Deoxyribonuclease treatment of trauma plasma led to shorter LT (3.11 [2.67, 3.52] min; 2.93 [2.67, 3.19] min), shorter time to peak thrombin generation (6.00 [5.30, 6.67] min; 5.48 [5.00, 6.00] min), greater peak height (273.7 [230.7, 300.5] nM; 288.7 [257.6, 319.2] nM), decreased cfDNA (576.9 [503.3, 803.1] ng/mL; 456.0 [393.5, 626.7] ng/mL), decreased CitH3 (4.54 [2.23, 10.01] ng/mL; 3.59 [1.93, 7.98] ng/mL), and increased H4 (1.30 [0.64, 6.36] ng/mL; 1.75 [0.83, 9.67] ng/mL), all P < 0.001. The effect of DNAse was greater on trauma patients as compared with volunteers for LT (ΔLT, −0.21 vs. −0.02 min, P = 0.007), cfDNA (ΔcfDNA −133.4 vs. −84.9 ng/mL, P < 0.001), and CitH3 (ΔCitH3, –0.65 vs. −0.11 ng/mL, P = 0.004). Conclusion: Deoxyribonuclease treatment accelerates thrombin generation kinetics in trauma patient samples as compared with healthy volunteers. These findings suggest that NETs may contribute to the hypercoagulable state observed in trauma patients.
Recent research advances in identification and prevention of youth suicide risk
Authors: Barzilay Shira , Apter Alan
Published: August 2022

Purpose of the review

The rate of youth suicidal behaviors has gradually increased over the last 15 years and continues to grow during the COVID-19 pandemic. This trend burdens mental health services and demands significant developments in risk detection and delivery of interventions to reduce the risk. In this article we outline significant advances and recent findings in youth suicide research that may facilitate strategies for identifying and preventing suicide risk among youth at risk in general and in specific risk groups.

Recent findings

The rise in suicide and suicidal behaviors is most likely to affect young people of racial, ethnic, sexual, and gender identity minorities and those living in poverty or experiencing maltreatment. The suicide rate in children is rising and demands special attention. Proximal risk factors for suicidal behavior compared with suicidal ideation have been suggested to identify near-term suicidal risk. Effective and scalable prevention strategies were identified, and the role of new technologies in suicide prevention among youth is to be determined.

To reach broader suicide prevention in youth and reduce the pressure on mental healthcare, public health approaches and improved service access for minority youth and those living in underserved areas of the world are needed.
Application of Molecular Method in Diagnosing Pediatric Sepsis
Authors: Prasetyo Dimas Seto , Karyanti Mulya Rahma , Yuniar Irene , Saharman Yulia Rosa , Holiwono Livya
Published: August 2022

Delay in detecting sepsis pathogens still become problematic issue. The gold standard for sepsis is blood culture but requires 3 days to detect definitive pathogen. Molecular methods offers rapid identification of pathogens. We evaluated the use of sepsis flow chip (SFC) assay for identifying pathogens from children with sepsis. The blood from children with sepsis were collected and incubated in the culture machine. The positive sample was subjected to amplification-hybridization using sepsis flow chip assay and culture. A total of 94 samples from 47 patients were recovered, with 25 isolates were recovered, including K. pneumoniae (11), and S. epidermidis (6). There were 24 genus/species and 18 resistance genes detected. The sensitivity, specificity, and conformity was 80%, 94.2%, and 94.68% respectively. Sepsis flow chip assay offer promising assay to identify pathogens from positive blood culture in pediatric sepsis patient and may support the antimicrobial stewardship program in hospital.
Cellulomonas palmilyticum sp. nov., from earthworm soil biofertilizer with the potential to degrade oil palm empty fruit bunch
Authors: Siriatcharanon Ake-kavitch , Sutheeworapong Sawannee , Waeonukul Rattiya , Pason Patthra , Uke Ayaka , Kosugi Akihiko , Ratanakhanokchai Khanok , Tachaapaikoon Chakrit
Published: August 2022

Oil palm empty fruit bunch (OPEFB) is lignocellulosic waste from the palm oil industry in Southeast Asia. It is difficult to degrade because of its complex matrix and recalcitrant structure. To decompose OPEFB, highly efficient micro-organisms and robust enzymatic systems are required. A bacterium with high degradation ability against untreated OPEFB was isolated from earthworm soil biofertilizer and designated as strain EW123T. Cells were Gram-stain-positive, rod-shaped and catalase-positive. In tests, the strain was negative for mycelium formation, motility, nitrate reductase and urease. The 16S rRNA gene analysis of the isolate showed 98.21 % similarity toCellulomonas udaNBRC 3747T, whereas similarity to other species was below 98 %. The genome of strain EW123Twas 3 834 009 bp long, with 73.97 mol% G+C content. Polar lipid analysis of strain EW123Tindicated phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and aminophospholipid as the lipid components of the cell wall. The major cellular fatty acid was anteiso-C15 : 0(41.26 %) and the isomer of 2,6-diaminopimelic acid (DAP) wasmeso-DAP. The average nucleotide identity value between the genome sequences of EW123TandC. udaNBRC 3747Twas 88.6 %. In addition, the digital DNA–DNA hybridization and genome average amino acid between those strains were 36.1 and 89.68 %, respectively. The ORF number (186) of carbohydrate-active enzymes, including cellulases, xylanases, mannanase, lipase and lignin-degrading enzymes, was higher than those of related strains. These results indicate that the polyphasic characteristics of EW123Tdiffer from those of other related species in the genusCellulomonas. We therefore propose a novel species of the genusCellulomonas, namelyCellulomonas palmilyticumsp. nov. (type strain TBRC 11805T=NBRC 114552T), with the ability to effectively degrade untreated OPEFB.
A large chromosomal inversion affects antimicrobial sensitivity of Escherichia coli to sodium deoxycholate
Authors: Le Vuong Van Hung , León-Quezada Rayén Ignacia , Biggs Patrick J. , Rakonjac Jasna
Published: August 2022

Resistance to antimicrobials is normally caused by mutations in the drug targets or genes involved in antimicrobial activation or expulsion. Here we show that an

Escherichia coli

strain, named DOC14, selected for increased resistance to the bile salt sodium deoxycholate, has no mutations in any ORF, but instead has a 2.1 Mb chromosomal inversion. The breakpoints of the inversion are two inverted copies of an IS5 element. Besides lowering deoxycholate susceptibility, the IS5-mediated chromosomal inversion in the DOC14 mutant was found to increase bacterial survival upon exposure to ampicillin and vancomycin, and sensitize the cell to ciprofloxacin and meropenem, but does not affect bacterial growth or cell morphology in a rich medium in the absence of antibacterial molecules. Overall, our findings support the notion that a large chromosomal inversion can benefit bacterial cells under certain conditions, contributing to genetic variability available for selection during evolution. The DOC14 mutant paired with its isogenic parental strain form a useful model as bacterial ancestors in evolution experiments to study how a large chromosomal inversion influences the evolutionary trajectory in response to various environmental stressors.
Concatenated 16S rRNA Sequence Analysis Improve Bacterial Taxonomy
Authors: Paul Bobby
Published: August 2022

Microscopic, biochemical, molecular, and computer-based approaches are extensively used to identify and classify bacterial populations. Further, advances in DNA sequencing and bioinformatics workflows facilitated sophisticated genome-based methods for microbial taxonomy. Although sequencing of 16S rRNA gene is widely employed to identify and classify the bacterial community as a cost-effective and single-gene approach. However, the accuracy of the 16S rRNA sequence-based species identification is limited by multiple copies of the gene and their higher sequence identity between closely related species. Availability of a large volume of bacterial whole-genome data provided an opportunity to develop comprehensive species-specific 16S rRNA reference libraries. With defined rules, we have concatenated four 16S rRNA gene copy variants to develop a species-specific reference library. Using this approach, species-specific 16S rRNA gene libraries were developed for four closely related Streptococcus species (S. gordonii, S. mitis, S. oralis, and S. pneumoniae). Sequence similarity and phylogenetic analysis of concatenated 16S rRNA copies yielded better resolution than single gene copy approaches. The approach is very effective to classify genetically related species, and it may reduce misclassification of bacterial species and genome assemblies.
Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: a modeling study
Authors: Li Jiahe , Champer Jackson
Published: August 2022

Wolbachia is a maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. CifA and CifB are genes found in Wolbachia phage that are responsible for cytoplasmic incompatibility, the most common type of Wolbachia reproductive interference. In this phenomenon, no viable offspring are produced when a male with both CifA and CifB (or just CifB in an alternative mechanism) mates with a female lacking CifA. Utilizing this feature, we propose new types of toxin-antidote gene drives that can be constructed with these genes. By using both mathematical and simulation models, we found that a drive containing CifA and CifB together create a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence. Our results suggest that these new types of drives based on Wolbachia transgenes are safe and flexible candidates for genetic modification of populations.
Epigenetic Changes in Saccharomyces cerevisiae Alters the Aromatic Profile in Alcoholic Fermentation
Authors: Kong Yanzhuo , Olejar Kenneth J. , On Stephen L.W. , Winefield Christopher , Wescombe Philip A. , Brennan Charles S. , Hider Richard N. , Chelikani Venkata
Published: August 2022

Epigenetic changes in genomics provide phenotypic modification without DNA sequence alteration. This study shows that benzoic acid, a common food additive and known histone deacetylase inhibitor (HDACi), has an epigenetic effect on Saccharomyces cerevisiae. Benzoic acid stimulated formation of epigenetic histone marks H3K4Me2, H3K27Me2, H3K18ac and H3Ser10p in S. cerevisiae and altered their phenotypic behavior, resulting in increased production of phenylethyl alcohol and ester compounds during alcoholic fermentation. Our study demonstrates the HDACi activity of certain dietary compounds such as sodium butyrate, curcumin and anacardic acid, suggests the potential use of these dietary compounds in altering S. cerevisiae phenotypes without altering host-cell DNA. This study highlights the potential to use common dietary compounds to exploit epigenetic modifications for various fermentation and biotechnology applications as an alternative to genetic modification. These findings indicate that benzoic acid and other food additives may have potential epigenetic effects on human gut microbiota, in which several yeast species are involved.

Importance

This manuscript investigates and reports for the first time utilizing microbial epigentics to alter the fermentation process of Pinot noir wines. We have experimentally demonstrated that certain dietary epigenetic compounds possess histone deacetylase (HDAC) inhibiting activity and can alter the wine characteristics by altering yeast gene expression. We have coined the term ‘nutrifermentics’ to represent this newly proposed field of research, which provides insights on the effect of certain dietary compounds on microbial strains and their potential application in fermentation process. This technological approach is a novel way to manipulate microorganisms for innovative food and beverage production with quality attributes.
Light prevents pathogen-induced aqueous microenvironments via potentiation of salicylic acid signaling
Authors: Lajeunesse Gaële , Roussin-Léveillée Charles , Boutin Sophie , Fortin Élodie , Laforest-Lapointe Isabelle , Moffett Peter
Published: August 2022

Upon establishment of an infection, many plant pathogens induce an aqueous microenvironment in the extracellular space of their host, resulting in water-soaked lesions. In the case of Pseudomonas syringae (Pst), this is accomplished through the activity of water-soaking effectors that stimulate abscisic acid (ABA) production and signaling, which results in stomatal closure. This reduces transpiration and induces a microenvironment favorable for bacterial growth. Stomata are also highly sensitive to environmental conditions, including light and circadian rhythm. Here, we show that a period of darkness is required for water-soaking, and that a constant light regime abrogates the water-soaking activity of Pst effectors. Additionally, we show that constant light induces resistance against Pst and that this effect requires salicylic acid (SA). An increase in SA production upon infection under constant light did not affect effector-induced ABA signaling, but rather abrogated ABA’s ability to induce stomatal closure. Indeed, under normal diurnal light regimes, application of a SA analog is sufficient to prevent the ability of the pathogen to induce stomatal closure and a water-rich niche in the apoplast. Our results provide a novel approach to interfering with a common virulence strategy, as well as providing a physiological mechanism by which SA functions in defense against certain pathogens.
Sodium regulates PLC and IP3R-mediated calcium signalling in invasive breast cancer cells
Authors: James Andrew D. , Unthank Katherine P. , Jones Isobel , Sajjaboontawee Nattanan , Sizer Rebecca E. , Chawla Sangeeta , Evans Gareth J.O. , Brackenbury William J.
Published: August 2022

Intracellular Ca2+signalling and Na+homeostasis are inextricably linked via ion channels and co-transporters, with alterations in the concentration of one ion having profound effects on the other. Evidence indicates that intracellular Na+concentration ([Na+]i) is elevated in breast tumours, and that aberrant Ca2+signalling regulates numerous key cancer hallmark processes. The present study therefore aimed to determine the effects of Na+depletion on intracellular Ca2+handling in metastatic breast cancer cell lines. The relationship between Na+and Ca2+was probed using fura-2 and SBFI fluorescence imaging and replacement of extracellular Na+with equimolar N-methyl-D-glucamine (0Na+/NMDG) or choline chloride (0Na+/ChoCl). In triple-negative MDA-MB-231 and MDA-MB-468 cells and Her2+ SKBR3 cells, but not ER+ MCF-7 cells, 0Na+/NMDG and 0Na+/ChoCl resulted in a slow, sustained depletion in [Na+]ithat was accompanied by a rapid and sustained increase in intracellular Ca2+concentration ([Ca2+]i). Application of La3+in nominal Ca2+-free conditions had no effect on this response, ruling out reverse-mode NCX activity and Ca2+entry channels. Moreover, the Na+-linked [Ca2+]iincrease was independent of membrane potential hyperpolarisation (NS-1619), but was inhibited by pharmacological blockade of IP3receptors (2-APB), phospholipase C (PLC, U73122) or following depletion of endoplasmic reticulum Ca2+stores (cyclopiazonic acid). Thus, Na+is linked to PLC/IP3-mediated activation of endoplasmic reticulum Ca2+release in metastatic breast cancer cells and this may have an important role in breast tumours where [Na+]iis perturbed.
Reduced glucosinolate content in oilseed rape (Brassica napus L.) by random mutagenesis of BnMYB28 and BnCYP79F1 genes
Authors: Jhingan Srijan , Harloff Hans-Joachim , Abbadi Amine , Welsch Claudia , Blümel Martina , Tasdemir Deniz , Jung Christian
Published: August 2022

The presence of anti-nutritive compounds like glucosinolates (GSLs) in the rapeseed meal severely restricts its utilization as animal feed. Therefore, reducing the GSL content to <18 µmol/g dry weight in the seeds is a major breeding target. While candidate genes involved in the biosynthesis of GSLs have been described in rapeseed, comprehensive functional analyses are missing. By knocking out the aliphatic GSL biosynthesis genes BnMYB28 and BnCYP79F1 encoding an R2R3 MYB transcription factor and a cytochrome P450 enzyme, respectively, we aimed to reduce the seed GSL content in rapeseed. After expression analyses on single paralogs, we used an ethyl methanesulfonate (EMS) treated population of the inbred winter rapeseed ‘Express617’ to detect functional mutations in the two gene families. Our results provide the first functional analysis by knock-out for the two GSL biosynthesis genes in winter rapeseed. We demonstrate that independent knock-out mutants of the two genes possessed significantly reduced seed aliphatic GSLs, primarily progoitrin. Compared to the wildtype Express617 control plants (36.3 µmol/g DW), progoitrin levels were decreased by 55.3% and 32.4% in functional mutants of BnMYB28 (16.20 µmol/g DW) and BnCYP79F1 (24.5 µmol/g DW), respectively. Our study provides a strong basis for breeding rapeseed with improved meal quality in the future.
A low-cost, thermostable, cell-free protein synthesis platform for on demand production of conjugate vaccines
Authors: Warfel Katherine F. , Williams Asher , Wong Derek A. , Sobol Sarah E. , Desai Primit , Li Jie , Chang Yung-Fu , DeLisa Matthew P. , Karim Ashty S. , Jewett Michael C.
Published: August 2022

Cell-free protein synthesis systems that can be lyophilized for long-term, nonrefrigerated storage and transportation have the potential to enable decentralized biomanufacturing. However, increased thermostability and decreased reaction cost are necessary for further technology adoption. Here, we identify maltodextrin as an additive to cell-free reactions that can act as both a lyoprotectant to increase thermostability, as well as a lowcost energy substrate. As a model, we apply optimized formulations to produce conjugate vaccines for ~$0.50 per dose after storage at room temperature or 37 °C for up to 4 weeks and ~$1.00 per dose after storage at 50 °C for up to 4 weeks. We show that these conjugates generate bactericidal antibodies against enterotoxigenic E. coli (ETEC) O78 O-polysaccharide, a pathogen responsible for diarrheal disease, in immunized mice. We anticipate that our lowcost, thermostable cell-free glycoprotein synthesis system will enable new models of medicine biosynthesis and distribution that bypass cold-chain requirements.