bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion surgery for hepatocellular carcinoma with portal vein tumor thrombus after successful atezolizumab plus bevacizumab therapy: a case report
Authors: Hidaka Yoshifumi , Tomita Miyo , Desaki Ryosuke , Hamanoue Masahiro , Takao Sonshin , Kirishima Mari , Ohtsuka Takao
Published: July 2022

Background

The treatment of hepatocellular carcinoma (HCC) requires diverse and multidisciplinary approaches. In recent years, new agents with good antitumor effects have emerged for systemic chemotherapy, and conversion surgery (CS) after systemic chemotherapy is expected to be an effective treatment strategy for unresectable HCC. We herein report a case of unresectable HCC with portal vein tumor thrombus (PVTT) in which atezolizumab plus bevacizumab therapy induced PVTT regression, followed by CS with R0 resection.

Case presentation

The patient was a 79-year-old man with S2/S3 HCC who was referred to our department due to tumor re-growth and PVTT after two rounds of transcatheter arterial chemoembolization. The PVTT extended from the left portal vein to the main trunk, and it was determined that the resection of the left portal vein would be difficult to perform with R0 status. Based on the diagnosis of unresectable HCC, treatment with atezolizumab plus bevacizumab was initiated. After two courses of treatment, contrast-enhanced computed tomography showed that the PVTT had regressed to the peripheral side of the left portal vein, and R0 resection became possible. The patient developed grade 3 skin lesions as an immune-related adverse event, and it was determined that the continuation of chemotherapy would be difficult. Four weeks after the second course of atezolizumab plus bevacizumab administration, left lobectomy was performed. Intraoperative ultrasonography was used to confirm the location of the tumor thrombus in the left portal vein during the resection, and a sufficient surgical margin was obtained. The histopathological findings showed that primary tumor and PVTT were mostly necrotic with residues of viable tumor cells observed in some areas. The liver background was determined as A1/F4 (new Inuyama classification). The resection margins were negative, and R0 resection was confirmed. There were no postoperative complications. No recurrence was observed as of five months after surgery.

Conclusions

CS with atezolizumab plus bevacizumab therapy has potential utility for the treatment of unresectable HCC with PVTT.
Depression, aging, and immunity: implications for COVID-19 vaccine immunogenicity
Authors: Ford Bart N. , Savitz Jonathan
Published: July 2022

The aging process can have detrimental effects on the immune system rendering the elderly more susceptible to infectious disease and less responsive to vaccination. Major depressive disorder (MDD) has been hypothesized to show characteristics of accelerated biological aging. This raises the possibility that depressed individuals will show some overlap with elderly populations with respect to their immune response to infection and vaccination. Here we provide an umbrella review of this literature in the context of the SARS CoV-2 pandemic. On balance, the available data do indeed suggest that depression is a risk factor for both adverse outcomes following COVID-19 infection and for reduced COVID-19 vaccine immunogenicity. We conclude that MDD (and other major psychiatric disorders) should be recognized as vulnerable populations that receive priority for vaccination along with other at-risk groups.
Quantitative proteomic analysis shows involvement of the p38 MAPK pathway in bovine parainfluenza virus type 3 replication
Authors: Li Liyang , Li Pengfei , Chen Ao , Li Hanbing , Liu Zhe , Yu Liyun , Hou Xilin
Published: July 2022

Background

Bovine parainfluenza virus type 3 (BPIV3) infection often causes respiratory tissue damage and immunosuppression and further results in bovine respiratory disease complex (BRDC), one of the major diseases in dairy cattle, caused huge economical losses every year. However, the pathogenetic and immunoregulatory mechanisms involved in the process of BPIV3 infection remain unknown. However, the pathogenetic and immunoregulatory mechanisms involved in the process of BPIV3 infection remain unknown. Proteomics is a powerful tool for high-throughput identification of proteins, which has been widely used to understand how viruses interact with host cells.

Methods

In the present study, we report a proteomic analysis to investigate the whole cellular protein alterations of MDBK cells infected with BPIV3. To investigate the infection process of BPIV3 and the immune response mechanism of MDBK cells, isobaric tags for relative and absolute quantitation analysis (iTRAQ) and Q-Exactive mass spectrometry-based proteomics were performed. The differentially expressed proteins (DEPs) involved in the BPIV3 invasion process in MDBK cells were identified, annotated, and quantitated.

Results

A total of 116 proteins, which included 74 upregulated proteins and 42 downregulated proteins, were identified as DEPs between the BPIV3-infected and the mock-infected groups. These DEPs included corresponding proteins related to inflammatory response, immune response, and lipid metabolism. These results might provide some insights for understanding the pathogenesis of BPIV3. Fluorescent quantitative PCR and western blotting analysis showed results consistent with those of iTRAQ identification. Interestingly, the upregulated protein MKK3 was associated with the p38 MAPK signaling pathway.

Conclusions

The results of proteomics analysis indicated BPIV3 infection could activate the p38 MAPK pathway to promote virus replication.
Child and adolescent mental health services in the Western Cape Province of South Africa: the perspectives of service providers
Authors: Mokitimi Stella , Jonas Kim , Schneider Marguerite , de Vries Petrus J.
Published: July 2022

Background

Current work in the field point to the need to strengthen child and adolescent mental health services (CAMHS) globally, and especially in low- and middle-income countries (LMICs). Policy development, planning and service provision must be relevant to the needs of stakeholders at grassroots level, and should include their perspectives. This study set out to explore the perspectives and lived experiences of service providers, including their recommendations to strengthen CAMHS in South Africa.

Methods

Using focus group discussions (FGDs) and semi-structured individual interviews (SSIIs), qualitative data were collected from 46 purposefully selected multidisciplinary health service providers across the Western Cape, one of the nine provinces of South Africa. Audio-recorded data were entered into NVivo 11 (QSR), and thematic analysis was performed by two independent raters.

Results

Results highlighted a significant lack of CAMH resources, poor intersectoral collaboration, limited access to training, absence of consistency and uniformity in service delivery, weak support for staff, and high rates of negative attitudes of staff. External factors contributing to poor CAMHS identified by service providers included poor socioeconomic circumstances, high rates of HIV/AIDS, substance use and stigma. The eight recommendations to strengthen CAMHS included a need to (1) increase CAMH staffing, (2) provide dedicated CAMHS at secondary care and child-friendly infrastructure at primary care, (3) review current service focus on number of patients seen versus quality of care provided to children, (4) formalise intersectoral collaborations, (5) increase learning opportunities for trainees, (6) employ a lead professional for CAMHS in the province, (7) increase support for staff, and (8) acknowledge staff initiatives.

Conclusions

Findings underlined the need for quality improvement, standardisation and scale-up of mental health services for children and adolescents in South Africa. Whilst we used the Western Cape as a ‘case study’, we propose that our findings may also be relevant to other LMICs. We recommend that the perspectives of service users, including children and adolescents, be sought to inform service transformation.
Maternal–fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study
Authors: Sharma Ritika , Frasch Martin G. , Zelgert Camila , Zimmermann Peter , Fabre Bibiana , Wilson Rory , Waldenberger Melanie , MacDonald James W. , Bammler Theo K. , Lobmaier Silvia M. , Antonelli Marta C.
Published: July 2022

Background

Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant’s neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA.

Results

A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a ‘Fetal Stress Index’ (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file):YAP1,TOMM20andCSMD1, and two CpGs were located approximately lay at 50 kb fromSSBP4andSCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found:DAXXandARL4D.

Conclusions

Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.
Biofilm forming rhizobacteria affect the physiological and biochemical responses of wheat to drought
Authors: Karimi Esmaeil , Aliasgharzad Nasser , Esfandiari Ezatollah , Hassanpouraghdam Mohammad Bagher , Neu Thomas R. , Buscot François , Reitz Thomas , Breitkreuz Claudia , Tarkka Mika T.
Published: July 2022

Plant growth promoting rhizobacteria (PGPR) can attenuate the adverse effects of water deficit on plant growth. Since drought stress tolerance of bacteria has earlier been associated to biofilm formation, we aimed to investigate the role of bacterial biofilm formation in their PGPR activity upon drought stress. To this end, a biofilm-forming bacterial collection was isolated from the rhizospheres of native arid grassland plants, and characterized by their drought tolerance and evaluated on their plant growth promoting properties. Most bacterial strains formed biofilm in vitro. Most isolates were drought tolerant, produced auxins, showed 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity and solubilized mineral phosphate and potassium, but at considerably different levels. Greenhouse experiments with the most promising isolates, B1, B2 and B3, under three levels of water deficit and two wheat varieties led to an increased relative water content and increased harvest index at both moderate and severe water deficit. However, the bacteria did not affect these plant parameters upon regular watering. In addition, decreased hydrogen peroxide levels and increased glutathione S-transferase activity occurred under water deficit. Based on these results, we conclude that by improving root traits and antioxidant defensive system of wheat, arid grassland rhizospheric biofilm forming bacilli may promote plant growth under water scarcity.
JOSD2 regulates PKM2 nuclear translocation and reduces acute myeloid leukemia progression
Authors: Lei Hu , Yang Li , Wang Yingying , Zou Zhihui , Liu Meng , Xu Hanzhang , Wu Yingli
Published: July 2022

Pyruvate kinase M2 (PKM2) plays an important role in the metabolism and proliferation of leukemia cells. Here, we show that deubiquitinase JOSD2, a novel tumor suppressor, blocks PKM2 nuclear localization by reducing its K433 acetylation in acute myeloid leukemia (AML). Firstly, we show that JOSD2 is significantly down-regulated in primary AML cells. Reconstitute of JOSD2 in AML cells significantly inhibit cell viability and induce cell apoptosis. Next, PKM2 is identified as a novel interaction protein of JOSD2 by mass spectrometry, co- immunoprecipitation and co-immunofluorescence in HL60 cells. However, JOSD2 does not affect PKM2 protein stability. We then found out that JOSD2 inhibits nuclear localization of PKM2 by reducing its K433 acetylation modification, accompanied by decreased downstream gene expression through non-glycolytic functions. Finally, JOSD2 decreases AML progression in vivo. Taken together, we propose that JOSD2 blocks PKM2 nuclear localization and reduces AML progression.
Validity and reliability of the Turkish version of the Eating Disorder Examination Questionnaire (EDE-Q-13): short-form of EDE-Q
Authors: Esin Kübra , Ayyıldız Feride
Published: July 2022

Background

The Eating Disorder Examination Questionnaire (EDE-Q) is a frequently used scale to evaluate eating behaviors and attitudes. In recent years, its use has increased due to the fact that the use of short forms is more practical. The aim of this study was to validate the short Turkish form of the Eating Disorder Examination Questionnaire (EDE-Q) including 13 items.

Methods

The study included 924 adults at a mean age of 30.3 ± 10.93 years. EDEQ-13 was translated and adapted to Turkish according to the Beaton Guidelines. The Eating Attitudes Test-26 (EAT-26), the Satisfaction with Life Scale (SWLS), and the Body Appreciation Scale (BAS) were used to analyze their relationships to EDE-Q-13.

Results

In this study, the rate of the total variance explained by the factors of EDE-Q-13 according to the Explanatory Factor Analysis (EFA) results of the scale was 83.54%. The Cronbach's alpha value of the scale was 0.89, and the Cronbach's alpha values of the 5 subscales were calculated in the range of 0.75–0.94. The criterion validity analysis showed an acceptable correlation between EDE-Q-13 and EAT-26, SWLS, and BAS. The confirmatory factor analysis (CFA) revealed that the model had fit values that were acceptable or good.

Conclusion

Both EFA and CFA results showed that it is appropriate to use the Turkish EDE-Q-13. EDE-Q-13 was significantly correlated with eating disturbances, body appreciation, and life satisfaction. In conclusion, the Turkish version of EDE-Q-13 possesses high levels of validity and reliability.
Intratesticular versus intraperitoneal injection of Busulfan for the induction of azoospermia in a rat model
Authors: Mobarak Halimeh , Rahbarghazi Reza , Nouri Mohammad , Heidarpour Mohammad , Mahdipour Mahdi
Published: July 2022

Background

Administration of antineoplastic drugs may cause azoospermia driving to subfertility. Production of animal azoospermia models is essential for evaluating new treatment methods before therapeutic interventions in human setup. This study aimed to investigate the toxic effects of Busulfan (an anticancer drug) on some vital organs and describe the best method and appropriate dose of Busulfan to induce an animal azoospermia model.

Methods

Rats were randomly assigned into four groups, treatment groups received 10 mg/kg, 40 mg/kg Busulfan intraperitoneally (IP), 5 mg/kg Busulfan intratesticular (IT), and control group. Blood, bone marrow, liver, renal, and testes samples were collected for histological (H&E staining), biochemical (serum levels of ALT, AST, ALP, creatinine, and urea), and hematological analyses.

Results

Results revealed severe anemia and leukopenia in rats that received Busulfan via IP. By contrast, injection of 5 mg/kg Busulfan via IT did not cause anemia except with a mild decrease in RBC count. Non-significant differences in the M/E ratio were observed in all groups. The administration of 40 mg/kg of Busulfan led to evacuation and destruction in the spermatogenesis process with thin-walled seminiferous epithelium in most tubules, but in rats treated with 10 mg/kg of Busulfan, the normal spermatogenesis process was notified. IT injection of Busulfan contributed to the complete degradation of spermatogenesis in which all spermatogenic cells degenerated. In the renal tissue, hyperemia, extensive tubular necrosis degeneration, and hyaline casts were found after IP injection of Busulfan. In hepatic tissue, focal hemorrhagic, chronic cholangitis, and hepatocyte degeneration, and swelling were noticed. Biochemical analysis revealed apparent Busulfan toxicity of both hepatic and renal tissues in IP Busulfan-treated rats.

Conclusions

In summary, we found that the intratesticular injection of low doses of Busulfan (5 mg/kg) is a relatively non-invasive and safe method for producing the rat azoospermia model causing the least toxicity on vital organs.
Real-time monitoring of serotonin with highly selective aptamer-functionalized conducting polymer nanohybrids
Authors: Lim Seong Gi , Seo Sung Eun , Park Seon Joo , Kim Jinyeong , Kim Yejin , Kim Kyung Ho , An Jai Eun , Kwon Oh Seok
Published: July 2022

Adequate serotonin levels are pivotal to human well-being; thus, serotonin can be used as a biomarker because it regulates a wide range of physical and psychological functions. As an imbalance of serotonin is highly likely to initiate the pathogenesis of various disorders, monitoring serotonin levels in real time is in high demand for the early detection of disease. We fabricated a field-effect transistor (FET) biosensor based on aptamer-immobilized conducting polymer nanohybrids, which showed an instantaneous response toward serotonin in solution. The mechanism of serotonin detection was based on aptamer deformation after aptamer-ligand interaction and the consequential decrease in the charge carrier density of the FET template. Docking simulations with AutoDock/Vina and PyMOL were successfully used to investigate the binding site of serotonin in the loop structure of the aptamer. The fabricated FET template showed high sensitivity toward serotonin in the range of 10 fM to 100 nM, and the limit of detection (LOD) was exceptionally low at 10 fM. Moreover, the selectivity toward serotonin was confirmed by observing no signal after the injection of structural analogs, functional analogs and excess physiological biomolecules. The potential clinical application of this sensor was confirmed because it remained consistent when the buffer solution was exchanged for artificial serum or artificial cerebrospinal fluid (CSF). †S.G.L. and S.E.S. contributed equally to this work.
Extracellular vesicles isolated from dsRNA-sprayed barley plants exhibit no growth inhibition or gene silencing in Fusarium graminearum
Authors: Schlemmer Timo , Lischka Richard , Wegner Linus , Ehlers Katrin , Biedenkopf Dagmar , Koch Aline
Published: July 2022

Numerous reports have shown that incorporating a double-stranded RNA (dsRNA)-expressing transgene into plants or applying dsRNA by spraying it onto their leaves successfully protects them against invading pathogens exploiting the mechanism of RNA interference (RNAi). How dsRNAs or siRNAs are transferred between donor host cells and recipient fungal cells is largely unknown. It is speculated that plant extracellular vesicles (EVs) function as RNA shuttles between plants and their pathogens. Recently, we found that EVs isolated from host-induced gene silencing (HIGS) or spray-induced gene silencing (SIGS) plants contained dsRNA-derived siRNAs. In this study, we evaluated whether isolated EVs from dsRNA-sprayed barley (Hordeum vulgare) plants affected the growth of the phytopathogenic ascomycete Fusarium graminearum. Encouraged by our previous finding that dropping barley-derived EVs on F. graminearum cultures caused fungal stress phenotypes, we conducted an in vitro growth experiment in microtiter plates where we co-cultivated F. graminearum with plant EVs isolated from dsRNA-sprayed barley leaves. We observed that co-cultivation of F. graminearum macroconidia with barley EVs did not affect fungal growth. Furthermore, plant EVs containing SIGS-derived siRNA appeared not to affect F. graminearum growth and showed no gene silencing activity on F. graminearum CYP51 genes. Based on our findings, we concluded that either the amount of SIGS-derived siRNA was insufficient to induce target gene silencing in F. graminearum, indicating that the role of EVs in SIGS is minor, or that F. graminearum uptake of plant EVs from liquid cultures was inefficient or impossible.
Rescue percutaneous transhepatic portal vein embolization after failed associated liver partition and portal vein ligation for staged hepatectomy in a patient with multiple liver metastases of rectal cancer: a case report
Authors: Tomida Hidenori , Notake Tsuyhosi , Shimizu Akira , Kubota Koji , Umemura Kentaro , Kamachi Atsushi , Goto Takamune , Yamazaki Shiori , Soejima Yuji
Published: July 2022

Background

Liver metastasis is the most common form of distant spread of colorectal cancer. Despite oncological and surgical advances, only about 25% of patients are eligible to undergo resection. As the liver has a limited resectable volume, tumor reduction and remnant liver hypertrophy are of critical importance in treating initially unresectable colorectal cancer liver metastasis. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver hypertrophy within a short period and has been reported to be useful in recent years.

Case presentation

A 29-year-old woman complaining of bloody stool was referred to our hospital. She was diagnosed with rectal cancer (Rb) with simultaneous multiple liver and lung metastases. The patient was then initially commenced on chemotherapy and completed it with a satisfactory response. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant (FLR) volume was insufficient. Therefore, we decided to perform totally laparoscopic ALPPS to obtain enough FLR volume. However, the FLR increase was slow, and FLR did not attain the required volume for right trisectionectomy. Computed tomography showed that right portal venous blood flow was increased via developed collateral vessels around the portal vein. We attempted to induce further liver growth by blocking portal blood flow using additional percutaneous transhepatic portal vein embolization (PTPE), and a rapid increase in FLR was obtained. The patient underwent right trisectionectomy and partial resection of S2 with negative margins, and the patient was discharged without postoperative liver failure.

Conclusions

Resumption of the portal venous blood flow through collateral vessels after ALPPS may have interfered with the planned residual liver hypertrophy. Performing PTPE in addition to ALPPS increased the FLR volume, and radical hepatectomy was completed safely. Remnant portal venous blood flow following ALPPS is an important issue to be considered in surgical planning, and early additional portal vein embolization could be effective.
Postoperative outcomes of mepivacaine vs. bupivacaine in patients undergoing total joint arthroplasty with spinal anesthesia
Authors: Stock Laura A. , Dennis Kevin , MacDonald James H. , Goins Andrew J. , Turcotte Justin J. , King Paul J.
Published: July 2022

Background

Spinal anesthesia (SA) has been previously associated with improved outcomes after total joint arthroplasty (TJA). The purpose of this study was to compare outcomes between various local anesthetics.

Methods

This was a retrospective study of 1,328 patients undergoing primary TJA with SA from September 2020–2021 at a single institution. Patients were grouped based on TKA or THA and further separated and analyzed in terms of anesthetic agents—mepivacaine (M), hyperbaric bupivacaine (HB), or isobaric bupivacaine (IB). Subgroup analysis of same-day-discharge (SDD) patients and low- (<11 mg) and high-dose bupivacaine was performed. Statistical significance was assessed at P<0.05.

Results

Mepivacaine use was associated with younger age, lower ASAs, and lower Charlson Comorbidity Index (CCI) scores in both THAs and TKAs. Postoperatively, significant differences were found between HB, IB, and M in LOS, the first PT ambulation distance and rates of SDD, and home discharge in both THAs and TKAs. No significant differences in outcomes were observed between high- and low-dose bupivacaine in THAs or TKAs. In SDD patients, a significant difference was found only in the first 6-clicks mobility scores. After controlling for age, BMI, sex, ASA, and procedure type, mepivacaine was found to be associated with shorter LOS, increased likelihood of SDD, home discharge, POD-0 ambulation, and, further, the first ambulation distance. No significant differences were observed in 6-clicks mobility scores, urinary retention, 30-day ED returns or 30-day readmissions.

Conclusions

Both bupivacaine and mepivacaine are safe and effective local anesthetics for patients undergoing TJA as evidenced by low, similar rates of urinary retention and 30-day ED returns and readmissions. Mepivacaine does appeared to facilitate early ambulation, shorter LOS and home discharge and should be considered as the local anesthetic of choice for patients undergoing rapid recovery TJA.
Longitudinal Monitoring of Circulating Tumor DNA to Predict Treatment Outcomes in Advanced Cancers
Authors: Gouda Mohamed A. , Huang Helen J. , Piha-Paul Sarina A. , Call S. Greg , Karp Daniel D. , Fu Siqing , Naing Aung , Subbiah Vivek , Pant Shubham , Dustin Derek J. , Tsimberidou Apostolia M. , Hong David S. , Rodon Jordi , Meric-Bernstam Funda , Janku Filip
Published: July 2022

PURPOSE

The response to cancer therapies is typically assessed with radiologic imaging 6-10 weeks after treatment initiation. Circulating tumor DNA (ctDNA), however, has a short half-life, and dynamic changes in ctDNA quantity may allow for earlier assessment of the therapeutic response.

METHODS

Patients with advanced solid tumors referred to the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center were invited to participate in a liquid biopsy protocol for which serial blood samples were collected before, during, and after systemic therapy. We isolated ctDNA from serially collected plasma samples at baseline, mid-treatment, and first restaging. Genomically informed droplet digital polymerase chain reaction (ddPCR) was performed, and ctDNA quantities were reported as aggregate variant allele frequencies for all detected molecular aberrations.

RESULTS

We included 204 patients receiving 260 systemic therapies. The ctDNA detection rate was higher in progressors (patients with progressive disease) compared with nonprogressors (patients with stable disease, partial responses, or complete responses) at all time points ( P < .009). Moreover, ctDNA detection was associated with a shorter median time-to-treatment failure ( P ≤ .001). Positive delta and slope values for changes in ctDNA quantity were more frequent in progressors ( P ≤ .03 and P < .001, respectively) and were associated with a shorter median time-to-treatment failure ( P ≤ .014 and P < .001, respectively). Increasing ctDNA quantity was predictive of clinical and/or radiologic progressive disease in 73% of patients (median lead time, 23 days).

CONCLUSION

Detection of ctDNA and early dynamic changes in its quantity can predict the clinical outcomes of systemic therapies in patients with advanced solid tumors.
Effect of Liraglutide Treatment on Whole-body Glucose Fluxes in C-peptide–Positive Type 1 Diabetes During Hypoglycemia
Authors: Zenz Sabine , Regittnig Werner , Boulgaropoulos Beate , Augustin Thomas , Brunner Martina , Korsatko Stefan , Münzker Julia , Narath Sophie H , Raml Reingard , Magnes Christoph , Pieber Thomas R
Published: July 2022

Context

The effect of liraglutide in C-peptide–positive (C-pos) type 1 diabetes (T1D) patients during hypoglycemia remains unclear.

Objective

To investigate the effect of a 12-week liraglutide treatment on the body glucose fluxes during a hypoglycemic clamp in C-pos T1D patients and its impact on the alpha- and beta-cell responses during hypoglycemia.

Design

This was a randomized, double-blind, crossover study. Each C-pos T1D patient was allocated to the treatment sequence liraglutide/placebo or placebo/liraglutide with daily injections for 12 weeks adjunct to insulin treatment, separated by a 4-week washout period.

Setting and Participants

Fourteen T1D patients with fasting C-peptide ≥ 0.1 nmol/L.

Intervention(s)

All patients underwent a hyperinsulinemic-stepwise-hypoglycemic clamp with isotope tracer [plasma glucose (PG) plateaus: 5.5, 3.5, 2.5, and 3.9 mmol/L] after a 3-month liraglutide (1.2 mg) or placebo treatment.

Main Outcome Measure(s)

The responses of endogenous glucose production (EGP) and rate of peripheral glucose disposal (Rd) were similar for liraglutide and placebo treatment during the clamp.

Results

The numbers of hypoglycemic events were similar in both groups. At the clamp, mean glucagon levels were significantly lower at PG plateau 5.5 mmol/L in the liraglutide than in the placebo group but showed similar responses to hypoglycemia in both groups. Mean C-peptide levels were significantly higher at PG-plateaus 5.5 and 3.5 mmol/L after liraglutide treatment, but this effect was not reflected in EGP and Rd. Hemoglobin A1c and body weight were lower, and a trend for reduced insulin was seen after liraglutide treatment.

Conclusions

The results indicate that 3 months of liraglutide treatment does not promote or prolong hypoglycemia in C-pos T1D patients.
Cardiac Complications After 3-Column Osteotomy for Adult Spinal Deformity Patients With Formal Cardiac Clearance: Identifying Key Risk Factors and Threshold Cutoffs Via Recursive Partitioning Analysis
Authors: Lau Darryl , Haddad Alexander F. , Joshi Rushikesh S. , Deviren Vedat , Ames Christopher P.
Published: July 2022

BACKGROUND:

Despite formal cardiac clearance, a subset of 3-column osteotomy (3CO) patients still experience cardiac complications (CCs).

OBJECTIVE:

To define the incidence and risk factors for CC in 3CO patients who had formal cardiac clearance and assess the utility of the Revised Cardiac Risk Index (RCRI) and preoperative metabolic equivalent (MET) functional ability in predicting perioperative CC.

METHODS:

Patients with adult spinal deformity (ASD) who underwent 3CO deformity correction from 2006 to 2019 were retrospectively reviewed. Multivariate and recursive partitioning analyses were performed to assess risk factors.

RESULTS:

A total of 390 patients with ASD were included. The mean age was 64.6 years, and 60.3% were female. The CC rate was 9.7%. Patients with CCs were older (P < .001), had an increased history of heart disease (P = .001), and higher blood loss (P = .045). RCRI score (P = .646) or MET functional ability (P = .493) were not associated with CC. On multivariate analysis, age (P < .001), blood loss (P = .008), and prior spinal fusion (P = .025) were independent risk factors for CC. Patients age older than 81 years had a significantly higher CC rate than those younger than 81 years. In patients age 81 years and younger, if blood loss was >3900 mL, CC rate was significantly higher. Among patients age 81 years and younger and with >3900 mL blood loss, CC rate is significantly higher in patients with ejection fraction (EF) ≤54.5%.

CONCLUSION:

RCRI and MET functional ability are limited risk assessment tools in ASD 3CO patients with formal cardiac clearance. Patients older than 81 years are at high risk for CC. In younger patients, cardiac EF and blood loss are significant components to risk stratify for CC.
Co-transport of the nuclear-encoded Cox7c mRNA with mitochondria along axons occurs through a coding-region-dependent mechanism
Authors: Cohen Bar , Altman Topaz , Golani-Armon Adi , Savulescu Anca F. , Ibraheem Amjd , Mhlanga Musa M. , Perlson Eran , Arava Yoav S.
Published: July 2022

Nuclear-encoded mitochondrial protein mRNAs have been found to be localized and locally translated within neuronal processes. However, the mechanism of transport for those mRNAs to distal locations is not fully understood. Here, we describe axonal co-transport of Cox7c with mitochondria. Fractionation analysis and single-molecule fluorescence in situ hybridization (smFISH) assay revealed that endogenous mRNA encoding Cox7c was preferentially associated with mitochondria in a mouse neuronal cell line and within mouse primary motor neuron axons, whereas other mRNAs that do not encode mitochondrial protein were much less associated. Live-cell imaging of MS2-tagged Cox7c mRNA further confirmed the preferential colocalization and co-transport of Cox7c mRNA with mitochondria in motor neuron axons. Intriguingly, the coding region, rather than the 3′ untranslated region (UTR), was the key domain for the co-transport. Our results reveal that Cox7c mRNA can be transported with mitochondria along significant distances and that its coding region is a major recognition feature. This is consistent with the idea that mitochondria can play a vital role in spatial regulation of the axonal transcriptome at distant neuronal sites.
The Tunable Coupling between Metasurface and Molecular Vibration towards the Platform of Spectral Analysis
Authors: Nishijima Yoshiaki , Juodkazis Saulius
Published: July 2022

We have demonstrated the coupling of metasurface resonance with a molecular vibration from weak to strong. Metal-insulator-metal (MIM) metasurfaces using various polymers as the insulator layer (I-layer) were fabricated and characterised. The strength of coupling between MIM metasurface and molecular absorbance in the I-layer of organic nano-film depends on the dipole mode of the molecular vibration and the molecular number density. In the case of strong coupling, when Rabi-splitting is observed at the molecular absorption band, the coupling efficiency reaches several percent of the particular molecular vibration modes in the volume below nanodisks of the MIM metasurface.
Control moment gyroscope singularity avoidance for agile spacecraft
Authors: Παπακωνσταντίνου Χαράλαμπος
Published: July 2022

Μετά την εκτόξευση του πρώτου τεχνητού δορυφόρου στις 4 Οκτωβρίου 1957 υπό την ηγεσία του, Ουκρανού μηχανικού πυραύλων, Σεργκέι Κορολιόφ, ακολούθησε η κατασκευή και εκτόξευση μιας πληθώρας δορυφόρων. Με την ανάπτυξη ενός τυ- ποποιημένου μοντέλου για την κατασκευή μικρών δορυφόρων το 1999, οι CubeSats έγιναν ευρέως διαδεδομένοι εξαιτίας του χαμηλού κόστους κατασκευής τους και της δυνατότητας τους να εκτελούν πολυάριθμες εργασίες. Σε μια εποχή που βασίζεται ολοένα και περισσότερο στα δεδομένα, όσο περισσότερα δεδομένα συλλέγει ένας δο- ρυφόρος σε συγκεκριμένο χρόνο, τόσο πιο χρήσιμος είναι. Η ζήτηση για ταχύτητα μεταφράζεται σε απαίτηση για την ανάπτυξη ενός συστήματος ικανού να παρέχει την επιθυμητή ευελιξία.Οι γυροσκοπικοί επενεργητές ελέγχου (ΓΕΕ) είναι γνωστοί ως ενεργοποιη- τές/επενεργητές υψηλής ροπής ενώ παράλληλα προσφέρουν μικρή μάζα, όγκο, και χαμηλή ισχύ. Το κύριο πρόβλημα των ΓΕΕ είναι αυτό των ενικοτήτων. Αυτή η δια- τριβή λαμβάνει υπόψιν το πρόβλημα των ενικοτήτων προτείνοντας νέες μεθόδους για την καθολική καθοδήγηση του συστήματος τεσσάρων ΓΕΕ σε διαμόρφωση πυραμί- δας. Αρχικά, παρουσιάζεται ένας αλγόριθμος βελτιστοποίησης με στόχο την εύρεση διαδρομών χωρίς ενικότητες, ο οποίος μπορεί να χρησιμοποιηθεί για εφαρμογές σχε- δόν πραγματικού χρόνου. Σε συνδυασμό με μια τεχνική μεταβλητής αναζήτησης, οι υπολογιστικές απαιτήσεις της προτεινόμενης μεθόδου μπορούν να προσαρμοστούν στις απαιτήσεις της επιθυμητής εφαρμογής. Η καθολική καθοδήγηση εξετάζεται στη συνέχεια από την προοπτική της Μηχανικής Μάθησης (ΜΜ). Σε σύγκριση με τις περισσότερες από τις τρέχουσες μεθόδους, αποδεικνύεται ότι η χρήση ενός συστή- ματος ΜΜ μπορεί να αλλάξει δραματικά τον έλεγχο των ΓΕΕ και τον χειρισμό των ενικοτήτων.Εκτός από τις μεθόδους που βασίζονται στο λογισμικό, περιγράφεται μια νέα προσέγγιση βασισμένη στο υλικό. Ένας καινοτόμος σχεδιασμός του συστήματος των τεσσάρων ΓΕΕ, που ονομάζεται περιστρεφόμενο σύστημα τεσσάρων ΓΕΕ, παρουσιά- ζεται μαζί με τον νόμο ελέγχου του και προσφέρει δυνατότητες παρόμοιες με αυτές του συστήματος τεσσάρων ΓΕΕ μεταβλητής ταχύτητας αλλά με χαμηλότερη ισχύ και πολυπλοκότητα. Τέλος, ένα εξαιρετικά μικρού μεγέθους σύστημα τεσσάρων ΓΕΕ σε διαμόρφωση πυραμίδας κατασκευασμένο από έτοιμα/εμπορικά εξαρτήματα όσο και ένα ρουλεμάν αέρα κατασκευασμένο αποκλειστικά από τρισδιάστατα εκτυπωμένα υλικά αποδεικνύουν ότι είναι εφικτή η κατασκευή μιας ιδιαίτερου χαμηλού κόστους και ελαφριάς πλατφόρμας για τη δοκιμή νάνο-ΓΕΕ.
The genome sequence of the dun-bar pinion, Cosmia trapezina (Linnaeus, 1758)
Authors: Boyes Douglas ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Godfray Charles , Holland Peter W. H. ,   Darwin Tree of Life Consortium
Published: July 2022

We present a genome assembly from an individual male Cosmia trapezina (dun-bar pinion; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 825 megabases in span. The majority of the assembly (99.87%) is scaffolded into 32 chromosomal pseudomolecules with the Z chromosome assembled. The complete mitochondrial genome was also assembled and is 15.4 kilobases in length.
LIBYA'S FOREIGN TRADE WITH EUROPEAN UNION COUNTRIES
Authors: Elbashir Rania
Published: July 2022

The subject of this empirical and theoretical work is the exchange of foreign trade in Libya with the countries of the European Union. The scientific objective of the research is to make a scientific classification of the volume of foreign trade between Libya and the European Union countries and to discover the factors that hinder foreign trade and explain them scientifically. European countries also support this cooperation and contribute significantly to the formulation of future cooperation policies with Libya in various social, political, and economic fields. However, this cooperation takes place in light of objective difficulties arising from the conflicting interests of Western countries in North Africa and Libya. Since these relations are burdened with many problems of different nature, we started this paper from two assumptions: The first premise is that in the trade relations between Libya and the European Union, there are common interests for foreign trade that are more feasible. The second premise is that more encouragement and protection for investments by the countries of the European Union helps in new qualitative development and economic growth in Libya, which will significantly improve trade relations between Libya and the countries of the European Union.
ELEUTHERIC-CONJECTURAL LIBERTARIANISM: A CONCISE PHILOSOPHICAL EXPLANATION
Authors: Lester J. C.
Published: July 2022

The two purposes of this essay. The general philosophical problem with most versions of social libertarianism and how this essay will proceed. The specific problem with liberty explained by a thought-experiment. The positive and abstract theory of interpersonal liberty-in-itself as ‘the absence of interpersonal initiated constraints on want-satisfaction’, for short ‘no initiated imposed costs’. The individualistic liberty-maximisation theory solves the problems of clashes, defences, and rectifications without entailing libertarian consequentialism. The practical implications of instantiating liberty: three rules of liberty-in-practice, 1) initial ultimate control of one’s body, 2) initial ultimate control of one’s used resources, 3) consensual interpersonal interactions and resource transfers. These rules are economically efficient and maximise general want-satisfaction. Private property and legal remedies are additional practical institutional aspects, but to which ‘initiated imposed costs’ then apply prima facie. Libertarian law is often mistaken for complete libertarianism. Moral explanations are a separate issue. The three main moral theories imply libertarianism, but it can be morally posited independently of them. Critical rationalism and its application. No empirical or argumentative support for theories. An important ambiguity with ‘justification’. How the epistemology applies to the theory of liberty and its application but remains separable in principle. Conclusion: there are further published explanations but this should be enough to generate useful criticism. Appendix replying to some typical comments.
A CRITIQUE OF “A CRITIQUE OF LESTER’S ACCOUNT OF LIBERTY”: A REPLY TO FREDERICK 2013
Authors: Lester J. C.
Published: July 2022

Frederick 2013 (the critique) offers criticisms of the Escape from Leviathan (EfL) theory of libertarian liberty and also of its compatibility with preference-utilitarian welfare and private-property anarchy. This reply to the critique first explains the underlying philosophical problem with libertarian liberty and EfL’s proposed solution in a concise and precise way. It then goes through the critique in detail showing that it does not grasp the problem or the solution and offers only misrepresentations and unsound criticisms. 1. What the “compatibility thesis” really states. 2. What “initiated imposed costs” really are. 3. Paradoxes solved. 3.1 Why the forced reduction of the population would not increase liberty. 3.2 Why illiberal measures would not increase liberty. 4. How liberty relates to property. 4.1 How liberty relates to self-ownership. 4.2 How liberty relates to initial acquisition. 5. How liberty relates to free markets. 6. Understanding the solution requires a prior understanding of the problem.
Rationale for the Need to Transform the Accounting System
Authors: Mislavskaya N.
Published: July 2022

The article analyzes the conditions for the functioning of the modern economy. The author comes to the conclusion that there is a high level of uncertainty in the implementation of economic activities against the background of standard and unique economic risks, as well as the presence of probabilistic events. As a tool to reduce the level of uncertainty, it is proposed to use a system of accounting and accounting (financial) reporting with an emphasis on unification of accounting methodology and accounting methods, as well as refusal to comply with the requirements of international financial reporting standards.
Individual Educational Route As a Means of Developing Digital Competence of University Library Staff
Authors: Babina Ol'ga , Ermolovich E.
Published: July 2022

The problem of determining the structure and content of the professional competence of library specialists in the context of digitalization is becoming more and more urgent and does not find its solution due to the lack of a valid professional standard for a specialist in library and information activities. The need to clearly describe the structure of the digital competence of the modern librarian, as well as how to develop it, determined the problems of this article.

The methodological and theoretical basis of this study was compiled by leading theories and scientific schools on a competent approach, set forth in the works of domestic and foreign scientists.

The paper describes the structure of digital competence of the university library staff, which includes cognitive, functional-activity, motivation-value and communicative components. The organizational and methodological conditions for the development of digital competence among the staff of the university library are justified and described. The authors developed the contents of educational routes built taking into account the specifics of the digital activities of the categories of university employees.
Monitoring Learning Outcomes in the Virtual Environment Moodle
Authors: Burmistrova Nataliya , Ilina N. , Kornilceva E. , Shamis V. , Shmakova A.
Published: July 2022

The authors investigate the problem of monitoring learning outcomes, which contributes to improving the quality of training of university graduates. The tools of the Moodle e-learning environment to monitor learning activity of students are considered. The possibilities that Moodle services provide to the teacher to improve the quality of course resources, as well as the effectiveness of student learning are identified. The Moodle educational environment (modular object-oriented dynamic learning environment) is a free learning management system focused primarily on interaction between the teacher and students, although it is also suitable for conducting traditional distance courses, as well as supporting in-person training. The study shows that by means of Moodle, a teacher can create courses, filling them with content in the form of texts, auxiliary files, presentations, questionnaires, tests, etc. As a part of the study, the authors created an electronic training course “Fundamentals of Financial Computing” with an emphasis on the use of the interactive control and measurement complex of the development of the discipline. The monitoring of students’ cognitive potential as a component of mathematical competence was carried out. The results of pedagogical measurements are presented, which demonstrate the positive dynamics of the quality of subject education in the conditions of informatization of life spheres.
Journal scan
Authors: Welyczko Nikki
Published: July 2022

An overview of recently published articles on Clostridium C. difficile infection, inflammatory bowel disease and bariatric surgery.
Research round-up
Authors: Jack Kathryn
Published: July 2022

A brief overview of recently published articles on liver disease
NDV as an Oncolytic Agent - Study in Cancer Cell Lines
Authors: Pathak Upasana , Malik Nagesh , Pal R. B.
Published: July 2022

Newcastle disease virus (NDV) exhibits oncolysis in its natural form. This oncolytic virus (OV) has the potential to specifically infect, propagate, and lyse cancer cells while sparing the normal cells. This study was aimed to screen for oncolytic NDV strain isolated from poultry. A total of ten velogenic NDV strains were propagated in 10 day old embryonated SPF chicken eggs and allantoic fluid of these infected eggs was collected for further study. The virus enumeration was carried out by hemagglutination assay (HA) and end point dilution method. The cytopathic effect of ten NDV strains on cancer cell lines like MDA-MB-231, MCF-7, PC3, and A549 along with normal control cell line HEK293 was determined by MTT assay 72 hours post infection. These cell lines were infected with three doses (1, 0.1, and 0.01 MOI). DNA laddering effect of the screened NDV isolate was studied after infecting all cancer and normal cells at MOI 1. Morphological changes in MDA-MB-231 on infection with the screened NDV isolate were analyzed using H&E hematoxylin and eosin staining. The screened NDV isolate showed the maximum cytopathic effect i.e. 61.55% on MDA-MB-231 at MOI 1 but had no potent cytotoxic effect on HEK293. DNA laddering effect was observed which confirmed the mode of death to be apoptosis. All the observed morphological changes in MDA-MB-231 were typical of the cytopathogenic effects of NDV on cancer cell lines. In conclusion, the screened oncolytic NDV shows effective oncolysis against MDA-MB-231 cell line. However, further study is required to determine the exact mode of action involved.