Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

Predictors of early peritoneal dialysis initiation in newborns and young infants following cardiac surgery.

OBJECTIVE: This single-centre, retrospective cohort study was conducted to investigate the predictors of early peritoneal dialysis initiation in newborns and young infants undergoing cardiac surgery. METHODS: There were fifty-seven newborns and young infants. All subjects received peritoneal dialysis catheter after completion of the cardiopulmonary bypass. Worsening post-operative (post-op) positive fluid balance and oliguria (<1 ml/kg/hour) despite furosemide were the clinical indications to start early peritoneal dialysis (peritoneal dialysis +). Demographic, clinical, and laboratory data were collected from the pre-operative, intra-operative, and immediately post-operative periods. RESULTS: Baseline demographic data were indifferent except that peritoneal dialysis + group had more newborns. Pre-operative serum creatinine was higher for peritoneal dialysis + group (p = 0.025). Peritoneal dialysis + group had longer cardiopulmonary bypass time (p = 0.044), longer aorta cross-clamp time (p = 0.044), and less urine output during post-op 24 hours (p = 0.008). In the univariate logistic regression model, pre-op serum creatinine was significantly associated with higher odds of being in peritoneal dialysis + (p = 0.021) and post-op systolic blood pressure (p = 0.018) and post-op mean arterial pressure (p=0.001) were significantly associated with reduced odds of being in peritoneal dialysis + (p = 0.018 and p = 0.001, respectively). Post-op mean arterial pressure showed a statistically significant association adjusted odds ratio = 0.89, 95% confidence interval [0.81, 0.96], p = 0.004) with peritoneal dialysis + in multivariate analysis after adjusting for age at surgery. CONCLUSIONS: In our single-centre cohort, pre-op serum creatinine, post-op systolic blood pressure, and mean arterial pressure demonstrated statistically significant association with peritoneal dialysis +. This finding may help to better risk stratify newborns and young infants for early peritoneal dialysis start following cardiac surgery.

One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.

We report the first one-pot formal alkene carboradiofluorination reaction employing easily accessible alkenes as both prosthetic group precursors and coupling partners. The methodology features rapid sequential Markovnikov-selective iodofluorination and photoinduced Pd(0/I/II)-catalyzed alkyl Heck reaction as a mild and robust fluorine-18 (18F) radiochemical approach for positron emission tomography (PET) imaging probe development. A new class of prosthetic groups for PET imaging probe synthesis was isolated as iodofluorinated intermediates in moderate to excellent yields. The one-pot formal alkenylfluorination reaction was carried out to produce over 30 analogues of a wide range of bioactive molecules. Further application of the Pd(0/I/II) manifold in PET probe development was illustrated by the direct carbo(radio)fluorination of electron-rich alkenes. The methods were successfully translated to radiolabel a broad scope of medicinally relevant small molecules in generally good radiochemical conversion. The protocol was further optimized to accommodate no-carrier-added conditions with similar efficiency for future (pre)clinical translation. Moreover, the radiosynthesis of prosthetic groups was automated in a radiochemistry module to facilitate its practical use in multistep radiochemical reactions.

Association of transcription factor 7-like 2 rs12255372 polymorphism with susceptibility of type 2 diabetes mellitus in Bangladeshi population.

Polymorphism of transcription factor 7-like 2 (TCF7L2) has a link with type 2 diabetes mellitus (T2DM) through ß cell dysfunction that causes defect in blood glucose homeostasis. This case-control study recruited 67 T2DM as cases and 65 age-matched healthy individuals as controls to determine whether the polymorphism rs12255372 (G > T) in the TCF7L2 gene have an association with T2DM in Bangladeshi population. Genomic DNA was purified from peripheral whole blood sample and direct Sanger sequencing was done for genotyping of SNP. Bivariate logistic regression was done to find out the association between genetic variant and T2DM. In our study, the minor T allele frequency was significantly more frequent in T2DM group than healthy controls (29.1% vs. 16.9%). After adjusting with confounding factors, heterozygous-genotype GT had higher odds of developing T2DM (OR 2.4; 95% CI: 1.0-5.5; p value = 0.04) and in dominant model, having SNP in TCF7L2 increased the risk of T2DM 2.3 times (95% CI: 1.0-5.2; p value = 0.04). In interaction model, genetic susceptible SNP cases interacted significantly with increasing age and BMI, female gender, and having family history of diabetes mellitus to develop T2DM (pinteraction < 0.001). Having minor T allele either in heterozygous or homozygous variant form of rs12255372 (G > T) TCF7L2 had significant association with T2DM. In conclusion, TCF7L2 gene variant increases risk of developing T2DM among the Bangladeshi population.

Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells.

Clinical and pre-clinical work for a number of cancer types has demonstrated relatively positive outcomes and effective tumour regression when the level and function of p53, a well-established tumour suppressor, is restored. Human papillomavirus (HPV)-driven cancers encode the E6 oncoprotein, which leads to p53 degradation, to allow the carcinogenic process to proceed. Indeed, there have been several attempts to revive p53 function in HPV-driven cancers by both pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyperexpressing the p53 gene promoter. Our data show that CRISPRa-mediated hyperexpression of p53 leads to HPV+ cervical cancer cell killing and the reduction of cell proliferation. This proof-of-concept data suggest that increasing p53 bioavailability may potentially be a promising therapeutic approach for the treatment of HPV-driven cancers.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

Contribution of advanced fluorescence nano microscopy towards revealing mitotic chromosome structure.

The organization of chromatin into higher-order structures and its condensation process represent one of the key challenges in structural biology. This is important for elucidating several disease states. To address this long-standing problem, development of advanced imaging methods has played an essential role in providing understanding into mitotic chromosome structure and compaction. Amongst these are two fast evolving fluorescence imaging technologies, specifically fluorescence lifetime imaging (FLIM) and super-resolution microscopy (SRM). FLIM in particular has been lacking in the application of chromosome research while SRM has been successfully applied although not widely. Both these techniques are capable of providing fluorescence imaging with nanometer information. SRM or "nanoscopy" is capable of generating images of DNA with less than 50 nm resolution while FLIM when coupled with energy transfer may provide less than 20 nm information. Here, we discuss the advantages and limitations of both methods followed by their contribution to mitotic chromosome studies. Furthermore, we highlight the future prospects of how advancements in new technologies can contribute in the field of chromosome science.

Biochemical composition of selected lines from sorghum (Sorghum bicolor L.) landraces.

MAIN CONCLUSION: Present findings revealed a great variation in protein, oil, starch, tannin and phytic acid-like biochemical attributes of sorghum genotypes. GT bi-plot analysis was used for assessment of biochemical analysis results. Sorghum is quite resistant to negative environmental conditions. Thus, it has become the basic source of nutrient in majority of developing countries. It is also used as a supporting product against several diseases. In this study, biochemical composition of new 154 sorghum lines, selected from Turkish sorghum landraces through morphological, biochemical and molecular studies, was determined. Present findings revealed based on average of two years that crude protein content of 80 lines (> 9.65%), digestible protein content of 94 lines (> 56.25%), crude oil content of 75 lines (> 3.87%), resistant starch ratio of 32 lines (> 3.93%), starch content of two lines (> 77.07%) and amylose content of 10 lines (> %25.26) were greater than standard cultivar with the greatest values and amylopectin contents of 74 lines (< 47.75%) were lower than the standard cultivar with the lowest values. As the average of years, phytic acid contents and condense tannins contents of the lines, respectively, varied between 0.02 (IS 12850/1)-6.49% (PI 177161 03/2) and 0.09 (IS 12819/1)-5.38% (PI 255738 02/3). With this study, several sorghum lines superior than the standard cultivars were identified. Those lines can be used for direct cultivar registration in short run and can be used as parent materials in further breeding studies to be conducted for various purposes in long run.

Synthesis of Copper Metal Organic Framework Based on Schiff Base Tricarboxylate Ligand for Highly Selective and Sensitive Detection of 2,4,6-Trinitrophenol in Aqueous Medium.

By using Schiff base tricarboxylate ligand 5-(4-carboxybenzylideneamino)isophthalic acid (H3CIP), a new imine functionalized copper metal organic framework (MOF) has been synthesized solvothermally. It was fully characterized by Fourier Transform Infrared (FTIR) Spectroscopy, Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS), and elemental mapping techniques. The as-synthesized MOF has been utilized as fluorescent probe for detection of nitro aromatic explosives (NAEs). The results show that the copper MOF can be developed into highly selective and sensitive sensor for detection of TNP in the aqueous medium via the "turn-off" quenching response. The linear fitting of the Stern-Volmer plot for TNP offered large quenching constant of 1.07 × 104 M-1 for Cu-MOF indicating the high sensitivity of the sensing process. Outstanding sensitivity of prepared material towards TNP detection was further validated by the low detection limit of 80 ppb (0.35 µM). The detailed mechanistic studies for their mode of action and density functional theory (DFT) calculations reveals that photo-induced electron transfer (PET) and fluorescence resonance energy transfer (FRET) processes, as well as electrostatic interactions (i.e. H-bonding) are the key factors for the turn-off response toward TNP by this fluorescent sensor. Thus, this new LMOF owing to their high water stability and remarkable functional features are potential candidates which can be developed into selective and sensitive TNP detection devices.

The effect of cleaning and repainting on the ship drag penalty.

Although the hull of a recently dry-docked large ship is expected to be relatively smooth, surface scanning and experimentation reveal that it can exhibit an "orange-peel" roughness pattern with an equivalent sand-grain roughness height ks = 0. 101 mm. Using the known ks value and integral boundary layer evolution, a recently cleaned and coated full-scale ship was predicted to experience a significant increase in the average coefficient of friction %ΔC¯f and total hydrodynamic resistance %ΔR¯T during operation. Here the report also discusses two recently reported empirical estimations that can estimate ks directly from measured surface topographical parameters, by-passing the need for experiments on replicated surfaces. The empirical estimations are found to have an accuracy of 4.5 - 5 percentage points in %ΔC¯f.

Phase-contrast 3D tomography of HeLa cells grown in PLLA polymer electrospun scaffolds using synchrotron X-rays.

Advanced imaging is useful for understanding the three-dimensional (3D) growth of cells. X-ray tomography serves as a powerful noninvasive, nondestructive technique that can fulfill these purposes by providing information about cell growth within 3D platforms. There are a limited number of studies taking advantage of synchrotron X-rays, which provides a large field of view and suitable resolution to image cells within specific biomaterials. In this study, X-ray synchrotron radiation microtomography at Diamond Light Source and advanced image processing were used to investigate cellular infiltration of HeLa cells within poly L-lactide (PLLA) scaffolds. This study demonstrates that synchrotron X-rays using phase contrast is a useful method to understand the 3D growth of cells in PLLA electrospun scaffolds. Two different fiber diameter (2 and 4 µm) scaffolds with different pore sizes, grown over 2, 5 and 8 days in vitro, were examined for infiltration and cell connectivity. After performing visualization by segmentation of the cells from the fibers, the results clearly show deeper cell growth and higher cellular interconnectivity in the 4 µm fiber diameter scaffold. This indicates the potential for using such 3D technology to study cell-scaffold interactions for future medical use.

Correction to: Determinants of exclusive breastfeeding in infants of six months and below in Malawi: a cross sectional study.

An amendment to this paper has been published and can be accessed via the original article.

Determinants of exclusive breastfeeding in infants of six months and below in Malawi: a cross sectional study.

BACKGROUND: UNICEF and WHO recommend that all children should be exclusively breastfed for the first 6 months of life as breastmilk contains all the nutrients an infant needs during this period. In Malawi, exclusive breastfeeding has been declining from 72% (2009), 70.2% (2014) and 61% in the most recent survey (2015-16). We aimed to determine factors associated with exclusive breastfeeding in Malawi. METHODS: We used data from the Malawi Demographic and Health Survey (MDHS) 2015-2016. Survey records for 2059 mothers of children aged 6 months and below were identified and potential factors influencing infant feeding were examined. Logistic regression analysis was carried out to model determinants of exclusive breastfeeding (EBF). RESULTS: EBF declined in proportion to the age of the infant. Significant associations with continuing EBF were age of the mother, ethnicity of the mother, sex of infant and number of siblings. Members of the Tumbuka (OR = 1.71, CI. 1.13-2.59) and Ngoni (OR = 2.05, CI. 1.38-3.05) communities were more likely to practice EBF. In addition, mothers with female babies (OR = 1.35, CI. 1.08-1.70) and those with 3-4 children (OR = 1.47, CI. 1.04-2.08) were more likely to engage in EBF. CONCLUSION: We identify important variations in EBF practices among population sub-groups in Malawi that need to be considered when framing health education messaging. Work is needed to assess the impact of more targeted messaging, whether delivered via 'ten steps' to successful breastfeeding under Baby Friendly Hospital Initiative (BFHI) programming or other health education and awareness campaigns to sensitize communities on implications of some cultural practices on the lives of babies. The potential role for mass media, targeted Health Surveillance Assistants' (HSA) home visits and male involvement also require exploration.

Arteriovenous Access superficialization: A New Technique and Review of Options.

BACKGROUND: Up to 30% of autogenous cephalic vein arteriovenous fistulas (AVFs) are too deep for reliable cannulation. Techniques to superficialize these AVFs have been described previously. This study describes a new surgical technique for AVF superficialization and provides a review of the alternative techniques. METHODS: The path of the fistula is marked using ultrasound, and transverse incisions are made along this path. The underlying tissue is separated from the dermis over this area to expose the fistula outflow vein. The mobilized vein is then elevated and "trapped" directly under the dermis by closing the superficial fascia and adipose tissue beneath it. RESULTS: Between March 2016 and February 2019, 23 patients underwent superficialization using this technique at two centers. The mean time between AVF creation and superficialization was 6.3 months, and the time to first use for hemodialysis after superficialization was 38.8 ± 27.9 days. The average presuperficialization depth was 7.1 ± 2.4 mm and average postsuperficialization depth was 3.7 ± 2.7 mm (P = 0.002). Sixteen fistulas were successfully accessed for a cannulation rate of 89%. 94.7% of fistulas remained patent at last visit, with only one thrombosed 8-10 weeks after superficialization. CONCLUSIONS: This technique appears to be both safe and effective, and results in a vein that is immediately subdermal without major contour deformity. Early outcomes are comparable to those alternative methods described in the literature.

Molecular insights into the regulation of rice kernel elongation.

A large number of rice agronomic traits are complex, multi factorial and polygenic. As the mechanisms and genes determining grain size and yield are largely unknown, the identification of regulatory genes related to grain development remains a preeminent approach in rice genetic studies and breeding programs. Genes regulating cell proliferation and expansion in spikelet hulls and participating in endosperm development are the main controllers of rice kernel elongation and grain size. We review here and discuss recent findings on genes controlling rice grain size and the mechanisms, epialleles, epigenomic variation, and assessment of controlling genes using genome-editing tools relating to kernel elongation.

How do office workers respond to media coverage of sitting?

BACKGROUND: Sitting time is associated with adverse physical and mental health outcomes, and premature mortality. Office workers sit for prolonged periods, so are at particular risk. Scientific advances in public health threats are predominantly communicated to the public through media reports. AIMS: This study aimed to examine office workers' impromptu responses to media coverage of scientific evidence related to the health risks of sedentary behaviour. METHODS: Semi-structured interviews were run with 26 office workers (mean age 35 years), recruited from four organizations in southern England. Within the interview, each participant provided a 'think-aloud' narrative as they read three real-world news reports relating to sedentary behaviour. Thematic analysis was conducted on verbatim transcripts. RESULTS: Three themes were extracted from the data: gauging the personal relevance of the news reports; questioning their trustworthiness and challenging the feasibility of proposed sitting-reduction strategies. Participants voiced scepticism about the applicability of the reports to their personal circumstances, and the validity of the reports and the scientific evidence underpinning them. CONCLUSIONS: Researchers, press officers and journalists should emphasise the ways in which participants in research studies represent the broader population of office workers, and offer greater transparency in reporting study methods, when reporting scientific advances in sedentary behaviour.

Role of endoscopic ultrasound-guided-fine needle aspiration biopsy in the diagnosis of lymphoma of the pancreas: A clinicopathological study of nine cases.

OBJECTIVE: Endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) is an established first-line procedure in the management of solid and cystic pancreatic masses. Lymphoma is an uncommon diagnosis in EUS-FNA of the pancreas, and it is more common for such a diagnosis to be because of secondary involvement of the pancreas by a lymphoproliferative disorder than for this to represent isolated primary pancreatic lymphoma (PPL). We present the clinical, EUS and cytological features of these lesions. MATERIAL AND METHODS: After obtaining approval from our Institutional Review Board (IRB), nine cases of lymphoma diagnosed on EUS-FNA at a tertiary care cancer centre over a period of 8 years from 2008 to 2016 were retrieved from our endoscopy and pathology archives. Rapid onsite evaluation (ROSE) was carried out by a trained cytopathologist in all these cases. Cell blocks were available in seven cases, and immunophenotyping was performed on cell blocks using the immunoperoxidase method. Flow cytometry was performed in two cases. RESULTS: The most frequent site of involvement was the head of the pancreas (n=5, 55.6%). Four out of nine cases were diagnosed as PPL (44.4%). Five cases were diagnosed as lymphoma secondarily involving the pancreas (55.6%). The most frequent diagnosis was diffuse large B-cell lymphoma (n=6, 66.7%), followed by Hodgkin's lymphoma (n=2, 22.2%) and peripheral T-cell lymphoma (n=1, 11.1%). CONCLUSION: EUS-FNA in experienced hands is a valuable diagnostic modality, in conjunction with ROSE, immunohistochemistry and flow cytometry, in the diagnosis and sub-typing of both primary and secondary pancreatic lymphoma.

Preferences regarding disclosure of prognosis and end-of-life care: A survey of cancer patients with advanced disease in a lower-middle-income country.

BACKGROUND: Cancer patients' preferences regarding disclosure of prognosis and end-of-life care remain under-reported from low- and middle-income countries where cancer poses an increasing demand on scarce healthcare resources. A better knowledge of these preferences can help in achievement of shared treatment goals. AIM: To survey preferences of adult cancer patients regarding disclosure of prognosis and end-of-life care DESIGN: A multidimensional questionnaire was developed to survey consecutively sampled patients. A fifth of the participants completed a repeat survey 3 months later. SETTING/PARTICIPANTS: Adult patients at a specialist cancer center in Pakistan. RESULTS: In total, 520 patients were surveyed initially (participation rate 98.6%) and 100 completed the repeat survey. Three in five respondents wanted a healthcare provider to give them detailed information about their prognosis and life expectancy. Those who wanted information withheld were significantly more likely to be female, to have a lower socioeconomic status, or to have lung cancer. Only two in five patients agreed that they wanted to die at home and more than 90% wanted all possible care till end-of-life. Yet, a little over half also agreed that they did not wish to be placed on a ventilator. In rank ordering preferences about end-of-life, respondents ranked "religious wellbeing" as the highest and "avoiding inappropriate prolongation of dying" as the lowest of six options. CONCLUSION: A majority of adult cancer patients surveyed in this study wanted a truthful disclosure about their disease prognosis and expressed a preference for hospital-based care at end-of-life. Healthcare providers should find ways to tailor prognostic information to patients' expressed information needs.

Does prior percutaneous endoscopic gastrostomy alter post-operative outcome after esophagectomy.

BACKGROUND: With the introduction of neoadjuvant chemoradiotherapy in patients with esophageal carcinoma, nutritional access has become essential to counter deleterious effects of dysphagia. Current NCCN guidelines do not recommend PEG prior to esophagectomy in these patients, but there is little evidence for this recommendation. The objective of this study was to compare outcomes in patients who underwent esophagectomy with or without prior PEG placement. METHODS: We retrospectively reviewed 96 patients who underwent esophagectomy between 2005 and 2012 for esophageal carcinoma. Patients were divided into two groups; Group I (PEG +ve) and Group II (PEG -ve). Patient characteristics, operative variables, and post-operative complications were compared. χ (2) and Fisher's test were used for categorical, while t test was used for interval variables. RESULTS: Median age was 51(18-70) years. Lower thoracic tumors were more common in Group I (69 vs. 63 %) (P = 0.04) and more patients underwent minimally invasive surgery in this group (50 vs. 2.6 %) (P < 0.0001). Mean blood loss (326 vs. 465 ml) (P = 0.02) and ICU stay (1.6 vs. 4.3 days) (P = 0.01) were significantly lower in Group I. There was no 30-day mortality in Group I versus 10.5 % in Group II (P = 0.01). No significant difference in anastomotic leak and stricture rate was observed. Gastric conduit was used in all patients for reconstruction. One patient had malignancy in PEG site biopsy. CONCLUSION: Percutaneous endoscopic gastrostomy before esophagectomy is safe and does not adversely impact post-operative outcomes.