The Hammersmith Score Optimises Patient Selection and Predicts for Overall Survival in Early-Phase Cancer Trial Participants Independent of Tumour Burden.

INTRODUCTION: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication are paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (albumin <35 g/L, lactate dehydrogenase >450 IU/L, sodium <135 mmol/L), is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and C-index was used to compare predictive ability of prognostic models. RESULTS: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS, and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95% CI: 1.01-6.24, p = 0.049; HS 2/3 vs. 0: 10.32, 95% CI: 2.15-49.62, p = 0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95% CI: 1.12-26.57, p = 0.036; RMS 3 vs. 0/1 6.83, 95% CI: 1.15-40.53, p < 0.001; C-index 0.743). CONCLUSIONS: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

The oral microbiome of treated and untreated chronic HCV infection: A preliminary study.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. MATERIALS AND METHODS: This case-control preliminary study enrolled three equal groups: Group (I): untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. RESULTS: The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and the healthy ones. CONCLUSIONS: Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.

ZnO Nanorods Coated Single-Mode-Multimode-Single-Mode Optical Fiber Sensor for VOC Biomarker Detection.

This work demonstrated a ZnO-coated optical fiber sensor for the detection of a volatile organic compound (VOC) biomarker for diabetes for detecting isopropanol (IPA) markers. A coreless silica fiber (CSF) was connected to a single-mode fiber (SMF) at both ends to achieve a SMF-CSF-SMF structure. CSF is the sensing region where multimode interference (MMI) generates higher light interaction at the interface between the fiber and sensing medium, leading to enhanced sensitivity. Optimization of the CSF length was conducted numerically to attain the highest possible coupling efficiency at the output. Surface functionalization was achieved via hydrothermal growth of ZnO nanorods directly onto the CSF at low temperatures. The optical fiber-based sensor was successfully fabricated and tested with 20%, 40%, 60%, 80%, and 100% of IPA. The sensor response was recorded using an optical spectrometer and analyzed for sensor sensitivity. The fabricated sensor shows the potential to detect isopropanol with the sensitivity of 0.053 nm/%IPA vapor. Further improvement of the sensor sensitivity and selectivity is also proposed for future work.

Transcriptomic Responses to Coaggregation between Streptococcus gordonii and Streptococcus oralis.

Cell-cell adhesion between oral bacteria plays a key role in the development of polymicrobial communities such as dental plaque. Oral streptococci such as Streptococcus gordonii and Streptococcus oralis are important early colonizers of dental plaque and bind to a wide range of different oral microorganisms, forming multispecies clumps or "coaggregates." S. gordonii actively responds to coaggregation by regulating gene expression. To further understand these responses, we assessed gene regulation in S. gordonii and S. oralis following coaggregation in 25% human saliva. Coaggregates were formed by mixing, and after 30 min, RNA was extracted for dual transcriptome sequencing (RNA-Seq) analysis. In S. oralis, 18 genes (6 upregulated and 12 downregulated) were regulated by coaggregation. Significantly downregulated genes encoded functions such as amino acid and antibiotic biosynthesis, ribosome, and central carbon metabolism. In total, 28 genes were differentially regulated in Streptococcus gordonii (25 upregulated and 3 downregulated). Many genes associated with transporters and a two-component (NisK/SpaK) regulatory system were upregulated following coaggregation. Our comparative analyses of S. gordonii-S. oralis with different previously published S. gordonii pairings (S. gordonii-Fusobacterium nucleatum and S. gordonii-Veillonella parvula) suggest that the gene regulation is specific to each pairing, and responses do not appear to be conserved. This ability to distinguish between neighboring bacteria may be important for S. gordonii to adapt appropriately during the development of complex biofilms such as dental plaque. IMPORTANCE Dental plaque is responsible for two of the most prevalent diseases in humans, dental caries and periodontitis. Controlling the formation of dental plaque and preventing the transition from oral health to disease requires a detailed understanding of microbial colonization and biofilm development. Streptococci are among the most common colonizers of dental plaque. This study identifies key genes that are regulated when oral streptococci bind to one another, as they do in the early stages of dental plaque formation. We show that specific genes are regulated in two different oral streptococci following the formation of mixed-species aggregates. The specific responses of S. gordonii to coaggregation with S. oralis are different from those to coaggregation with other oral bacteria. Targeting the key genes that are upregulated during interspecies interactions may be a powerful approach to control the development of biofilm and maintain oral health.

Efficacy of two-week therapy with doxycycline-based quadruple regimen versus levofloxacin concomitant regimen for helicobacter pylori infection: a prospective single-center randomized controlled trial.

BACKGROUND: Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population. SETTINGS AND DESIGN: An open-label, randomised, parallel, superiority clinical trial. METHODS: We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment. RESULTS: Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454-4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394-3.774]. We didn't report serious adverse effects. CONCLUSIONS: Levofloxacin concomitant therapy wasn't superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population. TRIAL REGISTRATION: We registered this study as a standard randomized clinical trial ( Clinicaltrial.gov , identifier- NCT04348786 , date:29-January-2020).

Extension of Iliac Branch Device Repair Into the Superior Gluteal Artery Is a Safe and Effective Maneuver.

BACKGROUND: In some cases of complex aortoiliac endovascular repair, the hypogastric landing zone is suboptimal or even insufficient. This study aimed at the technical feasibility and at the outcome of iliac branch device (IBD) deployment with extension of the IBD into the superior gluteal artery (SGA). MATERIALS AND METHODS: This study involves a retrospective analysis of a prospectively maintained single-center cohort of patients with implantation of IBD for aortoiliac and postdissection aneurysms. The IBD cohort with landing zones in the hypogastric main trunk (IIA IBD) was compared with the IBD cohort with landing zones in the SGA (SGA IBD). The main outcome parameters were primary technical success, patency of the hypogastric branch, and freedom from IBD-specific secondary interventions within 30 days. Other outcomes of interest were long-term patency and freedom from buttock claudication, as well as the incidence of endoleaks. Group comparisons were made by univariate significance tests, and freedom from reintervention was analyzed with the Kaplan-Meier-method. RESULTS: From January 2015 to October 2017, a total of 46 IBDs were implanted in 40 patients (39 male; mean age, 71.9 ± 9.1 years). Nineteen of 46 (41.3%) IBDs were extended with at least one bridging stent graft into the SGA because of aneurysmal or short internal iliac artery (IIA). Technical success was achieved in 97.8% (96.3% for IIA IBD vs. 100% for SGA IBD, P = 0.163), and the primary ipsilateral limb patency rate was 100% within 30 days after the procedure. During a mean follow-up period of 19.8 ± 10.0 months (24.7 ± 10.8 for IIA IBD vs. 25.1 ± 9.8 for SGA IBD, P = 0.461), 11.1% IBDs in the IIA IBD group and 15.8% IBDs in the SGA IBD group needed secondary interventions (P = 0.33). Follow-up revealed no patients suffering from persistent buttock claudication or erectile dysfunction. One patient in the SGA IBD group died at late follow-up from a non-aneurysm-related cause. CONCLUSIONS: Extension of IBD into the SGA is a technically feasible and safe maneuver in the treatment of aortoiliac aneurysms with outcomes comparable to those when IBDs extend to the main trunk of the hypogastric artery.

Single-step 3D-printed integrated optical system and its implementation for a sensing application using digital light processing technology.

This study proposes a single-step integrated optical fabrication scheme utilizing a 3D printer using digital light processing technology. Strong light confinement in the fabricated structure is realized through the introduction of an elevated (tower-shaped) waveguide in a transparent photosensitive resin (PX-8880). The fabrication is optimized to maximize light confinement through varying the dimensions of the guiding region and the tower structure. Benefiting from the surface roughness produced by the slicing process in the 3D printing (50 µm resolution), the fabricated structure was tested for vapor sensing. Obvious intensity dynamics have been reported due to the change of the optical scattering due to the presence of vapor as well as polymer vapor interaction. Though the reported response time is long, further optimization can lead to practical operation time.

An Analytical Model for Describing the Power Coupling Ratio between Multimode Fibers with Transverse Displacement and Angular Misalignment in an Optical Fiber Bend Sensor.

The power coupling ratio between step-index multimode fibers caused by combined transversal and angular misalignment is calculated. A theoretical description of the coupling efficiency between two optical fibers based on geometrical optics is provided. The theoretical calculations are collaborated by experiments, determining the power coupling ratio between three output fibers with an axial offset and angular misalignment with a single input fiber. The calculation results are in good agreement with experimental results obtained using a previously fabricated optical fiber sensor for monitoring physiological parameters in clinical environments. The theoretical results are particularly beneficial for optimizing the design of optical fiber bending sensors that are based on power coupling loss (intensity) as the measurement interrogation requires either axial displacement, angular misalignment, or both.

Synthesis and biological evaluation of new oxopyrrolidine derivatives as inhibitors of acetyl cholinesterase and ß amyloid protein as anti - Alzheimer's agents.

A new series of oxopyrrolidines was synthesized and evaluated for their effect on Alzheimer's disease by measuring their inhibitory activity against acetyl cholinesterase enzyme and amyloid ß 42 protein. Most of the compounds showed good inhibitory activity with ethyl 2-(2-(2, 6-dimethylphenylcarbamoyl)- 5-oxopyrrolidin-1-yl) acetate (V) having the highest activity against acetyl cholinesterase with IC50 value 1.84 ng/g tissue compared to standard donepezil 3.34 ng/g tissue. Furthermore, compound 1-((4-(4-chlorophenyl) piperazin-1-yl) methyl)-N-(2,6-dimethylphenyl)-5- oxopyrrolidine- 2-carboxamide (IIIe) displayed the highest activity against ß 42 protein with IC50 value of 11.3 Pg/g tissue compared to 18.4 Pg/g tissue of donepezil.

Transformation optics based on unitary vectors and Fermat's principle for arbitrary spatial transformation design.

A methodology of designing an arbitrary transformation using transformation optics (TO) based on unitary vectors and Fermat's principle is presented. The TO equation is derived in terms of grid coordinates. The geometry of the transformed space is stored in the grid coordinates rather than the transformation functions. This allows the crafting of an arbitrary transformation by combining several transformation templates together. The touch interface is employed to intuitively apply the transformations. The resulting material parameters are calculated from the proposed method and verified using the anisotropic finite-difference frequency-domain method. Five examples are presented to demonstrate the capability of this method.

Differential impact of smoking on mortality and kidney transplantation among adult Men and Women undergoing dialysis.

BACKGROUND: The extent to which smoking contributes to adverse outcomes among men and women of all ages undergoing dialysis is uncertain. The objective of this study was to determine the differential impact of smoking on risks of mortality and kidney transplantation by age and by sex at dialysis initiation. METHODS: We conducted a population-based cohort of incident U.S dialysis patients (n = 1, 220, 000) from 1995-2010. Age- and sex-specific mortality and kidney transplantation rates were determined for patients with and without a history of cardiovascular disease. Multivariable Cox regression evaluated relative hazard ratios (HR) for death and kidney transplantation at 2 years stratified by atherosclerotic condition, smoking status and age. Analyses were adjusted for demographic characteristics, non-cardiovascular conditions, laboratory variables, socioeconomic and lifestyle factors. RESULTS: The average age was 62.8 (±15) years old, 54 % were male, and the majority was white. During 2-year follow-up, 40.5 % died and 5.7 % were transplanted. Age- and sex-specific mortality rates were significantly higher while transplantation rates were significantly lower for smokers with atherosclerotic conditions than non-smokers (P < 0.01). The adjusted mortality hazards were significantly higher for smokers with pre-existing coronary disease (HR 1.15, 95 % CI (1.11-1.18), stroke (HR 1.21, 1.16-1.27) and peripheral vascular disease (HR = 1.21, 1.17-1.25) compared to non-smokers without these conditions (HR 1.00, referent group). The magnitude of effect was greatest for younger patients than older patients. Contrastingly, the adjusted risks of kidney transplantation were significantly lower for smokers with coronary disease: (HR 0.60, 0.52-0.69), stroke; (HR 0.47, 0.37-0.60), and peripheral arterial disease (HR 0.55, 0.46-0.66) respectively compared to non-smokers without these conditions. CONCLUSIONS: We provide compelling evidence that smoking is associated with adverse clinical outcomes and reduced lifespans among dialysis patients of all ages and sexes. The adverse impact is greatest for younger men and women.

Optimization of a horizontal slot waveguide biosensor to detect DNA hybridization.

A full-vectorial H-field formulation-based finite element approach is used to optimize a biosensor structure incorporating a horizontal slot waveguide. It is designed to detect DNA hybridization through the change of the effective index of the waveguide structure. The key parameters, such as normalized power confinement, power density, change in effective index, and sensitivity are presented by optimizing the device parameters of the slot waveguide. It is shown here that a 90.0 µm long compact Mach-Zehnder section can be designed with horizontal slot waveguide to detect DNA hybridization and for a ring resonator arrangement a sensitivity of 893.5 nm/RIU is obtained.

Simultaneous dispersion measurements of multiple fiber modes using virtual reference interferometry.

We present the simultaneous measurement of first and second order dispersion in short length (< 1 m) few mode fibers (polarization and transverse) using virtual reference interferometry. This technique generates results equivalent to balanced spectral interferometry, without the complexity associated with physical balancing. This is achieved by simulating a virtual reference with a group delay equal to that of the physical interferometer. The amplitude modulation that results from mixing the interferograms, generated in both the unbalanced interferometer and the virtual reference, is equivalent to the first order interference that would be produced by physical balancing. The advantages of the technique include speed, simplicity, convenience and the capability for simultaneous measurement of multiple modes. The theoretical framework is first developed and then verified experimentally.

Characterizing short dispersion-length fiber via dispersive virtual reference interferometry.

The ability to characterize fibers with near-zero dispersion-length products is of considerable practical interest. We introduce dispersive virtual reference interferometry (DVRI) as a technique for the characterization of short length (<1m) fibers with near-zero disperison-length. DVRI has an accuracy equivalent to standard balanced spectral interferometry (on the order of 10(−3) ps and 10(−5) ps/nm for the group delay and dispersion-length measurements respectively) but does not require wide spectral bandwidths or multiple spectral scans. Following experimental validation, the DVRI technique is used to characterize a 23.3-cm erbium-doped gain fiber (dispersion-length product <0.002 ps/nm), using a tunable laser with a bandwidth of 145 nm. Furthermore, the dispersion in a 28.6-cm commercial dispersion shifted fiber is characterized across the zero-dispersion wavelength and the zero-disperison-wavelength and slope were determined to be 1566.7 nm and 8.57 × 10(−5) ps/(nm2∙m) with a precision of ± 0.2 nm and ± 0.06 × 10(−5) ps/(nm2∙m), respectively.

Realization of a polymer nanowire optical transducer by using the nanoimprint technique.

An optical transducer using an integrated optics polymer nanowire is proposed. The nanoimprint technique is used to fabricate an OrmoComp nanowire with 1.0 µm width and 0.5 µm height, but the resulting sidewalls are not perfectly vertical. Maximum sensitivity is achieved by enhancing the evanescent field in the cladding region. The possible mode fields and power confinement of the nanowire are studied with respect to their structural dimensions, the operating wavelength, and the cladding material by using the H-field finite element method. The attenuation coefficient is extracted and calculated over the different cladding media, specifically air, water, and glycerol solution. It is observed that the scattering caused due to the surface roughness is the dominant effect that provides a larger attenuation coefficient.

Stability and photocurrent enhancement of photodetectors by using core/shell structured CsPbBr3/TiO2 quantum dots and 2D materials.

Ultra-stable CsPbBr3 perovskite quantum dots (QDs) were prepared, and the performance of the photodetector fabricated from them was enhanced by 2D material incorporation. This multi-component photodetector appears to have good stability in the ambient utilization environment. All inorganic CsPbBr3 QDs are potential candidates for application in photodetection devices. However, QDs have several issues such as defects on the QD surface, degradation under environmental conditions, and unfavorable carrier mobility limiting the high performance of the photodetectors. This work addresses these issues by fabricating a core/shell structure and introducing 2D materials (MXenes, Ti3C2Tx) into the device. Here, three types of photodetectors with QDs only, QDs with a core/shell structure, and QDs with a core/shell structure and MXenes are fabricated for systematic study. The CsPbBr3/TiO2 photodetector demonstrated a two times photocurrent enhancement compared to bare QDs and had good device stability after TiO2 shell coating. After introducing Ti3C2Tx into CsPbBr3/TiO2, a significant photocurrent enhancement from nanoampere (nA) to microampere (µA) was observed, revealing that MXenes can improve the photoelectric response of perovskite materials significantly. Higher photocurrent can avoid signal interference from environmental noise for better practical feasibility. This study provides a systematic understanding of the photocurrent conversion of perovskite quantum dots that is beneficial in advancing optoelectronic device integration, especially for flexible wearable device applications.

Surgical management and post-operative functional outcomes of patients with a penile fracture-a single centre experience over 10 years.

BACKGROUND: Penile fractures are uncommon urological emergencies which occur when there has been a breach in the tunica albuginea of the corpora cavernosum that may be unilateral and bilateral and can extend to involve the urethra. AIM: To assess the management and outcomes of penile fractures in a single institution in Ireland. METHODS: A retrospective review of the emergency theatre logbooks was performed between 2011 and 2021 to identify patients who had undergone an exploration for a suspected penile fracture. OUTCOMES: Seventeen patients were initially identified on review of theatre logbooks as having an exploration for a suspected penile fracture. Two patients were excluded from the study due to a lack of clinical notes being available. A further 4 patients on chart review were found to not have a penile fracture at exploration. RESULTS: Eleven patients had a confirmed penile fracture intra-operatively, four of whom had an associated urethral injury. Nine (9/11) patients had preserved normal erections post-operatively documented on follow-up; two, however, reported erectile dysfunction requiring phosphodiesterase inhibitors. CLINICAL IMPLICATIONS: Our study supports urgent surgical exploration for penile fractures to ensure good functional outcomes. STRENGTHS AND LIMITATIONS: This is a retrospective review of theatre logbooks to identify patients with a suspected penile fracture. CONCLUSION: The results of our cohort show a good outcome of erectile function following surgical repair of a penile fracture (9/11; 82%). Four patients (4/11; 36%) had a urethral injury diagnosed intra-operatively, one of whom required a formal urethroplasty.

Optical fiber-based sensor for in situ monitoring of cadmium sulfide thin-film growth.

This work presents a scheme for in situ monitoring of thin-film growth. A fiber-optic sensor based on Fabry-Perot interferometric technique has been established for the first time to monitor in situ growth of thin films. This was applied for determining thickness of cadmium sulfide (CdS) thin films during growth. The fabrication process of CdS film was carried out in 30 mM cadmium acetate and thioacetamide solution at 60°C temperature. The estimated thickness determined during the growth was verified by scanning electron microscopy. This study shows that in situ measurement of the thickness of thin films is feasible by this new technique, and a close match of the estimated thickness was achieved.

Cerebrovascular disease in COVID-19: a systematic review and meta-analysis.

Background: The association between COVID-19 and acute cerebrovascular disease (CVD) has not been explored extensively. New data has come to light which may change previous results. Methods: We queried the PubMed electronic database from its inception until February 2022 for studies evaluating the incidence of stroke in COVID-19 patients. Results of the analysis were pooled using a random-effects model and presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: 37 studies consisting of 294,249 patients were included in our analysis. Pooled results show that the incidence of acute CVD events in COVID-19 positive patients is 2.6% (95% CI: 2.0-3.3; P<0.001). Cardioembolic (OR=14.15, 95% CI: 11.01 to 18.19, P<0.00001) and cryptogenic (OR=2.87, 95% CI: 1.91 to 4.32, P<0.00001) etiologies were associated with COVID-19 positivity. Risk factors for CVD events in patients with COVID-19 were atrial fibrillation (OR=2.60, 95% CI: 1.15 to 5.87, P=0.02), coronary artery disease (OR=2.24, 95% CI: 1.38 to 3.61, P=0.0010), diabetes (OR=2.46, 95% CI: 1.36 to 4.44, P=0.003) and hypertension (OR=3.65, 95% CI: 1.69 to 7.90, P=0.005). Conclusion: COVID-19 infection is associated with an increased risk for acute CVD and is associated with cardioembolic and cryptogenic etiologies and the risk factors of atrial fibrillation, coronary artery disease, diabetes and hypertension in COVID-19 positive patients.

Chromatic dispersion measurements using a virtually referenced interferometer.

We present a technique for measuring the chromatic dispersion of short-length (<1 m) optical devices using unbalanced spectral interferometry and a virtual reference path. The technique combines the speed and ease of measurement of unbalanced spectral interferometry with the accuracy of balanced spectral interferometry. We demonstrate measurement accuracy for group delay and the dispersion-length product of ~10(-3) ps/m (<0.0001% relative error) and ~10(-5) ps/m (<0.5% relative error), respectively. Measurement precision is demonstrated to be ~10(-5) ps/m (<0.15% relative deviation). We validate the technique via measurement of well-known dispersion standards.