Investigating the role of tumour-to-skin proximity in predicting nodal metastasis in breast cancer.

BACKGROUND: Understanding the factors influencing nodal status in breast cancer is vital for axillary staging, therapy, and patient survival. The nodal stage remains a crucial factor in prognostication indices. This study investigates the relationship between tumour-to-skin distance (in T1-T3 tumours where the skin is not clinically involved) and the risk of nodal metastasis. METHODS: We retrospectively reviewed data from 100 patients who underwent neoadjuvant chemotherapy (NACT). Besides patient demographics and tumour variables, a radiologist retrospectively reviewed pre-operative MRI to measure tumour-to-skin distance. R core packages were used for univariate (χ2 and T-Wilcoxon tests) and bivariate logistic regression statistical analysis. RESULTS: Of 95 analysable datasets, patients' median age was 51 years (IQR: 42-61), 97% were symptomatic (rest screen detected), and the median tumour size was 43 mm (IQR, 26-52). On multivariate analysis, increasing invasive tumour size (p = 0.02), ER positivity (p = 0.007) and shorter tumour-to-skin distance (p = 0.05) correlated with nodal metastasis.  HER2 was not included in multivariate analysis as there was no association with nodal status on univariate analysis. In node-positive tumours, as tumour size increased, the tumour-to-skin distance decreased (r = - 0.34, p = 0.026). In node-negative tumours, there was no correlation (r = + 0.18, p = 0.23). CONCLUSION: This study shows that non-locally advanced cancers closer to the skin (and consequent proximity to subdermal lymphatics) are associated with a greater risk of nodal metastasis. Pre-operative identification of those more likely to be node positive may suggest the need for a second-look USS since a higher nodal stage may lead to a change in therapeutic strategies, such as upfront systemic therapy, node marking, and axillary clearance without the need to return to theatre following sentinel node biopsy.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

14†Surgical treatment of heavy eye syndrome by modified loop myopexy.

Heavy eye syndrome or convergent strabismus fixus is an acquired strabismus typically seen in eyes with high myopia. We present a case, discuss the aetiology and management, and include a short video illustrating the surgical procedure undertaken.A 47-year-old highly myopic woman with h/o bilateral cataract surgery and B/L scleral buckling for retinal detachments, had left esotropia and hypotropia measuring more than 40 prism dioptres base-out and 12 prism dioptres base up. MRI orbits showed bilateral asymmetrical medial deviation of ocular bulbs, more on left side. Also, there was degeneration of lateral rectus-superior rectus band with displacement of lateral rectus downwards.She underwent Botox to bi-medial recti after which she could demonstrate potential for binocular single vision. A left un-augmented loop Myopexy procedure and recession of the left medial rectus was thereafter performed under general anaesthesia. After surgery, her eyes were binocularly aligned for near with minimal esotropia for distance.This case suggests that patients with significant esotropia combined with high myopia should be suspected to have heavy eye syndrome. Orbital imaging should be undertaken to demonstrate the anatomical abnormality and muscle paths to confirm a definite diagnosis. Modified Loop Myopexy was found to be effective in this case of heavy eye syndrome.

Exploring the outer limits of polyplexes.

Histidine-containing polymers show promise in their transport of nucleic acids in vitro and in vivo. In addition to the pH-buffering histidine component, the polymer often contains a protonated component at physiological pH, such as lysine. These polyplexes usually accumulate in the tumor by enhanced permeability and retention, which has proved disappointing in clinical trials. We presently compare two histidine-lysine (HK) peptide polyplexes for their neuropilin-1-mediated transport of plasmids in vivo. While the polymerized HK (H2KC-48) polyplex was markedly better than the monomeric HK (H2K) polyplex in vitro, both HK polyplexes were effective in transfecting tumor xenografts over a wide range of peptide and plasmid ratios. Nevertheless, polyplexes of low peptide/DNA ratios gave higher tumor transfection and specificity than those of higher ratios. Surprisingly, there was minimal to no gel retardation of polyplexes made from these low ratios during electrophoresis. These results demonstrate that loosely packed HK polyplexes effectively transfected tumors in vivo.

'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.

Distribution and concentration pathway of particulate pollution during pandemic-induced lockdown in metropolitan cities in India.

To characterize the pollutant dispersal across major metropolitan cities in India, daily particulate matter (PM10 and PM2.5) data for the study areas were collected from the National Air Quality Monitoring stations database provided by the Central Pollution Control Board (CPCB) of India. The data were analysed for three temporal ranges, i.e. before the pandemic-induced lockdown, during the lockdown, and after the upliftment of lockdown restrictions. For the purpose, the time scale ranged from 1st April to 31st May for the years 2019 (pre), 2020, and 2021 (post). Statistical distributions (lognormal, Weibull, and Gamma), aerosol optical thickness, and back trajectories were assessed for all three time periods. Most cities followed the lognormal distribution for PM2.5 during the lockdown period except Mumbai and Hyderabad. For PM10, all the regions followed the lognormal distribution. Delhi and Kolkata observed a maximum decline in particulate pollution of 41% and 52% for PM2.5 and 49% and 53% for PM10, respectively. Air mass back trajectory suggests local transmission of air mass during the lockdown period, and an undeniable decline in aerosol optical thickness was observed from the MODIS sensor. It can be concluded that statistical distribution analysis coupled with pollution models can be a counterpart in studying the dispersal and developing pollution abatement policies for specific sites. Moreover, incorporating remote sensing in pollution study can enhance the knowledge about the origin and movement of air parcels and can be helpful in taking decisions beforehand.

Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy.

AIMS: This multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: Patients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. RESULTS: Among the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. CONCLUSION: Contemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Robust Quantum Memory in a Trapped-Ion Quantum Network Node.

We integrate a long-lived memory qubit into a mixed-species trapped-ion quantum network node. Ion-photon entanglement first generated with a network qubit in ^{88}Sr^{+} is transferred to ^{43}Ca^{+} with 0.977(7) fidelity, and mapped to a robust memory qubit. We then entangle the network qubit with a second photon, without affecting the memory qubit. We perform quantum state tomography to show that the fidelity of ion-photon entanglement decays ∼70 times slower on the memory qubit. Dynamical decoupling further extends the storage duration; we measure an ion-photon entanglement fidelity of 0.81(4) after 10 s.

Quantitative assessment of oil palm pollen after 23 years of cryobanking.

Cryopreservation of pollen grains is an effective means of conserving desired germplasm of crop plants. Cryoconserved pollen are expected to be long-lived and thus can be suitably retrieved to overcome hybridization constraints imposed by a variety of reasons. We ascertained the performance of oil palm pollen grains (Tenera hybrids) that were cryobanked 23 years ago using liquid nitrogen (-196 degree C). Cryostored pollen were assessed for viability, in-vitro germinability and vigour. Our analysis showed a marginal decline in viability, assessed through fluorochromatic reaction test, of cryopreserved pollen as compared to fresh ones (pre-storage assessment); however, the viability did not decline in the cryostate since it was last tested 15 years back. On the other hand, germinability and vigour of cryopreserved pollen were maintained to the levels of fresh pollen. Our study, for the first time, demonstrates the amenability of pollen grains for cryopreservation of any plant species beyond a period of two decades in general, and that for oil palm in particular. doi.org/10.54680/fr23110110512.

Optimization based ECG watermarking in RDWT-SVD domain.

With the increase in point of care services, communication of digital patient records through open network has multi-folded. This digital data is used to obtain the remote medical assistance from the smart healthcare centres. Protecting this data during transmission is a very big challenge. One of the most important medical data is electrocardiogram (ECG) signal which detects the cardiovascular diseases and any alteration in the signal may affect the diagnosis. In this work, an ECG watermarking based on redundant discrete wavelet transform (RDWT) and singular value decomposition (SVD) is developed. First, the ECG signal is converted into 2-D matrix using pan-tompkins algorithm. Then, we use the hybrid of RDWT and SVD to conceal the patient data and logo image into the 2-D ECG image. We also use hybrid of optimization scheme to improve the robustness of the watermark. Preliminary experimental results indicate the optimal invisibility and robustness result is more effective up to 97.89% than the traditional schemes respectively, which makes it suitable for ownership authentication of ECG signal.

Cryoconservation of in vitro grown shoot tips of Cicer microphyllum: A crop wild relative of chickpea.

BACKGROUND: Cicer microphyllum Benth. is a crop wild relative (CWR) of chickpea (C. arietinum L.), that possess useful genes for cold and drought tolerance. The species is being conserved in the In Vitro Active Genebank for short- to medium-term conservation. Cryopreservation would be a useful complementary approach for its long-term conservation. OBJECTIVE: The current work aimed to develop an efficient cryoconservation protocol for cryobanking of C. microphyllum shoot tips. MATERIALS AND METHODS: In vitro shoot tips excised from 4-month old shoot cultures grown on B5 + 0.5 mg/L KIN + 0.1 mg/L NAA + 10 mg/L AgNO3 medium were cryoconserved using a droplet-vitrification technique. Post-thaw regrowth was evaluated after: (i) preculture medium (B5 basal, B5 + 3, 4, 6 and 10% sucrose), (ii) preculture incubation temperature (25 ± 2, 10, 8 and 22/5 degree C), (iii) PVS2 duration (10, 20, 30. 40, 50 and 60 min) and (iv) regrowth medium (B5) supplemented with 0.5 mg/L KIN + 0.1 NAA mg/L; 0.5 mg/L KIN + 0.1 mg/L NAA + 10 mg/L AgNO3; 0.2 mg/L BAP + 10 mg/L AgNO3; 0.2 mg/L BAP + 20 mg/L AgNO3 and 0.2 mg/L BAP + 30 mg/L AgNO3. RESULTS: In vitro shoot tips grown on B5 + 0.5 mg/L KIN + 0.1 mg/L NAA + 10 mg/L AgNO3, precultured on B5 + 6% sucrose at 10 degree C for 3 days, followed by PVS2 treatment for 20 min, unloading solution for 60 min and regrowth on B5 + 0.2 mg/L BAP + 20 mg/L AgNO3 resulted in highest survival (57%) and regrowth (40%) after cryoconservation. CONCLUSION: The standardized protocol was successfully used for cryobanking of in vitro shoot tips of C. microphyllum in the In Vitro Base Genebank of ICAR-NBPGR, New Delhi. Doi.org/10.54680/fr23610110412.

When to stop? Mammographic surveillance in breast cancer survivors aged 70 years and older.

AIM: To assess the rates of breast cancer detected in postoperative surveillance mammograms in women >70 Years and overall mortality in this age group. MATERIALS AND METHODS: Four hundred and ninety-eight patients were identified retrospectively from a database from a single large UK hospital. Patients were included in the study if they were female, aged >70 years at diagnosis of either invasive breast cancer or ductal carcinoma in situ (DCIS), had surgical treatment between 1 January 2010 and 31 December 2014, and no previous diagnosis of breast cancer. Statistical analysis was performed using Excel, using the X2 test, with p ≤ 0.05 considered statistically significant. RESULTS: The mean age of women included in this study was 77 years. The mean number of postoperative surveillance mammograms performed per patient was 4.2. In the 5-year follow-up, there was a local recurrence rate of 1.9% (n=6) and a contralateral breast cancer rate of 1% (n=6). The 5-year overall mortality rate was 17.7% (n=88), and the 5-year breast cancer-specific mortality rate was 7.2% (n=36). CONCLUSION: This study demonstrated low local recurrence and contralateral breast cancer rates during the 5-year follow-up period. Clear discussions therefore need to be held with older patients about the value of postoperative mammographic surveillance. Further research is required regarding patient opinion and experience to help develop more consistent guidelines.

Ultrasound-positive axillary lymph nodes in early breast cancer: can a patient subgroup avoid axillary lymph node dissection? A simple algorithm is suggested.

INTRODUCTION: National UK guidelines suggest that axillary lymph node dissection (ALND) is no longer mandatory for selected early node-positive breast cancer patients. Our study aimed to identify patients with early breast cancer and ultrasound (USS)-positive axillary metastasis who possess low burden of axillary disease and can avoid ALND. METHODS: We conducted a 5-year study of prospectively collected data of patients with clinically T1-2, N0 breast cancer and a positive USS-guided axillary biopsy. Primary outcome was involvement of 1-2 lymph nodes (low disease burden) or ≥3 lymph nodes (higher axillary disease) on final ALND histology. Tumour type, size, grade, multifocality, receptor status, number of abnormal imaged nodes and presence of lympho-vascular invasion (LVI) were recorded. Data were analysed using chi-squared and Student's t-test. RESULTS: One hundred and sixty-six patients underwent ALND for pT1-2 breast cancer. Seventy patients had no clinically palpable lymphadenopathy but a positive USS-guided biopsy. Of 70 patients, 32 women (46%) had low disease burden, whereas 38 women (54%) had higher axillary disease in final histology. LVI and >1 abnormal lymph node on USS were both significantly associated with higher disease burden (p = 0.050 and 0.009, respectively). CONCLUSION: Our study confirms the presence of an important patient cohort, who are clinically node-negative with a positive USS-guided biopsy and a low volume of axillary disease. No imaging modality currently has the accuracy required to identify patients with this low disease burden preoperatively but we propose a simple algorithm for axillary management in this subgroup.

Emergence of a compositional neural code for written words: Recycling of a convolutional neural network for reading.

The visual word form area (VWFA) is a region of human inferotemporal cortex that emerges at a fixed location in the occipitotemporal cortex during reading acquisition and systematically responds to written words in literate individuals. According to the neuronal recycling hypothesis, this region arises through the repurposing, for letter recognition, of a subpart of the ventral visual pathway initially involved in face and object recognition. Furthermore, according to the biased connectivity hypothesis, its reproducible localization is due to preexisting connections from this subregion to areas involved in spoken-language processing. Here, we evaluate those hypotheses in an explicit computational model. We trained a deep convolutional neural network of the ventral visual pathway, first to categorize pictures and then to recognize written words invariantly for case, font, and size. We show that the model can account for many properties of the VWFA, particularly when a subset of units possesses a biased connectivity to word output units. The network develops a sparse, invariant representation of written words, based on a restricted set of reading-selective units. Their activation mimics several properties of the VWFA, and their lesioning causes a reading-specific deficit. The model predicts that, in literate brains, written words are encoded by a compositional neural code with neurons tuned either to individual letters and their ordinal position relative to word start or word ending or to pairs of letters (bigrams).

Impact of coronavirus disease 2019 on ENT clinical practice and training: the resident's perspective.

BACKGROUND: The arrival of the coronavirus disease 2019 pandemic disrupted life suddenly and forcefully, and healthcare systems around the world are still struggling to come to terms with it. This paper reviews the impact of the pandemic on ENT practice and training. METHODS: The present manuscript was developed as a narrative review to examine the role of otorhinolaryngologists in the management of the pandemic, and assess its impact on practice and training in the specialty. RESULTS: Otorhinolaryngologists handle secretions of organs implicated in disease transmission, leaving them particularly vulnerable even while performing simple procedures. Although the pandemic increased skill expectations, it simultaneously reduced learning opportunities for trainees. In addition, attention to emergencies has been delayed. Further, the suspension of elective procedures has affected patients with malignancies. CONCLUSION: While planning service resumption, provisions need to be made for protective equipment and training; improving teleconsultation services will help provide sustainable care during further waves.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.