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Introduction: Glutamate excitotoxicity is causal in striatal neurodegeneration underlying motor dysfunction and cognitive deficits in Huntington's disease (HD). Excitatory amino acid transporter 2 (EAAT2), the predominant glutamate transporter accounting for >90% of glutamate transport, plays a key role in preventing excitotoxicity by clearing excess glutamate from the intrasynaptic cleft. Accordingly, EAAT2 has emerged as a promising therapeutic target for prevention of neuronal excitotoxicity underlying HD and other neurodegenerative diseases., Methods: We have previously designed novel EAAT2 positive allosteric modulator GT951, GTS467, and GTS551, with low nanomolar efficacy in glutamate uptake and favorable pharmacokinetic properties. In this study, we test the neuroprotective abilities of these novel EAAT2 activators in vivo using the robust Drosophila HD transgenic model expressing human huntingtin gene with expanded repeats (Htt128Q)., Results: All three compounds significantly restored motor function impaired under HD pathology over a wide dose range. Additionally, treatment with all three compounds significantly improved HD-associated olfactory associative learning and short-term memory defects, while GT951 and GTS551 also improved middle-term memory in low-performing group. Similarly, treatment with GT951 and GTS551 partially protected against early mortality observed in our HD model. Further, treatment with all three EAAT2 activators induced epigenetic expression of EAAT2 Drosophila homolog and several cognition-associated genes., Conclusion: Together, these results highlight the efficacy of GT951, GTS467 and GTS551 in treating motor and cognitive impairments under HD pathology and support their development for treatment of HD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhatnagar, Parmar, Barbieri, Bearoff, Elefant and Kortagere.)

Objective: Body tissue composition plays a crucial role in the multisystemic processes of advanced liver disease and has been shown to be influenced by transjugular intrahepatic portosystemic shunt (TIPS). A differentiated analysis of the various tissue compartments has not been performed until now. The purpose of this study was to evaluate the value of imaging biomarkers derived from automated body composition analysis (BCA) to predict clinical and functional outcome., Methods: A retrospective analysis of 56 patients undergoing TIPS procedure between 2013 and 2021 was performed. BCA on the base of pre-interventional CT examination was used to determine quantitative data as well as ratios of bone, muscle and fat masses. Furthermore, a BCA-derived sarcopenia marker was investigated. Regarding potential correlations between BCA imaging biomarkers and the occurrence of hepatic encephalopathy (HE) as well as 1-year survival, an exploratory analysis was conducted., Results: No BCA imaging biomarker was associated with the occurrence of HE after TIPS placement. However, there were significant differences in alive and deceased patients regarding the BCA-derived sarcopenia marker (alive: 1.60, deceased: 1.83, p = 0.046), ratios of intra- and intermuscular fat/skeletal volume (alive: 0.53, deceased: 0.31, p = 0.015) and intra- and intermuscular fat/muscle volume (alive: 0.21, deceased: 0.14, p = 0.031)., Conclusion: A lower amount of intra- and intermuscular adipose tissue might have protective effects regarding liver derived complications and survival., Advances in Knowledge: Precise characterization of body tissue components with automated BCA might provide prognostic information in patients with advanced liver disease undergoing TIPS procedure., Competing Interests: FundingOpen Access funding enabled and organized by Projekt DEAL.

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone., (© 2023. The Author(s).)

Objective: The purpose of this study was to report quality of life of newly diagnosed breast cancer patients from India in a large cohort using the EQ-5D-5L instrument., Methods: The study used longitudinal data of 500 breast cancer and 200 non-cancer subjects registered at our centre, during June 2019 and March 2022. The EQ-5D-5L and EQ-VAS instruments were used to measure and compare utility scores among cancer and non-cancer subjects. Descriptive statistics were analyzed and Tobit regression model were used to confirm the predictors of the utility score., Results: The cancer subjects had a mean EQ-ED-5L utility score of 0.8703 (SD=0.121), 0.8745 (SD=0.094) and 0.8902 (SD=0.107) at the time of baseline, completion and follow up surveys respectively.  EQ-5D-5L values had significantly worsened after diagnosis of cancer as compared to the non-cancer cohort (0.87 vs. 0.93, p value 0.000). EQ-5D-5L utility scores as per stage for the cancer cohort were 0.88, 0.86 and 0.83 respectively for stage I-II, III and IV. Similarly, the EQ-VAS scores for stage I-II, III and IV were 74.9, 72.6 and 73.2 respectively. Multivariate analysis confirmed strong association of age, religion and income with the utility-values., Conclusion: This is the first longitudinal study reporting the utility scores derived from a large cohort of breast cancer patients demonstrating lower utility scores compared to non-cancer cohort. The utility scores also improve post treatment completion for cancer patients and decrease with higher stage at diagnosis. This information will be useful for future health economic research in India pertaining to breast cancer.

Background: Thoracolumbar burst fractures include a spectrum of treatment options ranging from conservative management to multilevel fusion with or without corpectomy. Given the variability of treatment options, consideration of radiographic outcomes with different treatment modalities should be a critical consideration in management., Methods: A retrospective review was conducted evaluating all patients presenting with spine fractures over a 7-year period. Inclusion criteria were limited to adults with acute, traumatic burst fractures of the thoracolumbar joint levels T11-L2. Patients were categorized by nonoperative management, short-segment fusion, multilevel fusion without anterior column reconstruction, and corpectomy. Radiographic information collected included kyphotic angle (KA), Cobb angle (CA), and Gardner angle (GA)., Results: In total, 117 patients (70.5%) were successfully treated nonoperatively, 4 (2.4%) underwent short-segment fusion, 28 (16.9%) underwent multilevel fusion, and 12 (7.2%) underwent corpectomy. All nonoperative patients demonstrated significantly worse kyphosis at 1-year follow-up as measured by KA, CA, and GA ( P < 0.001). Patients undergoing corpectomy had the largest improvement in kyphosis with an average improvement of 14.1° on KA, 8.1° on CA, and 11.0° on GA ( P < 0.001, P = 0.098 , and P = 0.004, respectively). In comparison, patients undergoing multilevel fusion showed an average improvement of 2.6°, 2.7°, and 3.3° of correction on GA, CA, and KA, respectively ( P > 0.05)., Conclusions: Nonoperative and short-segment fusion burst fracture patients demonstrated significantly worse kyphosis at 1-year follow-up. Patients undergoing corpectomy demonstrated a superior improvement in kyphotic correction compared with those undergoing multilevel fusion and short-segment fusion., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Probiotics are co-prescribed with co-amoxiclav to prevent antibiotic-associated diarrhea (AAD). The study assesses the co-prescription pattern of probiotics with co-amoxiclav in pediatric patients with respiratory tract infections (RTIs)., Methods: This was a mixed methods research study with a retrospective study and a prospective survey. The retrospective part included a multicenter, observational, real-world study utilizing patients' electronic medical records for three years (2018-2020) from seven outpatient pediatric clinics and hospitals. The qualitative evaluation was performed with a predefined questionnaire., Results: The patients having RTIs (N=984) were prescribed Clamp ® (46.7%), CAA (23.8%), and CAM (29.5%). The mean age of the patients was 4.05 years, with 59.25% males and most patients having upper RTIs. Co-amoxiclav was prescribed twice daily for one to 15 days. A significantly lesser number of probiotic co-prescriptions were observed with Clamp ® (19.57%) than with CAA (38.46%) and CAM (29.31%) at baseline ( p <0.001). Similar findings were observed for follow-up visits one and two. Saccharomyces boulardii , Bacillus clausii ,and lactic acid bacillus were the most commonly co-prescribed probiotics. The qualitative evaluation indicated that most clinicians were aware of the co-amoxiclav-related gastrointestinal side effects and the benefits of probiotics in preventing them., Conclusion: The frequency of co-prescriptions of probiotics with Clamp ® among pediatric patients with RTIs was significantly less, potentially indicating better gastrointestinal tolerability., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Choudhury et al.)

Nita S. Nair Background  Radiotherapy (RT) is an important modality in the management of breast cancers (BC). Large randomized trials have suggested that prophylactic regional nodal irradiation inclusive of internal mammary lymph nodes (IMLN) reduces BC-related mortality. However, the adoption of IMLN-RT has been variable due to relative benefits and toxicity concerns. Methods  A survey was emailed to radiation oncologists (ROs) across the country wherein they were asked about their practice regarding IMLN-RT in BC. Results  We received 128 responses, which included radiation oncologists across both private institutions (PIs) and government institutions (GIs). Fifty-six (43.8%) routinely offer prophylactic(p) IMLN-RT and an additional 15 (11.71%) suggested they would have offered it in the absence of logistic constraints. Almost all, 121 (94.5%) radiate the IMLN in case of radiologically positive lymph nodes (LNs). Fifty-six ROs (43.8%) offered prophylactic IMLN-RT in node-negative disease. Among those who did not offer IMLN-RT, most (84.72%) felt the clinical evidence was equivocal. Of the 56 who offered pIMLN-RT, 34/56 (60.71%) offered to locally advanced tumors, 20/56 (35.71%) offered to all inner and central tumors (ICQT), 29/56 (51.78%) to > 4 axillary LN-positive and 9/56 (16.07%) to any axillary LN-positive. The majority, i.e., 36/56 (64.28%) radiated upper three intercostal spaces, 9 (16.07%) radiated upper five intercostal spaces, and 6 (10.9%) decided based on tumor location, while 5 (9%) irradiated one space below the involved space. Overall, simulation-based planning was undertaken in 99% of PIs as opposed to 89% of GIs ( p  = 0.03). The majority of ROs, i.e., 92 (72.4%) preferred IMRT to IMLN-RT. In addition, the surgical approach to IMLN was practiced by surgeons at 18 (14%) centers, of which 13 (72.22%) operated the IMLN when radiologically evident. The IMLN dissection was preferentially performed for second and third intercostal spaces as suggested in 10 (55.55%) responses, while 8 (44.44%) performed thoracoscopic dissection of the IMLN chain. The distribution of prophylactic, definitive IMLN-RT, and IMLN dissection did not differ significantly between GI and PI ( p  = NS). Conclusion  pIMLN-RT is still not the standard protocol in most centers citing equivocal evidence in the literature. Logistics, though different in GIs and PIs, did not impact the decision of pIMLN-RT. Further efforts would be required to standardize practice in IMLN across India., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction: An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level., Methods: Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score., Results: The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized., Conclusion: A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Purpose: To assess the radiological morphometric parameters of OLIF surgical technique in lower lumbar spine among normal and in patients with adult degenerative spine (levoscoliosis and dextroscoliosis)., Method: Standing AP radiographs and MRI in supine position were taken. Patients were divided into 3 groups based on Cobbs' angle into normal, levo and dextro scoliosis. Moros classification was used to calculate bare window (BW), vascular window (VW), Psoas window (PW), psoas major height (pmh) and width (pmw) at lower lumbar levels and measurements were done on PACS., Results: Seventy five patients (25 in each group) were assessed. BW has trend from L2-L3 > L3-L4 > L4-L5 in dextro and levoscoliosis. PW has trend from L3-L4 > L2-L3 > L4-L5 in levoscoliosis and normal group. VW has trend from L4-L5 > L3-L4 > L2-L3 in dextro and levoscoliosis; pmw has trend from L4-L5 > L3-L4 > L2-L3 in Levo and dextroscoliosis; pmh has trend from L4-L5 > L3-L4 > L2-L3 in levoscoliosis and normal group., Conclusion: BW was noted to be highest at L3-4, lowest at L4-5 in normal group. VW was constant, BW showed a reverse trend with PW across all the levels. Though levoscoliosis group of patients had significantly higher BW, psoas retraction issues are to be kept in mind in view of anatomically taught psoas., (© 2022. The Author(s), under exclusive licence to Scoliosis Research Society.)

Purpose: This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer., Methods: From April 2019 to 2020, 60 patients with stage II-III invasive breast cancer planned for adjuvant taxane-based chemotherapy and radiotherapy (RT) were accrued. Local ± regional (excluding the internal mammary nodal region) RT (40 Gy in 15 fractions ± boost) was started with the third cycle of an adjuvant taxane in a 3-weekly schedule or with the eighth cycle in a weekly schedule., Results: Thirty-six patients received 3-weekly paclitaxel regimen and 24 received weekly paclitaxel regimen. The commonly used technique was three-dimensional conformal RT which was employed in 58% of patients. Regional RT, including the medial supraclavicular region, was done in 42 patients (70%). No dose-limiting (grade 3 or 4) toxicity was documented and all patients completed CTRT without any treatment interruption. The median ejection fraction pre and post CTRT 6 months was 60% ( p = 0.177). The median value of cardiac enzyme (Troponin T ng/L) decreased from 37 to 20 ( p = 0.009) post CTRT 6 months. Of the 54 patients who underwent the pulmonary function tests, there was no significant difference in various parameters like functional vital capacity (FVC) (2.29 versus 2.2 L, p = 0.375), forced expiratory volume at 1 second (FEV1) (1.86; 1.82; p = 0.365), FEV1/FVC (81.5; 81.43; p = 0.9) and diffusion lung capacity for carbon monoxide (88.3; 87.6; p = 0.62). At a median follow-up of 34 months, the 3-year actuarial rate of disease-free survival and overall survival was 75% and 98.3%, respectively. Quality of life scores (QOL) improved after treatment for most of the domains comparable to the pre-RT scores., Conclusion: Taxane-based adjuvant CTRT is a safe option and results in minimal toxicity and excellent compliance. It has favourable impact on cardio-pulmonary profile and QOL scores., Competing Interests: The authors declare no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Green innovation is an essential and burning topic for environmental and organizational performance. Therefore, this research aims to examine the effect of green innovation on environmental performance, which leads to organizational performance. Another objective is to measure the impact of two dimensions of green innovation, such as green process & green product measures, on green innovation. The second prime aim of this research is to evaluate the moderation of management commitment & human resource practices in an association between green innovation and organizational & environmental performance. A total of 320 employees provided their perspectives on a self-administrated questionnaire from the textile industry of Pakistan. We have employed SEM-based multivariate modeling to examine the data. This research has measured the reflective indicators measurement model through confirmatory factor analysis, an obvious choice of structural equation modeling to examine observed and unobserved variables and indicators using PLS-SEM (partial least square-structural equation modeling). The research findings reveal a positive & significant effect of product & process innovation on green innovation. Further, green innovation significantly impacts environmental and organizational performance. A two-way interaction (moderation) of human resource practices & green innovation does not have a cogent moderating effect on organizational & environmental performance. However, management commitment has a significant moderation between green innovation & organizational performance. A three-way interaction (moderated moderation) model finds a substantial effect on organizational attainment but an insignificant impact on environmental performance. The research outcomes significantly contribute and suggest that practitioners and policymakers must institutionalize green innovation practices in their organizations to enhance their organizational and environmental performance. HR practitioners play a vibrant role in creating green norms and organizational culture. The study findings also suggest that management commitment to green innovation advocates organization-level transformations toward adopting green practices., (© 2023 The Authors. Published by Elsevier Ltd.)

People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and β-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery., (© 2022. The Author(s).)

Background: Asymptomatic COVID-19 subjects can transmit the infection for as many as 14 days and are regarded as a significant factor in the rapid spread of the COVID-19 pandemic. This exploratory study aimed to determine any additional benefits of selected homeopathic medicines compared with placebo in asymptomatic COVID-19 individuals receiving standard care., Methods: This open-label, randomized, placebo-controlled, exploratory trial was undertaken at a COVID Care Centre (CCC) in Madhya Pradesh, India. Patients ( n  = 200, 18-65 years, both sexes) having a positive RT-PCR and asymptomatic during admission were enrolled. They were randomly assigned to one of four groups (each n  = 50): Arsenicum album 30C ( Ars. alb. ), Camphora 1M ( Camph .), Bryonia alba 30C (Bry. alb.) and placebo ( Pl .). All the patients were given standard care. The primary outcome was the number of patients becoming RT-PCR negative for SARS-CoV-2 at days 5, 10 and 15., Results: In total, 200 asymptomatic COVID-19 patients were enrolled. One hundred and seventy-seven patients became RT-PCR negative by day 15; 88%, 80%, 98% and 88% from Ars. alb., Camph., Bry. alb. and Pl. respectively. A Chi-square test of association for the total patients who became RT-PCR negative for SARS-Cov-2 in each group showed a marginal statistical significance (Chi-square: 8.1, p  = 0.04). A two-proportion Z -test comparing each pre-identified homeopathic medicine with placebo showed marginal statistical significance ( p  = 0.05) for Bry alb. only. Median time in days to RT-PCR negative (Kaplan Meier analysis) was 10 days in each of the groups., Conclusion: There was some evidence that, compared with Ars alb., Camph . or Pl. , Bry. alb. was associated with an increased number of patients who became RT-PCR negative for COVID-19 by day 15. The possible effect exerted needs to be investigated in additional research., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Thrombotic thrombocytopenic purpura (TTP) is caused by the deficiency of ADAMTS13, a von Willebrand factor cleaving protease, which results in thrombotic microangiopathy. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis leading to organ damage. It has an extremely high mortality rate if left untreated, making early diagnosis and treatment of the utmost importance. We report a case of TTP that developed after vaccination with Ad26.COV2.S COVID vaccine. We present a case of a 50-year-old African American female who presented with dyspnea one week after receiving the first dose of Ad26.COV2.S vaccine. Initial labs showed anemia, thrombocytopenia, and markers of intravascular hemolysis. The suspicion for thrombotic thrombocytopenic syndromes (TTS), vaccine-induced thrombotic thrombocytopenia (VITT), TTP, and Immune thrombocytopenic purpura (ITP) was high based on the history and laboratory results. Computed tomography (CT) of the chest and ultrasound of bilateral lower extremities did not show any evidence of thrombosis. The absence of thrombosis in the presence of a high PLASMIC score increased the suspicion of TTP over the other differentials. Diagnosis of TTP was confirmed when the ADAMTS13 level was low with an elevated autoantibody inhibitor level. The patient underwent treatment with corticosteroids, plasmapheresis, and rituximab with improvement in symptoms and platelet count. TTP and VITT are the possible differential diagnosis for a patient presenting with anemia, thrombocytopenia, and signs of hemolysis after vaccination with Ad26.COV2.S. It is necessary to differentiate these two clinical entities as the management varies based on the diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ramanan et al.)

Background The high prevalence of pneumonia and renal involvement in coronavirus disease 2019 (COVID-19) leads to frequent acid-base abnormalities in serious patients and affects prognosis. In this study, we aimed to assess the arterial blood gas (ABG) and acid-base patterns in COVID-19 patients admitted to a tertiary care hospital. Methodology A retrospective observational study was conducted in a designated COVID-19 hospital involving 267 reverse transcription-polymerasechain reaction-positive COVID-19 patients. Demographic and laboratory data including ABG data within the first day after admission and in patients with multiple ABG analyses, only the first measurement was collected and analyzed statistically, including its association with comorbidities. Results The most common age group of the patients was 51-60 years (30.8%), with a male predominance (male:female = 2.7:1). The most common comorbidities were hypertension, diabetes mellitus, and chronic obstructive pulmonary disease found in 147 (55%) COVID-19 patients. Alkalosis and acidosis were observed in 145 (54.3%) and 50 (18.7%) patients, respectively. The most common ABG abnormality observed was primary respiratory alkalosis with secondary metabolic acidosis in 67 (25.1%) patients, followed by primary respiratory alkalosis with secondary metabolic alkalosis in 54 (20.2%) patients. Statistically significant negative correlation was found with PaCO 2 and pH (r = -0.530, p < 0.0001), statistically significant positive correlation was found between pH and base (r = 0.533, p < 0.0001), pH and TCO 2 (r = 0.260, p < 0.0001), and pH and HCO 3 (r = 0.354, p < 0.0001). Conclusions Acid-base abnormalities are commonly encountered in COVID-19 patients. Respiratory alkalosis as a part of a single or mixed pattern on ABG was the most common pattern found in critically ill COVID-19 patients. ABG on admission in moderate-to-severe COVID-19 patients can help in the early correction of metabolic abnormalities leading to improved patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sanghani et al.)

Background: In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients., Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH., Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6-60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2-11.6) usage of HER2-targeted therapy in the 2008 cohort., Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment., Competing Interests: None

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment., Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity., Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients., Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer., Competing Interests: None

Disruption of histone acetylation-mediated gene control is a critical step in Alzheimer's Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin (ChIP-seq) and transcriptional (RNA-seq) profiling study in Drosophila melanogaster brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2 D. melanogaster neural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor binding sites close or within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in coenzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.

Background: Triple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide., Methods: We analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables., Results: There were 1297 patients with median age of 38 years; 41 (33.3%) among 123 tested were BRCA-positives. Among these 593 (45.7%) had stage III disease, 1279 (98.6%) were grade III, 165 (13.0%) had peri-nodal extension (PNE), 212 (16.0%) lympho-vascular invasion (LVI), and 21 (1.6%) were metaplastic; 1256 (96.8%) received chemotherapy including 820 (63.2%) neoadjuvant with 306 (40.0%) pCR. Grade ≥3 toxicities occurred in 155 (12.4%) including two deaths and 3 s-primaries. 1234 (95.2%) underwent surgery [722 (55.7%) breast conservations] and 1034 (79.7%) received radiotherapy. At a median follow-up of 54 months, median disease-free (DFS) was 92.2 months and overall survival (OS) was not reached. 5-year estimated DFS and OS was 65.9% and 80.3%. There were 259 (20.0%) failures; predominantly distant (204, 15.7%) - lung (51%), liver (31.8%). In multivariate analysis presence of LVI (HR-2.00, p-0.003), PNE (HR-2.09 p-0.003), older age (HR-1.03, p-0.002) and stage III disease (HR-4.89, p-0.027), were associated with poor OS., Conclusion: Relatively large contemporary data of non-metastatic TNBC confirms aggressive biology and predominant advanced stage presentation which adversely affects outcomes. The data strongly indicate the unmet need for early detection to optimize care., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Gorham-Stout disease (GSD), a fibro-lymphovascular entity in which tissue replaces the bone leading to massive osteolysis and its sequelae, rarely leads to spinal deformity/instability and neurological deficits. Here, we report a 12-year-old female who was diagnosed and treated for GSD., Case Description: A 12-year-old female presented with back pain, and the inability to walk, sit, or stand attributed to three MR/CT documented L2-L4 lumbar vertebral collapses. Closed biopsies were negative. However, an open biopsy diagnosed GSD. She underwent a dorsal-lumbar-to-pelvis fusion (i.e., T5-T12 through L5/S1/S2) using multilevel pedicle screw/rod stabilization and human leukocyte antigens (HLAs) matched allograft (i.e. from her father). Postoperatively, she was treated with "off-label" teriparatide injections, bisphosphonates, and sirolimus. Four years later, while continuing the bisphosphonate therapy, she remained stable., Conclusion: Surgical multirod stabilization from T5 to S2, supplemented with HLA compatible allograft, and multiple medical "off-label" therapies (i.e., teriparatide, sirolimus, and bisphosphonates) led to a good 4-year outcome in a 12-year-old female with GSD., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Localized necrotizing granulomatous lymphadenitis (GLA) is a very rare presentation of herpes simplex virus (HSV) infection. We are reporting a case that required multidisciplinary expertise to confirm the diagnosis and effectively treat the patient. Our patient had a recent diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and presented with hematuria and palpable inguinal lymph nodes. Affirmative diagnosis required a core biopsy of the lymph node with immunochemistry staining and polymerase chain reaction (PCR) testing. This case reviews the unusual presentation of an HSV infection and emphasizes the importance of maintaining a high index of suspicion for infection when treating an immunocompromised patient with persistent symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Parmar et al.)

The focus of this paper is to develop a comprehensive conceptual framework for the relationship between internal employer brand image and talent retention. An extensive and semi-systematic literature review identified a number of antecedents and consequences that have been empirically tested in various cutting-edge research studies that were conducted around the world. The existing literature is reviewed using a topical approach, and 66 research studies, most recent from various repositories, were carefully chosen and reviewed based on the criteria. Such studies have been discerned and synthesized in order to establish a complete and accurate understanding of the phenomenon. Finally, a comprehensive and relatively rich conceptual framework has been proposed for future empirical explanations in various social settings via prospective research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahmed, Azam, Qureshi, Hashem E, Parmar and Md Salleh.)

Frequent indoor tanning bed use is an established public health concern, yet research on tanning cessation interventions for frequent tanners is lacking. We describe the protocol for a brief, web-based tanning behavior change intervention and present evidence that it is acceptable and engaging to frequent indoor tanners. Lower tanning rates were not observed among participants receiving the intervention in a randomized controlled trial but participants' interest in changing tanning increased. This intervention could be a useful approach to increasing frequent tanners' interest in behavior change and openness to engaging within a more intensive, multi-component tanning cessation program. Trial Registration: NCT03448224 Clinical Trials.gov (https://clinicaltrials.gov/ct2/show/NCT03448224?cond=NCT03448224&draw=2&rank=1).

Red mud is a solid hazardous alumina industrial waste, which is rich in iron, titanium, aluminum, silicon, calcium, etc. The red mud contains 30-60% of hematite, which is suitable for shielding high energy X- and gamma rays. So, the iron rich red mud was converted into diagnostic X-ray shielding tiles through ceramic route by adding a certain weight percentage of BaSO 4 and binders (kaolin clay or sodium hexametaphosphate) with it. The kaolin clay tile possess sufficient impact strength (failure point is 852 mm for 19 mm steel ball) and flexural strength of ~25 N/mm 2 , which is suitable for wall applications. The 10.3 mm and 14.7 mm thick red mud:BaSO 4 :kaolin clay tile possess the attenuation equivalent to 2 mm and 2.3 mm lead at 125 kVp and 140 kVp, respectively. No heavy elements were found to leach out except chromium and arsenic from the sintered tiles. However, the leaching of Cr (0.6 ppm) and As (0.015 ppm) was found to be well below the permissible limit. These tiles can be used in the X-ray diagnosis, CT scanner, bone densitometry, and cath labs instead of toxic lead sheet and thereby to protect the operating personnel, public, and environment from radiation hazards., (Copyright © 2021 Elsevier B.V. All rights reserved.)

With recent advances in the field of artificial intelligence (AI) such as binarized neural networks (BNNs), a wide variety of vision applications with energy-optimized implementations have become possible at the edge. Such networks have the first layer implemented with high precision, which poses a challenge in deploying a uniform hardware mapping for the network implementation. Stochastic computing can allow conversion of such high-precision computations to a sequence of binarized operations while maintaining equivalent accuracy. In this work, we propose a fully binarized hardware-friendly computation engine based on stochastic computing as a proof of concept for vision applications involving multi-channel inputs. Stochastic sampling is performed by sampling from a non-uniform (normal) distribution based on analog hardware sources. We first validate the benefits of the proposed pipeline on the CIFAR-10 dataset. To further demonstrate its application for real-world scenarios, we present a case-study of microscopy image diagnostics for pathogen detection. We then evaluate benefits of implementing such a pipeline using OxRAM-based circuits for stochastic sampling as well as in-memory computing-based binarized multiplication. The proposed implementation is about 1,000 times more energy efficient compared to conventional floating-precision-based digital implementations, with memory savings of a factor of 45., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Parmar, Penkovsky, Querlioz and Suri.)

Objective: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use., Methods: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma., Results: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT., Conclusion: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.

Background: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying., Methods: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed., Results: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients., Conclusion: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus., Competing Interests: Declaration of competing interest There are no conflicts of interest relevant to this material for any of the authors., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer., Materials and Methods: Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform., Results: One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.7%). ESR1 , TP53 , and PIK3CA mutations account for 93% of all variants detected and predict poor overall survival in MBC (hazard ratio = 3.461; 95% CI, 1.866 to 6.42; P = .001). Patients with MBC had higher plasma cell-free DNA levels, higher variant allele frequencies, and more polyclonal variants, notably in ESR1 than in all other groups. Only 15 individuals had evidence of potential clonal hematopoiesis of indeterminate potential mutations., Conclusion: We were able detect ctDNA across the breast cancer spectrum, notably in MBC where variants in ESR1 , TP53 , and PIK3CA predicted poor overall survival. The assay could be used to monitor emergence of resistance mutations such as in ESR1 that herald resistance to aromatase inhibitors to tailor adjuvant therapies. However, we suggest caution is needed when interpreting results from a single plasma sample as variants were also detected in a small proportion of HCs., Competing Interests: Daniel Fernandez-Garcia Employment: Almirall (I) Stock and Other Ownership Interests: Exonate Ltd (I) Travel, Accommodations, Expenses: Almirall (I) Carlo Palmieri Honoraria: Pfizer Consulting or Advisory Role: Pfizer, Daiichi-Sankyo, Lilly, Novartis, Seattle Genetics Research Funding: Pfizer, Daiichi-Sankyo Travel, Accommodations, Expenses: Roche Simak Ali Stock and Other Ownership Interests: Carrick Therapeutics Research Funding: Carrick Therapeutics, AstraZeneca Patents, Royalties, Other Intellectual Property: Royalty from Carrick Therapeutics Uncompensated Relationships: Carrick Therapeutics Justin Stebbing Leadership: BB Healthcare Trust, Xerion Healthcare, Springer Nature Consulting or Advisory Role: Vaccitech, Celltrion, TLC Biopharmaceuticals, Vor Biopharma, Lansdowne, Vitruvian, Singapore Biotech, Benevolent AI R. Charles Coombes Research Funding: DNAe, Pfizer, AstraZeneca Patents, Royalties, Other Intellectual Property: I have shares in Carrick ltd and I am also a patent holder in the drug CT7001 that Imperial College has licensed to them No other potential conflicts of interest were reported. Daniel Fernandez-Garcia Employment: Almirall (I) Stock and Other Ownership Interests: Exonate Ltd (I) Travel, Accommodations, Expenses: Almirall (I) Carlo Palmieri Honoraria: Pfizer Consulting or Advisory Role: Pfizer, Daiichi-Sankyo, Lilly, Novartis, Seattle Genetics Research Funding: Pfizer, Daiichi-Sankyo Travel, Accommodations, Expenses: Roche Simak Ali Stock and Other Ownership Interests: Carrick Therapeutics Research Funding: Carrick Therapeutics, AstraZeneca Patents, Royalties, Other Intellectual Property: Royalty from Carrick Therapeutics Uncompensated Relationships: Carrick Therapeutics Justin Stebbing Leadership: BB Healthcare Trust, Xerion Healthcare, Springer Nature Consulting or Advisory Role: Vaccitech, Celltrion, TLC Biopharmaceuticals, Vor Biopharma, Lansdowne, Vitruvian, Singapore Biotech, Benevolent AI R. Charles Coombes Research Funding: DNAe, Pfizer, AstraZeneca Patents, Royalties, Other Intellectual Property: I have shares in Carrick ltd and I am also a patent holder in the drug CT7001 that Imperial College has licensed to them No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

The oral microbiome has been connected with lung health and may be of significance in the progression of SARS-CoV-2 infection. Saliva-based SARS-CoV-2 tests provide the opportunity to leverage stored samples for assessing the oral microbiome. However, these collection kits have not been tested for their accuracy in measuring the oral microbiome. Saliva is highly enriched with human DNA and reducing it prior to shotgun sequencing may increase the depth of bacterial reads. We examined both the effect of saliva collection method and sequence processing on measurement of microbiome depth and diversity by 16S rRNA gene amplicon and shotgun metagenomics. We collected 56 samples from 22 subjects. Each subject provided saliva samples with and without preservative, and a subset provided a second set of samples the following day. 16S rRNA gene (V4) sequencing was performed on all samples, and shotgun metagenomics was performed on a subset of samples collected with preservative with and without human DNA depletion before sequencing. We observed that the beta diversity distances within subjects over time was smaller than between unrelated subjects, and distances within subjects were smaller in samples collected with preservative. Samples collected with preservative had higher alpha diversity measuring both richness and evenness. Human DNA depletion before extraction and shotgun sequencing yielded higher total and relative reads mapping to bacterial sequences. We conclude that collecting saliva with preservative may provide more consistent measures of the oral microbiome and depleting human DNA increases yield of bacterial sequences., (© 2021. The Author(s).)

Background: The presence of symptomatic lumbar facet cysts has been associated with segmental instability. Given this association, decompression versus decompression with fusion is a frequently debated topic. Multiple grading scales have been devised to identify patients at high risk for development of cyst recurrence; however, there exists no external evaluation of these scales., Methods: A retrospective review of 54 patients undergoing initial treatment for lumbar synovial cysts at a single institution over the past 12 years was conducted. Surgical treatment consisted of decompression with cystectomy without fusion. Patients were assessed and classified according to the NeuroSpine Surgery Research Group (NSURG) and Rosenstock Classification systems. Five neurosurgeons reviewed the preoperative magnetic resonance images, and results were classified. Interrater reliability was assessed using both Gwet's AC1 coefficient and Krippendorff's alpha. A 1-way analysis of variance was used to evaluate predictive ability of both classification systems., Results: In total, of the 54 patients who underwent decompression, 7 had cyst recurrence. Overall cyst recurrence was most common in NSURG grade 2 cysts (3/12, 25%) followed by grade 1 cysts (4/27, 14.8%). Of the NSURG grade 3 and 4 patients, none had cyst recurrence. In the Rosenstock grades the most common recurrence was in grade 3 cysts (1/4, 25%) followed by grade 1 cysts (5/26, 19.2%). Interrater reliability demonstrated good reproducibility on Gwet's AC1 and Krippendorff's alpha on both grading scales. Neither score was predictive of cyst recurrence (P > 0.05)., Conclusions: The Rosenstock and NeuroSpine scores demonstrate good overall interrater reliability but are inconsistent in their ability to predict recurrence of lumbar facet cysts., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population., Methods: A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months., Results: Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4-3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels., Conclusions: In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection.Clinical Trials Registration. NCT04336215., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Tomato leaf curl New Delhi virus-potato (ToLCNDV-potato) causes potato apical leaf curl disease which severely affects nutritional parameters such as carbohydrate, protein, and starch biosynthesis thereby altering glycemic index (GI) and resistant starch (RS) of potato. ToLCNDV-potato virus was inoculated on potato cultivars (Kufri Pukhraj [susceptible]; Kufri Bahar [resistant]) and various quality parameters of potato tuber were studied. There was a significant (P < 0.01) reduction in starch, amylose and resistant starch contents in the infected tubers. However, carbohydrate and amylopectin increased significantly (P < 0.01) which contributes to increased starch digestibility reflected with high GI and glycemic load values. Besides, ToLCNDV-potato infection leads to a significant increase in reducing sugar, sucrose, amino acid and protein in potato tubers. This is a first-ever study that highlights the impact of biotic stress on GI, RS and nutritional quality parameters of potato which is a matter of concern for consumers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to compare patient-reported quality of life (QOL) scores after accelerated partial breast irradiation (APBI) using interstitial brachytherapy vs. external beam whole breast radiotherapy (WBRT) for breast cancer., Material and Methods: Women with breast cancer treated with WBRT or APBI after breast conservation surgery were enrolled in this prospective study. Single cross-sectional QOL assessment was performed using EORTC QLQ-C30 and BR-23 questionnaires. Patients treated with APBI were propensity-score matched to similar cohort of patients treated with WBRT. QOL scores were analyzed for the entire unmatched cohort and compared between the two matched cohorts using Student's two-tailed t -test. P -value of < 0.05 was considered statistically significant, and a 10-point difference between mean scores was considered clinically meaningful., Results: A total of 64 APBI patients were matched with 99 WBRT patients out of the entire study cohort of 320 cases. QOL scores for functional scales of QLQ-C30 were similar between the two groups for both matched and unmatched cohorts, while symptom scores of QLQ-C30 did not show any clinically significant difference. Functional scales of BR-23 did not show any clinical or statistically significant difference. Among symptom scales of BR-23, scores were similar for APBI and WBRT groups except for a worse score of "upset by hair loss" sub-scale in the brachytherapy group of the matched cohort (51.9 vs. 22.7, p = 0.006)., Conclusions: Patients undergoing APBI reported similar QOL compared to WBRT when matched for various factors., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

Breast cancer incidence is on the rise in India as in rest of the world. While the advances in overall cancer care are at par, the surgical interventions have not been changing at the same pace in India, as in the rest of the developed world. Partly, this is due to the relatively more advanced state of cancer at detection and partly due to lack of awareness resulting in apprehension and slow acceptance of de-escalation of surgical interventions by the treating surgeons, and the beneficiaries, the patients. The article looks at the current scenario, available evidence on the practices and pitfalls with possible solutions for advancing surgical care of breast cancer in India.

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud's disease, previous breast cancer, Barrett's oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Deep learning and its applications have gained tremendous interest recently in both academia and industry. Restricted Boltzmann machines (RBMs) offer a key methodology to implement deep learning paradigms. This brief presents a novel approach for realizing hybrid CMOS-memristive-based deep generative models (DGMs). In our proposed DGM architecture, HfO x -based (filamentary-type switching) memristive devices are extensively used for realizing both computational as well as storage functions, such as: 1) synapses (weights); 2) internal neuron-state storage; 3) stochastic neuron activation; and 4) programmable signal normalization. To validate the proposed scheme, we have simulated two different architectures: 1) deep belief network (DBN) for classification and 2) stacked denoising autoencoder for the reconstruction of handwritten digits from the MNIST data set. The maximum test accuracy achieved by pretraining of the proposed DBN was 92.6%, whereas the best case mean squared error (mse) achieved by pretraining of the proposed SDA network was 0.046. When the proposed model-based weights are used for weight initialization, they offer a significant advantage in terms of learning performance in comparison with randomized initialization.

Breast cancer is no longer considered a single disease, and with better understanding of cancer biology, its management has evolved over the years, into a complex individualized use of therapeutics based on variable expressions of predictive and prognostic factors. With the advent of molecular and genetic research, the complexity and diversity of breast cancer cells and their ability to survive and develop resistance to treatment strategies became more evident. At the same time, targeted therapies evolved, as specific targets were discovered such as HER2 receptor, and androgen receptor. More recent is the development of immunotherapy which aims at strengthening the host immune system to identify and kill the tumor cells. In breast cancer treatment, use of molecular tests has been a target of controversies, due to their high costs and inaccessibility in limited resource situations. Research in breast cancer is also proceeding at a rapid pace, but it is important to remember that breast cancer continues to be a complex interplay of alterations at molecular and genetic level, with the variability in expressions at protein level leading to difference in behavior and responses to treatment and overall outcome. In the succeeding paragraphs, we will try to review the available evidence in literature and attempt to understand the molecular complexity of breast cancer in order to simplify the art of treating the disease and improving outcomes., (© Indian Association of Surgical Oncology 2019.)

Background: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration., Methods: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC., Results: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones., Conclusion: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs., Competing Interests: Declaration of competing interest This manuscript has been read and approved by all the authors, the requirements for authorship have been met. We believe that the manuscript represents honest work and this information is not provided in another form., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD., Methods: This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks., Results: Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP)., Conclusion: Razumab™ (world's first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016-Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739.

Background: Cancer treatment during nationwide lockdown due to the COVID-19 pandemic has posed several challenges in the delivery of cancer care and carries tremendous potential sequel of impoverishing the households. This study aims to examine the economic distress faced by breast cancer patients receiving treatment at Tata Memorial Center (TMC) Mumbai, India during the nationwide lockdown initiated in March 2020 following the outbreak of COVID-19., Methods: A total of 138 non-metastatic breast cancer patients who were accrued in this study at TMC before imposing of lockdown, and their treatment was impacted because of the COVID-19 outbreak, were interviewed. Telephonic interviews were conducted using a structured schedule which contained information on household and demographic characteristics of the patients, knowledge about COVID-19, their daily expenditure for treatment, difficulties faced during lockdown and how they met expenditures. Descriptive statistics and logistic regression were used in the analyses., Results: The average monthly expenditure of cancer patients had increased by 32% during the COVID-19 period while the mean monthly household income was reduced by a quarter. More than two-thirds of the patients had no income during the lockdown. More than half of the patients met their expenditure by borrowing money, 30% of the patients used their savings, 28% got charity and 25% used household income. About 81% of the patients had reported shortage of money, 32%  reported shortage of food and 28% reported shortage of medicine. The distress financing was significantly higher among patients receiving treatment in Mumbai compared to those receiving treatment at their native cities (67% vs. 46%), patients under 40 years of age, illiterate, currently married, Muslim and staying at a rented house., Conclusion: The incremental expenditure coupled with reduced or no income due to the closure of economic activities in the country imposed severe financial stress on breast cancer patients.

Purpose: Quality of life has become an integral aspect of the management of breast cancer. Many women still need to undergo a modified radical mastectomy (MRM). Factors affecting the choice a woman makes to undergo breast reconstruction (BR) are unclear and are hypothesized to be influenced by socioeconomic factors. We conducted a survey to evaluate the awareness and acceptability of BR among women with breast cancer at our institution., Methods: A novel questionnaire was designed and served to 3 groups of women: planned for MRM, follow up (FU) post-MRM, and FU post breast-conserving surgery., Results: Responses were analyzed from 492 women. Of these, 280 (56.91%) were planned for MRM and 212 (43.08%) women were on FU. Almost 45% women were older than 50 years of age, and literacy rate was 87.6%. More than 70% were homemakers and 15 women (3%) were unmarried. The aspects evaluating awareness of BR suggested that 251 (51.01%) women had knowledge about BR. Major source of information was the surgeon (45.81%) and media (32.87%). About 80% women on FU post-MRM did not want reconstruction, and 55% did not opt for BR as they had coped with the mastectomy and did not feel the need for BR. Only 6% cited family or financial reasons and 10% cited recurrence concerns. Among women planned for surgery, 65.71% had not considered BR. When questioned, 25 (12.88%) felt influenced by cost, 102 (52.58%) felt they did not need it, and 20 (10.31%) were worried it would affect treatment., Conclusion: Our study shows high awareness regarding BR, but only 27.89% women opt for BR independent of economic issues. We recommend all patients should be counseled about the reconstructive options when their MRM is planned.

Purpose: The purpose of the study was to report dosimetric differences for breast brachytherapy plans optimized for clinical target volume (CTV) generated using conventional isotropic expansion of tumor bed volume (TBV) and Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) recommendations to expand the TBV anisotropically to achieve a total safety margin of 2 cm (resection margin size + added safety margin)., Methods: Institutional records of 100 patients who underwent accelerated partial breast irradiation using multicatheter interstitial brachytherapy from May 2015 to March 2020 were reviewed retrospectively. Two sets of CT-based plans were made, one with 1-cm isotropic margins around the tumor bed (CTV&#95;ISO) and the other with anisotropic margins (CTV&#95;GEC). Plans were evaluated and compared using the American Brachytherapy Society and GEC-ESTRO guidelines., Results: The median TBV was 36.97 cc. The median margin widths were as follows: anterior 1.2, posterior 1.0, superior 1.0, inferior 0.9, medial 1.2, and lateral 1.2 cm. The mean tumor bed coverage index was 0.94; 0.93 [p.066], the CTV coverage index 0.86; 0.84 [p 0.001], the dose homogeneity index (DHI) 0.77; 0.75 [p < 0.001] and the conformity index 0.66; 0.64 [p < 0.001] in CTV&#95;ISO and CTV&#95;GEC plans, respectively. In smaller volume implants (TBV< 35 cc), the DHI was 0.76; 0.75 [p 0.008] and the conformity index was 0.66; 0.62 [p < 0.001], whereas in larger volumes >35 cc, the CTV coverage index was 0.86; 0.84 [p 0.003] and the DHI 0.78; 0.76 [p 0.001] in CTV&#95;ISO and CTV&#95;GEC plans, respectively., Conclusions: In this cohort of patients who underwent accelerated partial breast irradiation, plans with anisotropic margins had lower conformity, the impact of which was predominantly seen in smaller implants. Rest of the dosimetric constraints were achieved in both the plans as per the American Brachytherapy Society and GEC-ESTRO guidelines., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the performance of an AI-powered algorithm for the automatic detection of pulmonary embolism (PE) on chest computed tomography pulmonary angiograms (CTPAs) on a large dataset., Methods: We retrospectively identified all CTPAs conducted at our institution in 2017 (n = 1499). Exams with clinical questions other than PE were excluded from the analysis (n = 34). The remaining exams were classified into positive (n = 232) and negative (n = 1233) for PE based on the final written reports, which defined the reference standard. The fully anonymized 1-mm series in soft tissue reconstruction served as input for the PE detection prototype algorithm that was based on a deep convolutional neural network comprising a Resnet architecture. It was trained and validated on 28,000 CTPAs acquired at other institutions. The result series were reviewed using a web-based feedback platform. Measures of diagnostic performance were calculated on a per patient and a per finding level., Results: The algorithm correctly identified 215 of 232 exams positive for pulmonary embolism (sensitivity 92.7%; 95% confidence interval [CI] 88.3-95.5%) and 1178 of 1233 exams negative for pulmonary embolism (specificity 95.5%; 95% CI 94.2-96.6%). On a per finding level, 1174 of 1352 findings marked as embolus by the algorithm were true emboli. Most of the false positive findings were due to contrast agent-related flow artifacts, pulmonary veins, and lymph nodes., Conclusion: The AI prototype algorithm we tested has a high degree of diagnostic accuracy for the detection of PE on CTPAs. Sensitivity and specificity are balanced, which is a prerequisite for its clinical usefulness., Key Points: • An AI-based prototype algorithm showed a high degree of diagnostic accuracy for the detection of pulmonary embolism on CTPAs. • It can therefore help clinicians to automatically prioritize exams with a high suspection of pulmonary embolism and serve as secondary reading tool. • By complementing traditional ways of worklist prioritization in radiology departments, this can speed up the diagnostic and therapeutic workup of patients with pulmonary embolism and help to avoid false negative calls.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a critical concern among healthcare workers (HCWs). Other studies have assessed SARS-CoV-2 virus and antibodies in HCWs, with disparate findings regarding risk based on role and demographics., Methods: We screened 3904 employees and clinicians for SARS-CoV-2 virus positivity and serum immunoglobulin (Ig)G at a major New Jersey hospital from April 28 to June 30, 2020. We assessed positive tests in relation to demographic and occupational characteristics and prior coronavirus disease 2019 symptoms using multivariable logistic regression models., Results: Thirteen participants (0.3%) tested positive for virus and 374 (9.6%) tested positive for IgG (total positive: 381 [9.8%]). Compared with participants with no patient care duties, the odds of positive testing (virus or antibodies) were higher for those with direct patient contact: below-median patient contact, adjusted odds ratio (aOR) = 1.71 and 95% confidence interval [CI] = 1.18-2.48; above-median patient contact, aOR = 1.98 and 95% CI = 1.35-2.91. The proportion of participants testing positive was highest for phlebotomists (23.9%), maintenance/housekeeping (17.3%), dining/food services (16.9%), and interpersonal/support roles (13.7%) despite lower levels of direct patient care duties. Positivity rates were lower among doctors (7.2%) and nurses (9.1%), roles with fewer underrepresented minorities. After adjusting for job role and patient care responsibilities and other factors, Black and Latinx workers had 2-fold increased odds of a positive test compared with white workers. Loss of smell, taste, and fever were associated with positive testing., Conclusions: The HCW categories at highest risk for SARS-CoV-2 infection include support staff and underrepresented minorities with and without patient care responsibilities. Future work is needed to examine potential sources of community and nosocomial exposure among these understudied HCWs., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Epigenetic dysregulation is a common mechanism shared by molecularly and clinically heterogenous neurodegenerative diseases (NDs). Histone acetylation homeostasis, maintained by the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), is necessary for appropriate gene expression and neuronal function. Disruption of neural acetylation homeostasis has been implicated in multiple types of NDs including Alzheimer's disease (AD), yet mechanisms underlying alterations remain unclear. We show that like AD, disruption of Tip60 HAT/HDAC2 balance with concomitant epigenetic repression of common Tip60 target neuroplasticity genes occurs early in multiple types of Drosophila ND models such as Parkinson's Disease (PD), Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Repressed neuroplasticity genes show reduced enrichment of Tip60 and epigentic acetylation signatures at all gene loci examined with certain genes showing inappropriate HDAC2 repressor enrichment. Functional neuronal consequences for these disease conditions are reminiscent of human pathology and include locomotion, synapse morphology, and short-term memory deficits. Increasing Tip60 HAT levels specifically in the mushroom body learning and memory center in the Drosophila brain protects against locomotion and short-term memory function deficits in multiple NDs. Together, our results support a model by which Tip60 protects against neurological impairments in different NDs via similar modes of action.

Purpose: We tested low axillary sampling (LAS) and sentinel node biopsy (SNB) performed in the same patient to predict axillary nodal status post-neoadjuvant chemotherapy (NACT) in women undergoing elective breast surgery, clinically N0 after NACT., Patients and Methods: A total of 751 women clinically node negative post-NACT underwent LAS (excision of lymph node [LN] and fat below first intercostobrachial nerve). Of these women, 730 also underwent SNB by dual technique (methylene blue plus radioisotope). SNB (defined as targeted plus palpable LNs) and LAS specimens were distinctly examined for metastasis. All patients underwent completion axillary lymph node dissection. Post-NACT, 290 (38.6%) of 751 women had residual positive lymph nodes on pathology., Results: The median clinical tumor size was 5 cm (range, 1-15 cm), and 533 (71%) of patients were N1 or N2 at presentation. Targeted sentinel node (SN) identification was 85.7% (626 of 730; median, two LNs); SN with palpable nodes was found in 95.2% (695 of 730; median, five LNs); LAS node was identified in 98.5% (740 of 751; median, seven LNs). In all but one case, the SN was found within the LAS specimen. The false negative rate (FNR) of SNB (blue, hot, and adjacent palpable nodes) was 19.7% (47 of 238; one-sided 95% CI upper limit, 24.0), compared with an FNR of 9.9% for LAS (29 of 292; one-sided 95% CI upper limit, 12.8; P < .001). If SNB was confined to blue/hot node, excluding adjacent palpable nodes, the FNR was 31.6% (74 of 234; one-sided 95% CI upper limit, 36.6). The FNR could be brought down to < 8.8% if three or more LNs were identified by LAS., Conclusion: LAS is superior to SNB in identification rate, FNR, and negative predictive value in predicting node-negative axilla post-NACT. LAS can be safely used to predict negative axilla with < 10% chance of leaving residual disease.

Background: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots., Methods: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020., Findings: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection., Interpretation: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India., Competing Interests: The authors report no conflicts of interest.Each author has contributed sufficiently for construction of this manuscript., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: It can sometimes be challenging to find a suitable clip to treat an unusual aneurysm, or when the surrounding anatomy is unusual, especially in resource-limited environments. We describe a method to modify aneurysm clips based on the method originated by Sugita et al in 1985. Herein clip modification (Clip-Mod) is used to treat anatomically difficult anterior communicating artery aneurysms., Methods: The Department of Neurological Surgery database was reviewed to find aneurysm patients treated using modified aneurysm clips. Clip-Mod was performed during surgery by shortening the tines of titanium aneurysm clips by abrasion applied from the side of a standard 3-mm surgical diamond drill bit under constant irrigation. Note that the thickness of the tines and the clip spring were not modified or contacted by the drill., Results: Four cases used modified aneurysm clips, from 648 total clip-treated aneurysms (0.6%) by 2 surgeons over a 14-year period. Three patients presented with subarachnoid hemorrhages that were determined to be due to anterior communicating artery aneurysms. One patient presented with an incidental unruptured anterior communicating artery aneurysm. All 4 patients were treated with 3-mm titanium clips shortened intraoperatively to 1- to 2-mm lengths, to achieve aneurysm obliteration without stenosing parent or perforating vessels., Conclusions: All 4 patients have done well clinically with no reoccurrences after 2-6 years' follow-up, which included angiographic evaluation. The use of this "Clip-Mod" technique thus appears useful for anterior communicating artery aneurysms. Clip-Mod could also be considered for treating other aneurysms when the "perfect" length clip is not available., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the diagnostic performance of a deep learning-based algorithm for automated detection of acute and chronic rib fractures on whole-body trauma CT., Materials and Methods: We retrospectively identified all whole-body trauma CT scans referred from the emergency department of our hospital from January to December 2018 (n = 511). Scans were categorized as positive (n = 159) or negative (n = 352) for rib fractures according to the clinically approved written CT reports, which served as the index test. The bone kernel series (1.5-mm slice thickness) served as an input for a detection prototype algorithm trained to detect both acute and chronic rib fractures based on a deep convolutional neural network. It had previously been trained on an independent sample from eight other institutions (n = 11455)., Results: All CTs except one were successfully processed (510/511). The algorithm achieved a sensitivity of 87.4% and specificity of 91.5% on a per-examination level [per CT scan: rib fracture(s): yes/no]. There were 0.16 false-positives per examination (= 81/510). On a per-finding level, there were 587 true-positive findings (sensitivity: 65.7%) and 307 false-negatives. Furthermore, 97 true rib fractures were detected that were not mentioned in the written CT reports. A major factor associated with correct detection was displacement., Conclusion: We found good performance of a deep learning-based prototype algorithm detecting rib fractures on trauma CT on a per-examination level at a low rate of false-positives per case. A potential area for clinical application is its use as a screening tool to avoid false-negative radiology reports., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

Purpose: The role of axillary conservation after neoadjuvant chemotherapy (NACT) is debatable. We routinely carry out complete axillary lymph node dissection (ALND). This study was conducted to understand the pathologic axillary complete response (pAxCR) after NACT., Materials and Methods: We evaluated a prospective database of patients with breast cancer who underwent surgery after NACT in the year 2017 at our institution. NACT was administered to downstage locally advanced breast cancer or facilitate breast-conservation surgery., Results: Of 793 patients who underwent surgery after NACT, 97(12.2%) had cN0 disease, 407 (51.3%) had cN1, 262 (32%) had cN2, and 27 (3.4%) had cN3 at presentation. Eighty-eight patients (11.1%) had cT1-2 primary tumor stage, and 623 patients (78.6%) had cT3-4 primary tumor stage; primary tumor stage details were unavailable for 82 patients (10.3%). The median age was 46 years (range, 21-74 years). On histopathology, the overall pAxCR rate was 52.8%. In the cN1 and cN2 settings, 58.7% and 36.6% of patients achieved ypN0 status, respectively. The overall pathologic complete response rate was 22.64% (161 of 711 patients). On univariable analysis, cN stage, histologic grade, hormone receptor status, NACT duration, and lymphovascular invasion were significantly associated with pAxCR ( P <.001). On logistic regression, prechemotherapy cN status (odds ratio [OR], 3.08; 95% CI, 2.18 to 4.37; P <.001), estrogen and progesterone receptor status (OR, 0.34; 95% CI, 0.3 to 0.4; P <.001), and administration of both chemotherapy regimens preoperatively (OR, 0.66; 95% CI, 0.45 to 0.97; P <.05) predicted pAxCR., Conclusion: At least half of patients with cN1 and a third of patients with cN2 breast cancer who develop pAxCR may be suitable candidates for axillary conservation. A careful postchemotherapy assessment followed by a conservative axillary procedure may be an alternative to ALND, but this needs to be studied prospectively.