Non-cell-autonomous cancer progression from chromosomal instability.

Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.

Do psychiatric diseases follow annual cyclic seasonality?

Seasonal affective disorder (SAD) famously follows annual cycles, with incidence elevation in the fall and spring. Should some version of cyclic annual pattern be expected from other psychiatric disorders? Would annual cycles be similar for distinct psychiatric conditions? This study probes these questions using 2 very large datasets describing the health histories of 150 million unique U.S. citizens and the entire Swedish population. We performed 2 types of analysis, using "uncorrected" and "corrected" observations. The former analysis focused on counts of daily patient visits associated with each disease. The latter analysis instead looked at the proportion of disease-specific visits within the total volume of visits for a time interval. In the uncorrected analysis, we found that psychiatric disorders' annual patterns were remarkably similar across the studied diseases in both countries, with the magnitude of annual variation significantly higher in Sweden than in the United States for psychiatric, but not infectious diseases. In the corrected analysis, only 1 group of patients-11 to 20 years old-reproduced all regularities we observed for psychiatric disorders in the uncorrected analysis; the annual healthcare-seeking visit patterns associated with other age-groups changed drastically. Analogous analyses over infectious diseases were less divergent over these 2 types of computation. Comparing these 2 sets of results in the context of published psychiatric disorder seasonality studies, we tend to believe that our uncorrected results are more likely to capture the real trends, while the corrected results perhaps reflect mostly artifacts determined by dominantly fluctuating, health-seeking visits across a given year. However, the divergent results are ultimately inconclusive; thus, we present both sets of results unredacted, and, in the spirit of full disclosure, leave the verdict to the reader.

Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Metaplastic carcinoma of the breast: matched cohort analysis of recurrence and survival.

PURPOSE: Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer, defined as mammary carcinoma with squamous or mesenchymal differentiation, that may include spindle cell, chondroid, osseous, or rhabdomyoid differentiation patterns. The implications of MBC recurrence and survival outcomes remains unclear. METHODS: Cases were ascertained from a prospectively maintained institutional database of patients treated from 1998 to 2015. Patients with MBC were matched 1:1 to non-MBC cases. Cox proportional-hazards models and Kaplan-Meier estimates were used to evaluate outcome differences between cohorts. RESULTS: 111 patients with MBC were matched 1:1 with non-MBC patients from an initial set of 2400 patients. Median follow-up time was 8 years. Most patients with MBC received chemotherapy (88%) and radiotherapy (71%). On univariate competing risk regression, MBC was not associated with locoregional recurrence (HR = 1.08; p = 0.8), distant recurrence (HR = 1.65; p = 0.092); disease-free survival (HR = 1.52; p = 0.065), or overall survival (HR = 1.56; p = 0.1). Absolute differences were noted in 8-year disease-free survival (49.6% MBC vs 66.4% non-MBC) and overall survival (61.3% MBC vs 74.4% non-MBC), though neither of these reached statistical significance (p = 0.07 and 0.11, respectively). CONCLUSION: Appropriately-treated MBC may exhibit recurrence and survival outcomes that are difficult to distinguish from those of non-MBC. While prior studies suggest that MBC has a worse natural history than non-MBC triple-negative breast cancer, prudent use of chemotherapy and radiotherapy may narrow these differences, although studies with more power will be required to inform clinical management. Longer follow-up among larger populations may further elucidate the clinical and therapeutic implications of MBC.

Is Likert better than PI-RADS at predicting prostate cancer on MRI and can a mathematical algorithm achieve similar results?

BACKGROUND: Prostate Imaging Reporting & Data System (PI-RADS) is an internationally recognized system to quantify risk of prostate cancer on magnetic resonance imaging (MRI). However, studies have suggested methods to improve predictive accuracy. PURPOSE: To assess two different methods that aim to improve the accuracy of PI-RADS scores: a subjective Likert score given by experienced reporters, and an objective Calculated Adjustment of PI-RADS Equivocal Score (CAPES). MATERIAL AND METHODS: Five experienced reporters in a quaternary referral unit used a standardized reporting template to prospectively collect PI-RADS and Likert scores for 1467 multiparametric MRI (mpMRI) scans between January 2021 and June 2022. Histology results were recorded for patients who underwent trans-perineal biopsy. The CAPES tool was retrospectively applied to the cases scoring PI-RADS 3. A theoretical standardized biopsy protocol (assuming all patients scoring ≥3 were referred for biopsy) was used to compare the three scoring systems for sensitivity, specificity, and positive predictive value (PPV). RESULTS: Across all reporters, significantly fewer equivocal "3" scores were given using Likert (15.7%) or CAPES (2.2%) compared to PI-RADS (24.1%). Assuming a protocol where all patients scoring ≥3 were biopsied, Likert had a higher specificity (69.0% vs. 54.4%), sensitivity (98.3% vs. 97.7%), and PPV (49.9% vs. 40.3%) than PI-RADS for identifying ISUP ≥2 cancer. The CAPES tool had an even higher specificity (81.4%) and PPV (61.2%) with only a slightly lower sensitivity (93.4%) resulting in 37.1% (n = 316) fewer biopsies than PI-RADS, and 22.4% (n = 155) fewer biopsies than Likert across 1467 patients. CONCLUSIONS: Compared to PI-RADS scoring, Likert scoring or CAPES can result in fewer equivocal scores, greater PPV, and fewer unnecessary biopsies.

Roman Urdu Hate Speech Detection Using Transformer-Based Model for Cyber Security Applications.

Social media applications, such as Twitter and Facebook, allow users to communicate and share their thoughts, status updates, opinions, photographs, and videos around the globe. Unfortunately, some people utilize these platforms to disseminate hate speech and abusive language. The growth of hate speech may result in hate crimes, cyber violence, and substantial harm to cyberspace, physical security, and social safety. As a result, hate speech detection is a critical issue for both cyberspace and physical society, necessitating the development of a robust application capable of detecting and combating it in real-time. Hate speech detection is a context-dependent problem that requires context-aware mechanisms for resolution. In this study, we employed a transformer-based model for Roman Urdu hate speech classification due to its ability to capture the text context. In addition, we developed the first Roman Urdu pre-trained BERT model, which we named BERT-RU. For this purpose, we exploited the capabilities of BERT by training it from scratch on the largest Roman Urdu dataset consisting of 173,714 text messages. Traditional and deep learning models were used as baseline models, including LSTM, BiLSTM, BiLSTM + Attention Layer, and CNN. We also investigated the concept of transfer learning by using pre-trained BERT embeddings in conjunction with deep learning models. The performance of each model was evaluated in terms of accuracy, precision, recall, and F-measure. The generalization of each model was evaluated on a cross-domain dataset. The experimental results revealed that the transformer-based model, when directly applied to the classification task of the Roman Urdu hate speech, outperformed traditional machine learning, deep learning models, and pre-trained transformer-based models in terms of accuracy, precision, recall, and F-measure, with scores of 96.70%, 97.25%, 96.74%, and 97.89%, respectively. In addition, the transformer-based model exhibited superior generalization on a cross-domain dataset.

Examining the prevalence of homologous recombination repair defects in ER+ breast cancers.

PURPOSE: Homologous recombination deficiency (HRD) is well characterized in triple-negative breast cancer (TNBC), but its prevalence in the hormone-receptor-positive breast cancer subtypes is not as clearly defined. It is estimated that around 50-60% of TNBC cases are deficient in HR. We sought to identify HRD cases in ER+/Her2- patients using various mutational HRD signatures. METHODS: We abstracted published HRD genomic signatures from the Pan-Cancer Analysis of Whole Genomes (PCAWG) database and compared the prevalence of HRD in ER+/Her2- breast cancer, comparing this to the control of set of triple-negative breast cancers. RESULTS: In 78 patients with ER+/Her2- breast cancer, 13 patients have over a 70% probability of being HRD as measured by HRDetect, while 18 qualify as HRD based on HRD score, with an approximate prevalence of HRD ranging between 14 and 20% of cases. CONCLUSION: Our analyses suggest that 14% of ER+/Her2- patients may be HRD and therefore potentially eligible for treatments with HRD-directed therapies such as platinum agents and PARP inhibitors. As the ER+/Her2- subtype is the most common breast cancer subtype, this group of HRD patients is likely more sizable than that of HRD TNBC patients.

Omission of Intraoperative Frozen Section May Reduce Axillary Overtreatment Among Clinically Node-Negative Patients Having Upfront Mastectomy.

BACKGROUND: The growing use of postmastectomy radiation/regional nodal irradiation (PMRT) has resulted in many women receiving both axillary dissection (ALND) and PMRT, increasing lymphedema rates. After developing standardized PMRT criteria, we adopted a policy of ALND omission among cN0 patients with 1-2 positive sentinel nodes (+SLNs) requiring PMRT. We evaluated how often overtreatment with ALND+PMRT was avoided with this approach. METHODS: A retrospective review of a prospectively maintained database was performed beginning 1 year before policy adoption. Intraoperative SLN evaluation was routine pre- and post-policy. ALND was performed for SLN macrometastasis pre-policy, and selectively performed post-policy for 1-2 +SLNs based on PMRT criteria. ALND+PMRT was required for ≥ 3 +SLNs. RESULTS: From March 1, 2018 to November 30, 2020, a total of 2207 cT1-3N0 patients had mastectomy and 231 had +SLNs; 109 (47%) were treated pre-policy and 122 (53%) post-policy. Most (81%) had 1-2 +SLNs. There was no change in rates of ALND+PMRT (64% pre-policy vs. 58% post-policy, p = 0.09), including in patients with 1-2 +SLNs (61% vs. 51%, p = 0.20). Post-policy, ALND was omitted in 9 (7%) patients recognized intraoperatively as PMRT candidates; avoidable ALND was performed in 40 (33%) patients not identified as PMRT candidates until receipt of final pathology. Overall, had intraoperative SLN evaluation been deferred, only 5.7% of patients would have required completion ALND: 2.2% (n = 49/2207) for ≥ 3 +SLNs and 3.5% (n = 77/2207) for 1-2 +SLNs without PMRT indication. CONCLUSIONS: Most patients could have avoided ALND+PMRT if decision making was deferred until final pathology was available. Selective intraoperative SLN evaluation in cN0 patients having upfront mastectomy may reduce avoidable overtreatment.

Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark.

The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.

Effect of lumbar traction on discogenic low back pain using variable forces.

OBJECTIVE: To determine the effect of variable traction forces on discogenic low back pain. METHODS: The experimental study was conducted at the Department of Physical Medicine and Rehabilitation at the Combined Military Hospital, Okara, Pakistan, from July to December 2018, and comprised patients of low back pain who were randomised into group 1 treated with high-force lumbar traction, hot pack and lumbar stabilisation exercises, and group 2 treated with low-force lumbar traction, hot pack and lumbar stabilisation exercises. There were a 3 sessions per week for 3 weeks for a total of 9 sessions. Modified Oswestry disability index and visual analogue scale were used to measure outcomes. Data was analysed using SPSS 20. RESULTS: Of the 30 patients, there were 15(50%) in each of the two groups. There were 18(60%) females and 12(40%) males, with an overall mean age of 30±5.5 years. Also 18(60%) subjects were obese on the basis of body mass index.There was significant improvement in pain in both groups (p<0.05), while disability scores in group 1 showed more improvement compared to group 2 (p<0.05). Young age was significantly associated with better results (p<0.05). CONCLUSIONS: Use of variable force lumbar traction improved pain in discogenic low back pain, while high-force lumbar traction also reduced functional disability.

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

BACKGROUND: For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. METHODS: This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. RESULTS: There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. CONCLUSIONS: LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Salvage of locally recurrent breast cancer with repeat breast conservation using 45 Gy hyperfractionated partial breast re-irradiation.

PURPOSE: Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45 Gy administered in 30 fractions of 1.5 Gy twice-daily to the partial breast, "rePBI"). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy. METHODS: All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. RESULTS: The cohort included 34 patients with a median age of 65.8 (46.2-78.2) at the time of rePBI. At a median follow-up of 23.5 months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity (< 3 months) was radiation dermatitis (100%), and common grade 1-2 late toxicities (> 3 months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%). CONCLUSIONS: Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45 Gy administered in 30 1.5 Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Ultra-Short Fraction Schedules as Part of De-intensification Strategies for Early-Stage Breast Cancer.

Adjuvant radiation therapy (RT) following breast-conserving surgery (BCS) represents a standard approach for most patients treated with breast-conserving therapy (BCT) for early-stage breast cancer. The first-generation of adjuvant RT schedules delivered daily treatment to the whole breast over 5-7 weeks. Although efficacious, this presented patients with a protracted course of treatment, reducing compliance and quality of life. While hypofractionated whole-breast irradiation (WBI) has become the standard, and part of the second-generation of RT regimens, it still requires 3-4 weeks. Concurrently, partial-breast irradiation (PBI) has also been explored as a technique to complete RT in a much shorter time period (1-3 weeks). There are now seven trials confirming the efficacy of this shorter treatment approach compared with standard WBI. In an effort to further reduce treatment duration, ultra-short WBI and PBI regimens have recently emerged as the third-generation of breast radiation schedules, allowing for the completion of treatment in 5 days or less. With respect to WBI, recent data from the FAST-Forward trial (which evaluated five fractions of WBI delivered in 1 week) demonstrated no difference in clinical outcomes at 5 years, with limited difference in toxicity, compared with hypofractionated 3-week WBI. Regarding PBI, published data on five-fraction regimens delivered in 2 weeks have also demonstrated comparable outcomes at 10 years, with reduced toxicities with long-term follow-up. This report will review additional ongoing studies evaluating even shorter courses of adjuvant RT treatment (one to five fractions), including single-fraction PBI or WBI.

Outcomes with Partial Breast Irradiation vs. Whole Breast Irradiation: a Meta-Analysis.

BACKGROUND: Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques. METHODS: A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI. RESULTS: A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI. CONCLUSIONS: IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

Dawn of a new era of antibody-drug conjugates and bispecific T-cell engagers for treatment of multiple myeloma: a systematic review of literature.

Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment.

Measurable health effects associated with the daylight saving time shift.

The transition to daylight saving time (DST) is beneficial for energy conservation but at the same time it has been reported to increase the risk of cerebrovascular and cardiovascular problems. Here, we evaluate the effect of the DST shift on a whole spectrum of diseases-an analysis we hope will be helpful in weighing the risks and benefits of DST shifts. Our study relied on a population-based, cross-sectional analysis of the IBM Watson Health MarketScan insurance claim dataset, which incorporates over 150 million unique patients in the US, and the Swedish national inpatient register, which incorporates more than nine million unique Swedes. For hundreds of sex- and age-specific diseases, we assessed effects of the DST shifts forward and backward by one hour in spring and autumn by comparing the observed and expected diagnosis rates after DST shift exposure. We found four prominent, elevated risk clusters, including cardiovascular diseases (such as heart attacks), injuries, mental and behavioral disorders, and immune-related diseases such as noninfective enteritis and colitis to be significantly associated with DST shifts in the United States and Sweden. While the majority of disease risk elevations are modest (a few percent), a considerable number of diseases exhibit an approximately ten percent relative risk increase. We estimate that each spring DST shift is associated with negative health effects-with 150,000 incidences in the US, and 880,000 globally. We also identify for the first time a collection of diseases with relative risks that appear to decrease immediately after the spring DST shift, enriched with infections and immune system-related maladies. These diseases' decreasing relative risks might be driven by the documented boosting effect of a short-term stress (such as that experienced around the spring DST shift) on the immune system.

Covid-19 lockdown: A greater impact on women.

It is well-documented that during a war, a natural disaster or a pandemic, women bear the worse brunt of the crisis. Worldwide, mental stress, domestic violence and cybercrime against women are widespread and under-reported during Covid-19. Creating boundaries in such situations is extremely important. It is imperative that policy-makers adopt a gender perspective to understand and analyse the effects of the pandemic and the lockdown on the economy, livelihoods and social structures. United Nations has called for urgent action and for governments to put women's safety first as they respond to the pandemic.

Recent Advances in Molten-Carbonate Membranes for Carbon Dioxide Separation: Focus on Material Selection, Geometry, and Surface Modification.

Membranes for carbon dioxide permeation have been recognized as potential candidates for CO2 separation technology, particularly in the energy sector. Supported molten-salt membranes provide ionic routes to facilitate carbon dioxide transport across the membrane, permit the use of membrane at higher temperature, and offer selectivity based on ionic affinity of targeted compound. In this review, molten-carbonate ceramic membranes have been evaluated for CO2 separation. Various research studies regarding mechanisms of permeation, properties of molten salt, significance of material selection, geometry of support materials, and surface modifications have been assessed with reference to membrane stabilities and operational flux rates. In addition, the outcomes of permeation experiments, stability tests, selection of the compatible materials, and the role of interfacial reactions for membrane degradation have also been discussed. At the end, major challenges and possible solutions are highlighted along with future recommendations for fabricating efficient carbon dioxide separation membranes.