Can Artificial Intelligence Beat Humans in Detecting Breast Malignancy on Mammograms?

BACKGROUND: The study was aimed at identifying how useful Computer-Aided Detection (CAD) could be in reducing false-negative reporting in mammography and early detection of breast cancer at an early stage as the best protection is early detection. MATERIALS AND METHODS: This retrospective study was conducted in a tertiary care setup of Atomic Energy Cancer Hospital, Nuclear Medicine, Oncology and Radiotherapy Institute (AECH-NORI), where 33 patients with suspicious findings on mammography and subsequent biopsy-proven malignancy were included. The findings of mammography including the lesion type, breast parenchymal density, and sensitivity of CAD detection, as well as the final biopsy results, were recorded. A second group of 40 normal screening mammograms was also included who had no symptoms, had Breast Imaging-Reporting and Data System category I(BI-RADS I) mammograms, and had no pathology identified on correlative sonomammography as well. RESULTS: A total of 35 masses, 11 pleomorphic clusters of microcalcification, five clustered foci of macrocalcification, and nine lesions with pleomorphic clusters of microcalcification and two with pleomorphic clusters of microcalcification only were included. The CAD system was able to identify 26 masses (74%), eight lesions with pleomorphic clusters of microcalcification (72%), five foci of macrocalcification (100%), six lesions with pleomorphic clusters of microcalcification (66%), and two pleomorphic clusters of microcalcification without formed mass (100%). The overall sensitivity of the CAD system was 75.8%. CAD was able to identify 13 out of 16 masses with invasive ductal carcinoma (81.3%), eight out of nine lesions proven as invasive ductal carcinoma with ductal carcinoma in situ (DCIS) (88.9%), two out of five masses with invasive lobular carcinoma (40%), four out of four masses with invasive mammary carcinoma (100%), and zero out of one lesion identified as medullary carcinoma (0%). There was 100% detection for pleomorphic clusters of microcalcification without formed mass with CAD marking two out of two mammograms. CONCLUSION: CAD performed better with combined lesions, accurately marked pleomorphic clusters of microcalcification, and identified small lesions in predominant fibrofatty parenchymal density but was not reliable in dense breast, areas of asymmetric increased density, summation artifacts, edematous breast parenchyma, and retroareolar lesions. It also performed poorly with ill-defined lesions of invasive lobular carcinoma. Human intelligence hence beats CAD for the diagnosis of breast malignancy in mammograms as per our experience.

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Duodenal ulcer perforation and its consequences.

Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.

Biosynthesizing Cassia fistula Extract-Mediated Silver Nanoparticles for MCF-7 Cell Lines Anti-Cancer Assay.

The unique consequence of green synthesis is that the mediator plant is able to release chemicals that are efficacious as reducing as well as stabilizing agents. In this work, the fruit pulp and leaf essences of Cassia fistula have been used to manufacture silver nanoparticles through the green synthesis technique. The sculpturing of nanoparticles was accomplished by utilizing the reduction phenomenon that ensued due to the reaction between plant essences and the precursor solution. These biosynthesized silver nanoparticles were examined, where we used scanning electron microscopy, UV-vis spectroscopy, and X-ray diffraction techniques as means to analyze the structure, optical properties, and crystalline behavior, respectively. The absorption spectra for fruit and leaf extracts obtained from the UV-vis analyses peaked at 401 and 397 nm, and these peaks imply the appearance of optical energy gaps of 2.12 and 2.58 eV, accompanying spherical shapes of particles with diameters in the ranges of 12-20 and 50-80 nm, respectively. These silver nanoparticles together with the adopted green technique have a vast array of applications, specifically in the biomedical realm. In particular, they are being used to treat several diseases and are manifested as strong anti-tumor agents to medicate MCF-7 breast cancer cell lines in order to minimize the cell growth rate depending on their concentrations.

Postoperative MR Imaging of the Knee Meniscus.

Surgery to treat a torn meniscus is a common orthopedic procedure, and radiologists are frequently asked to image patients with new or recurrent knee pain after meniscus surgery. However, surgery alters the MR imaging appearance of the meniscus, making the diagnosis of recurrent tear a diagnostic challenge. This article reviews relevant anatomy of the meniscus, surgical techniques used to treat meniscus tear, the roles of conventional MR imaging and MR arthrography to assess the postoperative meniscus, and the key MR imaging findings to distinguish the intact postoperative meniscus from recurrent tear.

Biosynthesis and Characterizations of Silver Nanoparticles from Annona squamosa Leaf and Fruit Extracts for Size-Dependent Biomedical Applications.

Green synthesis differs in the way that the plant produces chemicals that act as reducing and stabilizing agents, and by adopting this green synthesis, we have synthesized silver nanoparticles (AgNPs) from the leaf and fruit extracts of Annona squamosa (also known as Sharifa), where these extracts have played an important role as reducing and capping agents. The nanoparticles were synthesized as the consequence of a reduction that happened between plant extracts and the precursor solution. The prepared AgNPs were then characterized using scanning electron microscopy, UV-Visible spectroscopy, and X-ray diffraction to study their morphology, optical response, and crystallinity. A single distinctive absorption peak of colloidal AgNPs samples was observed at 430 nm and 410 nm for leaf and fruit extract samples, having an optical bandgap of 2.97 eV and 2.88 eV, respectively, with a spherical shape having a diameter in the range of 35-90 nm and 15-50 nm, respectively, whilst XRD studies supported the FCC cubic structure of the mediated AgNPs. These green synthesized AgNPs have a wide variety of uses, particularly in the biomedical domain, where they have the potential to treat numerous diseases and are reported to be efficient against antibacterial, anti-cancer, and anti-diabetic activities.

Perceptions of Arab men regarding female breast cancer screening examinations-Findings from a Middle East study.

OBJECTIVES: In the Middle East, Qatar in particular, the incidence of breast cancer has substantially increased in recent years, and is expected to double by 2030. This diagnosis also occurs at a later stage in the disease. Early detection along with proper treatment reduces radical mastectomy and mortality rates, yet only one-third of Arab women in Qatar participate in breast cancer screening (BCS) activities of any sort. Many women in the conservative Qatari society rely on male family members for support and protection. This study investigates the attitudes and perceptions of Arab men in regards to breast cancer screening and what they see as both incentives and barriers to women's participation in BCS activities. DESIGN: A qualitative methodology using purposive sampling technique was chosen in order to explore participant's attitudes, beliefs and health-related actions. Individual in-depth interviews with open-ended questions were conducted with 50 Arab men during October 2011 to May 2012. Data collection, analysis, and interpretation occurred simultaneously. NVivo 9, a qualitative data analysis software program was used to organize themes and subthemes. RESULTS: It was found that most men understood the importance of regular BCS in early detection of breast cancer. They felt they had an important role in encouraging the women in their lives to participate in BCS activities, but were adamant that any examination must be done by a female health care professional. Few knew details about screening guidelines in Qatar, but most had a basic knowledge of some screening activities. Most indicated an interest in learning more about BC and screening activities in order to better help and inform their female family members. CONCLUSION: Because Arab men perceive that their opinions and support are a major factor influencing female family members' participation in breast cancer screening, it is important that any program instituted to increase such screening participation be aimed at both men and women. More information is needed by both sexes as to the need for and benefits of regular screening activities, the techniques used, and the newly revised guidelines in Qatar. Such a program needs to be introduced in the near future in order to avert, at least partially, the expected doubling in breast cancer cases by 2030 in the Middle East.

Factors that influence awareness of breast cancer screening among Arab women in Qatar: results from a cross sectional survey.

BACKGROUND: Breast cancer is the most common cancer among women in the State of Qatar. Due to low participation in breast cancer screening (BCS) activities, women in Qatar are often diagnosed with breast cancer at advanced stages of the disease. Findings indicate that low participation rates in BCS activities are significantly related to women's low level of awareness of breast cancer screening. The objectives of this study were to: (1) determine the factors that influence Qatari women's awareness of breast cancer and its screening activities: and (2) to find ways to effectively promote breast cancer screening activities among Arabic speaking women in Qatar. MATERIALS AND METHODS: A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) female Qatari citizens and non-Qatari Arabic-speaking residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Outcome measures included participant awareness levels of the most recent national recommended guidelines of BCS, participation rates in BCS activities, and factors related to awareness of BCS activities. RESULTS: While most participants (90.7%) were aware of breast cancer, less than half had awareness of BCS practices (28.9% were aware of breast self-examination and 41.8% of clinical breast exams, while 26.4% knew that mammography was recommended by national screening guidelines. Only 7.6% had knowledge of all three BCS activities). Regarding BCS practice, less than one-third practiced BCS appropriately (13.9% of participants performed breast self-examination (BSE) monthly, 31.3% had a clinical breast exam (CBE) once a year or once every two years, and 26.9% of women 40 years of age or older had a mammogram once every year or two years). Awareness of BCS was significantly related to BCS practice, education level, and receipt of information about breast cancer and/or BCS from a variety of sources, particularly doctors and the media. CONCLUSIONS: The low levels of participation rates in BCS among Arab women in this study indicate a strong need to increase awareness of the importance of breast cancer screening in Qatari women. Without this awareness, compliance with the most recent breast cancer screening recommendations in Qatar will remain low. An increased effort to implement mass media and public health campaigns regarding the impact of breast cancer on women's health and the benefits of early detection of breast cancer must be coupled with an enhanced participation of health care providers in delivering this message to Qatar population.

Beliefs and attitudes about breast cancer and screening practices among Arab women living in Qatar: a cross-sectional study.

BACKGROUND: Despite rising breast cancer incidence and mortality rates, breast cancer screening (BCS) rates among women in Qatar remain low. Previous studies indicate the need to better understand the many complex beliefs, values, and attitudes that influence Arab women's health seeking behavior for the development of culturally appropriate and effective intervention strategies to address breast cancer in the Middle East. This study investigates beliefs, attitudes, and BCS practices of Arabic-speaking women in Qatar. METHODS: A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) Arabic-speaking female Qatari citizens and non-Qatari residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Associations between beliefs and BCS practice were estimated using chi-square tests and multivariate logistic regression analyses. Participants who adhered to BCS guidelines (BCS practice = Yes) were compared to those who did not (BCS practice = No). RESULTS: In addition to low levels of awareness and low participation rates in BCS, one quarter of the participants stated their doctors talked to them about breast cancer, and less than half of the women interviewed believed breast cancer can be prevented. Women who engaged in BCS practice were more likely to have a doctor who talked to them about breast cancer, to believe they were in good-excellent health, that cancer can be prevented, or that cancer might be hereditary. The majority wanted to know if they had cancer and felt their health care needs were being met. The main reasons given for not planning BCS were lack of a doctor's recommendation, fear, and embarrassment. CONCLUSIONS: These findings indicate that a variety of channels (health care providers, media, breast cancer survivors, community leaders) should be utilized to create culturally appropriate breast cancer intervention programs and increased awareness of breast cancer, BCS, and the benefits of early detection of breast cancer. Employment of these measures will reduce breast cancer mortality rates among Arabic-speaking women living in the State of Qatar.

Arab women's breast cancer screening practices: a literature review.

Breast cancer incidence and mortality rates are increasing in the Arab world and the involved women are often diagnosed at advanced stages of breast cancer. This literature review explores factors influencing Arab women's breast cancer screening behavior. Searched databases were: Medline, PubMed, Cochrane Database of Systematic Reviews, CINAHL Plus, Google Scholar, Index Medicus for WHO Eastern Mediterranean, and Asian Pacific Journal of Cancer Prevention. Breast cancer screening participation rates are low. Screening programs are opportunistic and relatively new to the region. Knowledge amongst women and health care providers, professional recommendation, socio-demographic factors, cultural traditions, beliefs, religious, social support, accessibility and perceived effectiveness of screening influence screening behavior.

Inducible NOS-induced chloride intracellular channel 4 (CLIC4) nuclear translocation regulates macrophage deactivation.

Nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions. Here we demonstrate that CLIC4 is induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages. Chemical inhibition or genetic ablation of iNOS inhibits S-nitrosylation and nuclear translocation of CLIC4. In macrophages, iNOS-induced nuclear CLIC4 coincides with the pro- to anti-inflammatory transition of the cells because IL-1ß and CXCL1 mRNA remain elevated in CLIC4 and iNOS knockout macrophages at late time points, whereas TNFα mRNA is elevated only in the iNOS knockout macrophages. Active IL-1ß remains elevated in CLIC4 knockout macrophages and in macrophages in which CLIC4 nuclear translocation is prevented by the NOS inhibitor l-NAME. Moreover, overexpression of nuclear-targeted CLIC4 down-regulates IL-1ß in stimulated macrophages. In mice, genetically null for CLIC4, the number of phagocytosing macrophages stimulated by LPS is reduced. Thus, iNOS-induced nuclear CLIC4 is an essential part of the macrophage deactivation program.

CLIC4 is a tumor suppressor for cutaneous squamous cell cancer.

Chloride intracellular channel (CLIC) 4 is a member of a redox-regulated, metamorphic multifunctional protein family, first characterized as intracellular chloride channels. Current knowledge indicates that CLICs participate in signaling, cytoskeleton integrity and differentiation functions of multiple tissues. In metabolically stressed skin keratinocytes, cytoplasmic CLIC4 is S-nitrosylated and translocates to the nucleus where it enhances transforming growth factor-ß (TGF-ß) signaling by protecting phospho-Smad 2 and 3 from dephosphorylation. CLIC4 expression is diminished in multiple human epithelial cancers, and the protein is excluded from the nucleus. We now show that CLIC4 expression is reduced in chemically induced mouse skin papillomas, mouse and human squamous carcinomas and squamous cancer cell lines, and the protein is excluded from the nucleus. The extent of reduction in CLIC4 coincides with progression of squamous tumors from benign to malignant. Inhibiting antioxidant defense in tumor cells increases S-nitrosylation and nuclear translocation of CLIC4. Adenoviral-mediated reconstitution of nuclear CLIC4 in squamous cancer cells enhances TGF-ß-dependent transcriptional activity and inhibits growth. Adenoviral targeting of CLIC4 to the nucleus of tumor cells in orthografts inhibits tumor growth, whereas elevation of CLIC4 in transgenic epidermis reduces de novo chemically induced skin tumor formation. In parallel, overexpression of exogenous CLIC4 in squamous tumor orthografts suppresses tumor growth and enhances TGF-ß signaling. These results indicate that CLIC4 suppresses the growth of squamous cancers, that reduced CLIC4 expression and nuclear residence detected in cancer cells is associated with the altered redox state of tumor cells and the absence of detectable nuclear CLIC4 in cancers contributes to TGF-ß resistance and enhances tumor development.

S-nitrosylation regulates nuclear translocation of chloride intracellular channel protein CLIC4.

Nuclear translocation of chloride intracellular channel protein CLIC4 is essential for its role in Ca(2+)-induced differentiation, stress-induced apoptosis, and modulating TGF-beta signaling in mouse epidermal keratinocytes. However, post-translational modifications on CLIC4 that govern nuclear translocation and thus these activities remain to be elucidated. The structure of CLIC4 is dependent on the redox environment, in vitro, and translocation may depend on reactive oxygen and nitrogen species in the cell. Here we show that NO directly induces nuclear translocation of CLIC4 that is independent of the NO-cGMP pathway. Indeed, CLIC4 is directly modified by NO through S-nitrosylation of a cysteine residue, as measured by the biotin switch assay. NO enhances association of CLIC4 with the nuclear import proteins importin alpha and Ran. This is likely a result of the conformational change induced by S-nitrosylated CLIC4 that leads to unfolding of the protein, as exhibited by CD spectra analysis and trypsinolysis of the modified protein. Cysteine mutants of CLIC4 exhibit altered nitrosylation, nuclear residence, and stability, compared with the wild type protein likely as a consequence of altered tertiary structure. Moreover, tumor necrosis factor alpha-induced nuclear translocation of CLIC4 is dependent on nitric-oxide synthase activity. Inhibition of nitric-oxide synthase activity inhibits tumor necrosis factor alpha-induced nitrosylation and association with importin alpha and Ran and ablates CLIC4 nuclear translocation. These results suggest that S-nitrosylation governs CLIC4 structure, its association with protein partners, and thus its intracellular distribution.

CLIC4, skin homeostasis and cutaneous cancer: surprising connections.

Chloride intracellular channel 4 (CLIC4) is a putative chloride channel for intracellular organelles. CLIC4 has biological activities in addition to or because of its channel activity. In keratinocytes, CLIC4 resides in the mitochondria and cytoplasm, and CLIC4 gene expression is regulated by p53, TNF-alpha, and c-Myc. Cytoplasmic CLIC4 translocates to the nucleus in response to cellular stress conditions including DNA damage, metabolic inhibition, senescence, and exposure to certain trophic factors such as TNF-alpha and LPS. Nuclear translocation is associated with growth arrest or apoptosis, depending on the level of expression. In the nucleus CLIC4 interacts with several nuclear proteins as demonstrated by yeast two-hybrid screening and co-immunoprecipitation. Nuclear CLIC4 appears to act on the TGF-beta pathway, and TGF-beta also causes CLIC4 nuclear translocation. In human and mouse cancer cell lines, CLIC4 levels are reduced, and CLIC4 is excluded from the nucleus. CLIC4 soluble or membrane-inserted status is dependent on redox state, and redox alterations in cancer cells could underly the defect in nuclear translocation. CLIC4 is reduced and excluded from the nucleus of many human epithelial neoplasms. Paradoxically, CLIC4 is reciprocally upregulated in tumor stroma in conjunction with the expression of alpha-smooth muscle actin in the fibroblast to myofibroblast transition. Overexpression of CLIC4 in cancer cells inhibits tumor growth in vivo. Conversely, overexpression of CLIC4 in tumor stromal cells stimulates tumor growth in vivo. Thus, CLIC4 participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation.