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Introduction: In Nepal, breast cancer is the second most common cancer accounting for a large number of deaths.The subtype Triple-negative breast cancer (TNBC) is linked to poor prognosis and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). This study describes the outcome of women with TNBC as compared to other breast cancers in Bir Hospital in Nepal. Methods: This was a cross-sectional study conducted in Bir Hospital, National Academy of Medical Sciences. The breast cancer data in Department of Surgery and Department of Oncology were collected from July 2021 to June 2024. The study data on demographic details, clinical findings, radiological and pathological investigations, operative procedures, neoadjuvant/adjuvant therapy, surgical and oncological outcomeswere collected. The study approval was taken from Institutional Review Board of National Academy of Medical Sciences. Results: There were 72 breast cancer patientsout of which 10 (13.8 %) were TNBC. Majority of the cases (70%) underwent modified radical mastectomy and 60% of them had received neoadjuvant therapy in TNBC cases. One out of 10 had positive margin post mastectomy. The proportion of TNBC patients with postoperative wound infection, seroma and flap necrosis were 10% each. The mean lymph node positivity was less in TNBC group as compared to other breast cancers.There was one recurrence, one metastasis and no mortality till one year follow up. Conclusion: The surgical outcome was satisfactory and with neo-adjuvant, surgery and adjuvant therapy, there is less tumor recurrence and satisfactory disease free survival and overall survival.

Human gut microbiomes (microbiotas) are highly individualistic in taxonomic composition but nevertheless are functionally similar. Thus, collectively, they comprise a “metacommunity.” In ecological terminology, the assembly of human gut microbiomes is influenced by four processes: selection, speciation, drift, and dispersal. As a result of fortuitous events associated with these processes, individual microbiomes are taxonomically “tailor-made” for each host. However, functionally they are “off-the-shelf” because of similar functional outputs resulting from metabolic redundancy developed in host-microbe symbiosis. Because of this, future microbiological and molecular studies of microbiomes should emphasize the metabolic interplay that drives the human gut metacommunity and that results in these similar functional outputs. This knowledge will support the development of remedies for specific functional dysbioses and hence provide practical examples of precision medicine.

BackgroundThere is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study.MethodsNewly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]).ResultsWe recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

Objective To review the efficacy and safety of low-dose versus standard-dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.Methods and analysis Keyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide. Searches were limited to original full-text and English-language studies. Key outcomes included overall survival (OS), progression-free survival (PFS), prostate-specific antigen response and treatment-related adverse events. The review was performed in accordance with Cochrane Rapid Reviews Methods Group guidelines.Results Ten studies were identified that met the eligibility criteria: five phase I studies, two post-hoc analyses of phase III trials and three retrospective analyses. No consistent association between OS, PFS and drug dose was identified. Fewer severe treatment-related adverse events were observed at lower drug doses.Conclusion This review provides evidence that enzalutamide, apalutamide or darolutamide could be given at a lower than the standard recommended dose without loss of antitumour activity. A prospective near-equivalence randomised trial should be undertaken to compare registered and lower doses of these agents.PROSPERO registration number CRD42023440371.

Abstract Background Novel and comprehensive approaches are needed to address shortcomings in the diversity and inclusiveness of the scientific workforce. In response to this need and informed by multiple programs and data sources, we created the Research Scholars Program (RSP). The RSP is a yearlong program for early-career faculty with an overall objective to overcome barriers to the academic success, retention, progression, and promotion of groups underrepresented in biomedical and behavioral research. The goal of the RSP is to increase research confidence and productivity, build a supportive research community, and reduce isolation by providing personal and group research enrichment to junior faculty through professional development, mentorship, and networking. Methods We adapted evidence-based approaches for our institutional context and vetted the RSP across our campus. The resulting RSP consists of three main elements: (1) five levels of Mosaic Mentorship; (2) group and tailored professional development programming; and (3) scientific and social networking. To determine the potential of the RSP to improve research confidence critical to success, we used a modified shortened version of the Clinical Research Appraisal Inventory (CRAI-12) to assess participants’ confidence in performing a variety of research tasks before and after program participation. We collected information about retention, promotion, and grants submitted and awarded. Additionally, we conducted semi-structured exit interviews with each scholar after program participation to identify programmatic strengths and areas for improvement. Data for Cohorts 1 and 2 (N = 12) were analyzed. Results Our assessment finds, with one exception, increasing confidence in participants’ research skills across all items, ranging from 0.4 (4.7%) to 2.6 (40.6%). In their exit interviews, the Research Scholars (RS) described their improved productivity and increased sense of belonging and support from others. Research Scholars noted numerous components of the RSP as strengths, including the Mosaic Mentorship model, professional development programming, and opportunities for both informal and formal interactions. Respondents identified time pressure, a lack of feedback, and unclear expectations of the various mentorship roles as areas in which the program can improve. Conclusion Preliminary findings indicate that the RSP is successful in building the research confidence of underrepresented and disadvantaged early-career faculty. While this report focuses on the development and protocol of the RSP, additional cohorts and data will provide the evidence base to support dissemination as a national model of research professional development. Such programming is critical to ensure sustainable support structures, institutional networks, infrastructure, and resources that will improve discovery and equity through inclusive excellence.

This article argues for the importance of labor education in fighting the climate crisis, a vital form of education too often overlooked in the climate movement. Drawing on a case study of unionized culture workers in the United Kingdom, the article seeks to show the distinctive embedded nature of labor education. Success of labor education on the climate crisis hinges not so much on a particular pedagogy or curriculum in any one classroom setting, but on the ways in which a range of formal and informal educational actors and spaces work together across the labor and environmental movements, as part of a mobilizing project that seeks to link worker interests directly to the climate crisis, and identify actions that workers can take to address the crisis effectively. Labor education has a central role to play in ensuring a just transition in the move away from a fossil fuel based economy.

A growing number of climate activists and scholars argue that an effective climate movement needs the involvement of the trade union movement, to be able to push forward the radical social transformations required to address the global climate crisis. This article analyses the recent focus on climate adaptation in labour education and action by trade unions in the UK. Climate adaptation is inherently political, and this article analyses the agendas driving the turn to adaptation, the possibilities that adaptation strategies open up, and some of their risks and limitations. Climate adaptation strategies, the article argues, could represent an important step forward for developing effective labour education and action on the climate crisis, but only if these strategies enable unions to mobilize a focus on the root causes of the crisis, agitate for structural change, and attend to the global and not just local concerns of worker, social and climate justice.

ABSTRACTObesity is a complex, multifactorial condition that is an important risk factor for noncommunicable diseases including cardiovascular disease and type 2 diabetes. While prevention and management require a healthy and energy balanced diet and adequate physical activity, the taxonomic composition and functional attributes of the colonic microbiota may have a supplementary role in the development of obesity. The taxonomic composition and metabolic capacity of the fecal microbiota of 286 women, resident in Auckland New Zealand, was determined by metagenomic analysis. Associations with BMI (obese, nonobese), body fat composition, and ethnicity (Pacific, n = 125; NZ European women [NZE], n = 161) were assessed using regression analyses. The fecal microbiotas were characterized by the presence of three distinctive enterotypes, with enterotype 1 represented in both Pacific and NZE women (39 and 61%, respectively), enterotype 2 mainly in Pacific women (84 and 16%) and enterotype 3 mainly in NZE women (13 and 87%). Enterotype 1 was characterized mainly by the relative abundances of butyrate producing species, Eubacterium rectale and Faecalibacterium prausnitzii, enterotype 2 by the relative abundances of lactic acid producing species, Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus ruminis, and enterotype 3 by the relative abundances of Subdoligranulum sp., Akkermansia muciniphila, Ruminococcus bromii, and Methanobrevibacter smithii. Enterotypes were also associated with BMI, visceral fat %, and blood cholesterol. Habitual food group intake was estimated using a 5 day nonconsecutive estimated food record and a 30 day, 220 item semi-quantitative Food Frequency Questionnaire. Higher intake of ‘egg’ and ‘dairy’ products was associated with enterotype 3, whereas ‘non-starchy vegetables’, ‘nuts and seeds’ and ‘plant-based fats’ were positively associated with enterotype 1. In contrast, these same food groups were inversely associated with enterotype 2. Fecal water content, as a proxy for stool consistency/colonic transit time, was associated with microbiota taxonomic composition and gene pools reflective of particular bacterial biochemical pathways. The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes, most likely due to differential dietary intake and fecal consistency/colonic transit time. These parameters need to be considered in future analyses of human fecal microbiotas.

Abstract Background There is little information about cancer‐related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15–39 years old) due to its rare incidence. Here, we present the pre‐treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. Methods Newly diagnosed AYAC and age‐matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre‐treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self‐perceived cognitive ability assessed by FACT‐Cog v3 and biomarkers (inflammatory cytokines and brain‐derived neurotrophic factor [BDNF]). Results We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE−/− mice and apoE−/− mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; “apoE−/− SAA-TKO”) with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of CETP expression or SAA genotype on plasma lipids or inflammatory markers. Atherosclerotic lesion area in the aortic arch of apoE−/− mice was 5.9 ± 1.2%; CETP expression significantly increased atherosclerosis in apoE−/− mice (13.1 ± 2.2%). However, atherosclerotic lesion area in the aortic arch of apoE−/− SAA-TKO mice (5.1 ± 1.1%) was not significantly increased by CETP expression (6.2 ± 0.9%). The increased atherosclerosis in apoE−/− mice expressing CETP was associated with markedly increased SAA immunostaining in aortic root sections. Thus, SAA augments the atherogenic effects of CETP, which suggests that inhibiting CETP may be of particular benefit in patients with high SAA.

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D or chronic LD shift conditions for 12 weeks and fed low-fat diet. In the chronic LD shift condition, the light-dark cycle was advanced by 6 h every week. We found that chronic LD shifts exacerbated atherosclerosis in female, but not male, ApoE−/− mice. In females, chronic LD shifts increased total serum cholesterol concentrations with increased atherogenic VLDL/LDL particles. Chronic LD shifts did not affect food intake, activity, or body weight in male or female ApoE−/− mice. We also examined eating behavior in female ApoE−/− mice since aberrant meal timing has been linked to atherosclerosis. The phases of eating behavior rhythms, like locomotor activity rhythms, gradually shifted to the new LD cycle each week in the chronic LD shift group, but there was no effect of the LD shift on the amplitudes of the eating rhythms. Moreover, the duration of fasting intervals was not different in control 12L:12D compared to chronic LD shift conditions. Together these data demonstrate that female ApoE−/− mice have increased atherosclerosis when exposed to chronic LD shifts due to increased VLDL/LDL cholesterol, independent of changes in energy balance or feeding-fasting cycles.

Human gut microbiomes (microbiotas) are highly individualistic in taxonomic composition but nevertheless are functionally similar. Thus, collectively, they comprise a "metacommunity." In ecological terminology, the assembly of human gut microbiomes is influenced by four processes: selection, speciation, drift, and dispersal. As a result of fortuitous events associated with these processes, individual microbiomes are taxonomically "tailor-made" for each host. However, functionally they are "off-the-shelf" because of similar functional outputs resulting from metabolic redundancy developed in host-microbe symbiosis. Because of this, future microbiological and molecular studies of microbiomes should emphasize the metabolic interplay that drives the human gut metacommunity and that results in these similar functional outputs. This knowledge will support the development of remedies for specific functional dysbioses and hence provide practical examples of precision medicine. [ABSTRACT FROM AUTHOR]

Background/Objectives: To assess associations between dietary fibre intake, adiposity, and odds of metabolic syndrome in Pacific and New Zealand European women. Methods: Pacific (n = 126) and New Zealand European (NZ European; n = 161) women (18–45 years) were recruited based on normal (18–24.9 kg/m2) and obese (≥30 kg/m2) BMIs. Body fat percentage (BF%), measured using whole body DXA, was subsequently used to stratify participants into low (<35%) or high (≥35%) BF% groups. Habitual dietary intake was calculated using the National Cancer Institute (NCI) method, involving a five-day food record and semi-quantitative food frequency questionnaire. Fasting blood was analysed for glucose and lipid profile. Metabolic syndrome was assessed with a harmonized definition. Results: NZ European women in both the low- and high-BF% groups were older, less socioeconomically deprived, and consumed more dietary fibre (low-BF%: median 23.7 g/day [25–75-percentile, 20.1, 29.9]; high-BF%: 20.9 [19.4, 24.9]) than Pacific women (18.8 [15.6, 22.1]; and 17.8 [15.0, 20.8]; both p < 0.001). The main source of fibre was discretionary fast foods for Pacific women and whole grain breads and cereals for NZ European women. A regression analysis controlling for age, socioeconomic deprivation, ethnicity, energy intake, protein, fat, and total carbohydrate intake showed an inverse association between higher fibre intake and BF% (β= −0.47, 95% CI = −0.62, −0.31, p < 0.001), and odds of metabolic syndrome (OR = 0.91, 95% CI = 0.84, 0.98, p = 0.010) among both Pacific and NZ European women (results shown for both groups combined). Conclusions: Low dietary fibre intake was associated with increased metabolic disease risk. Pacific women had lower fibre intakes than NZ European women. [ABSTRACT FROM AUTHOR]

Fossil fuel corporations play a significant role in promoting their interests in schools and other educational institutions, a practice that has recently been labelled as 'petro-pedagogy.' But this role goes beyond the production of the pro-petroleum and anti-science corporate propaganda that tends to attract the most critical attention. In this article, I present a case study of the involvement of BP, one of the world's largest fossil fuel corporations, in primary and secondary education in the United Kingdom. As practiced by BP, petro-pedagogy constitutes a core part of a corporate education reform network that, for the past decade, has focused on promoting a neoliberal model of STEM education in schools around the world. This model, based on corporate and capitalist interests, poses a significant threat to our collective efforts to tackle the global climate crisis.

BackgroundIn advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics.ObjectiveTo present the report of APCCC 2017.Design, setting, and participantsTen important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process.Results and limitationsVoting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data.ConclusionsThe presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them.Patient summaryThe second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process.