Miracle-dz/UniFAR-FTUs huggingface dataset:
Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen

Simple Summary Approximately 15–25% of breast cancers are human epidermal growth factor receptor 2 (HER2)-positive. With the progress in medicine, promising results have been shown by dual targeted therapy with new drugs in the neoadjuvant setting. In our study, we compared the effectiveness of three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) for HER2-positive early breast cancer. The pathological complete response (pCR) rate was 55.6% in the TCH + Py cohort, 32.7% in the TCH cohort, and 56.6% in the TCHP cohort. The pCR rate was higher with TCH + Py than with TCH. There was no significant difference in pCR rate between the TCH + Py and TCHP cohorts. Abstract (1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181–0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554–1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.
Entrepreneurial competencies and performance of Ugandan SMEs: the mediating role of firm capabilities

Abstract The purpose of this study was twofold; (1) to establish the direct influence of Entrepreneurial competencies and Firm capability on SME Performance and (2) to examine the mediating role of Firm capability between Entrepreneurial competencies and SME Performance. A cross-sectional and explanatory design was utilized to collect and analyze data from 314 SMEs in Uganda. The sample size was proportionally distributed amongst three SME subsectors; manufacturing, trade, and restaurants. A positive and significant influence of entrepreneurial competencies and firm capabilities on SME performance was established. Among the seven entrepreneurial competencies understudy, innovative competency is highly associated with SME performance than other competencies. Interestingly, firm capabilities were found to be a powerful predictor of SME performance than entrepreneurial competencies. In addition, a partial and significant mediating role of firm capabilities was also found. Theoretically, the study provides maiden evidence of the indirect influence of a firm’s capabilities on the association between entrepreneurial competencies and SME performance. In practice, managers and SME owners should address their competency deficiencies to develop more capabilities like management and marketing capabilities which could enhance SME performance. The study provides initial evidence for the mediating role of firm capabilities in the association between entrepreneurial competencies and firm performance.
Assessment of Social Accountability through SDGs of Corporate Sector during COVID-19 in India

The major focus in the field of sustainability assessment for the past few years is on analysing the sustainability practices of corporates on an annual basis. Less attention has been devoted to estimating the sustainability practices on an event basis. The current study was carried out to analyse the sustainability practices adopted by companies during the period of Coronavirus Disease 2019 (COVID-19). A sustainability performance measurement (SPM) framework was constructed using content analysis, to measure the performance of Sensex companies towards sustainability efforts. Sensex constitutes 30 well-established and financially sound companies listed in the Bombay Stock Exchange (BSE). The primary elements of the SPM framework were derived from Sustainable Development Goals, which are considered to be a blueprint for a sustainable future. The initiatives taken by companies during the period of ‘covidization’ were classified under different parameters of SPM and then quantified with the help of mathematical tools. The results signify that there lies a scope of 63.08% improvement in sustainability practices of overall industries. Further, there is a huge gap of 76.92% between the best-performing and least-performing companies. The performance of all the sectors studied for the sustainability practices was statistically at par with each other. However, the difference between the best-performing (fast-moving consumer goods—FMCG) and least performing (finance) sectors was found to be 42.74%. The result of analysis of variance (ANOVA) for performance across various sustainability parameters taken up by different sectors was significantly different from each other. A gap of 86.67% was uncovered in our analysis between the best-performing and least-performing sustainability parameters taken up by the companies under various sectors. Considering the fact that COVID-19 is a medical emergency, the performance of ‘good health and well-being’ as the best-performing sustainability parameter is justified. But at the same time, importance of other sustainability parameters cannot be ignored. It has also been observed that even in times of dire necessity, the prevailing undersized image of sustainability efforts of selected sample companies was not satisfactory. It is suggested that the corporate sector and the government should be more cautious in pursuing the objective of sustainability.
Production of Salvianic Acid A from l-DOPA via Biocatalytic Cascade Reactions

Salvianic acid A (SAA), as the main bioactive component of the traditional Chinese herb Salvia miltiorrhiza, has important application value in the treatment of cardiovascular diseases. In this study, a two-step bioprocess for the preparation of SAA from l-DOPA was developed. In the first step, l-DOPA was transformed to 3,4-dihydroxyphenylalanine (DHPPA) using engineered Escherichia coli cells expressing membrane-bound L-amino acid deaminase from Proteus vulgaris. After that, the unpurified DHPPA was directly converted into SAA by permeabilized recombinant E. coli cells co-expressing d-lactate dehydrogenase from Pediococcus acidilactici and formate dehydrogenase from Mycobacterium vaccae N10. Under optimized conditions, 48.3 mM of SAA could be prepared from 50 mM of l-DOPA, with a yield of 96.6%. Therefore, the bioprocess developed here was not only environmentally friendly, but also exhibited excellent production efficiency and, thus, is promising for industrial SAA production.
Serious Mental Illness Exacerbation Post-Bereavement: A Population-Based Study of Partners and Adult Children

Purpose The death of a close family member is commonly accompanied by intense grief, stress, and loss of social support. We hypothesized that recent bereavement would be associated with an increase in symptom exacerbations among adults with serious mental illness (SMI) whose partners or parents had died. Patients and Methods Adults whose partners and parents had died in Denmark between January 1, 2010, and June 30, 2016, were identified using linked population-based registries. History of SMI was defined as having a diagnosis of schizophrenia and schizoaffective disorders, major depression, and bipolar disorder in the five years preceding their family member’s death in the Danish Psychiatric Central Research Register using International Classification of Diseases-10 codes. The odds of SMI exacerbation (ie, attempt or completion of suicide or psychiatric hospitalization) among partners and children in the first two years after death in 3-month intervals were estimated with generalized estimating equations. Results 12.8% of partners and 15.0% of adult children with a history of SMI experienced any SMI exacerbation two years after bereavement. Among bereaved partners, older age (80+ years) was associated with a lower risk of experiencing an SMI exacerbation compared with partners aged 18–49 years (ORadj=0.29, [0.18–0.45]). Partners with a history of SMI had significantly increased odds of SMI exacerbations three months after their partners’ death compared to prior to their partners’ death (ORadj = 1.43, [1.13–1.81]). There was no evidence that adult children with SMI experience increased SMI exacerbations after the death of their parents compared to prior to death. Conclusion Adults with a history of SMI whose partners had died are at increased risk for an SMI exacerbation post bereavement. Additional bereavement resources and support should be provided to those with a history of SMI, especially in the period immediately after death.
Developing a Multimodal HMI Design Framework for Automotive Wellness in Autonomous Vehicles

With the development of autonomous technology, the research into multimodal human-machine interaction (HMI) for autonomous vehicles (AVs) has attracted extensive attention, especially in automotive wellness. To support the design of HMIs for automotive wellness in AVs, this paper proposes a multimodal design framework. First, three elements of the framework were envisioned based on the typical composition of an interactive system. Second, a five-step process for utilizing the proposed framework was suggested. Third, the framework was applied in a design education course for exemplification. Finally, the AttrakDiff questionnaire was used to evaluate these interactive prototypes with 20 participants who had an affinity for HMI design. The questionnaire responses showed that the overall impression was positive and this framework can help design students to effectively identify research gaps and expand design concepts in a systematic way. The proposed framework offers a design approach for the development of multimodal HMIs for autonomous wellness in AVs.
Cost-Effectiveness Analysis of the Oncotype DX Breast Recurrence Score® Test in Node-Negative Early Breast Cancer

Background The 21-gene assay (the Oncotype DX Breast Recurrence Score® test) is a validated multigene assay which produces the Recurrence Score® result (RS) to inform decisions on the use of adjuvant chemotherapy in human epidermal growth factor receptor 2-negative (HER2-), hormone receptor positive (HR+) early invasive breast cancer. A model-based economic evaluation estimated the cost-effectiveness of the 21-gene assay against the use of clinical risk tools alone based on the latest evidence from prospective studies. Methods The proportion of patients assigned to chemotherapy conditional on their RS result was obtained from retrospective data from the Clalit registry. The probability of distant recurrence with endocrine and chemo-endocrine therapy conditional on RS result was obtained from TAILORx and NSABP B-20 trials. The cost-effectiveness of the 21-gene assay compared to using clinical risk tools alone was estimated in terms of cost per quality-adjusted life-year (QALY) over a lifetime horizon. Results The 21-gene assay was more effective (0.17 more quality-adjusted life years) at a lower cost (-£519) over a lifetime compared to clinical risk alone. The model results were sensitive to assumptions around the magnitude of benefit of chemotherapy in the high RS result subgroup. Other assumptions underpinning the model, such as the proportion of patients assigned to chemotherapy in the low and mid-range RS result subgroups and long-term distant recurrence probabilities, had a smaller impact on the results. Conclusion The analysis showed that the cost-effectiveness of the 21-gene assay is sensitive to assumptions for chemotherapy sparing for patients with RS 0–25 whose outcomes with endocrine therapy are no worse compared to chemotherapy-assigned patients, and a chemotherapy benefit in the RS 26–100 group. Future studies need to incorporate a wider set of tumour profiling tests other than the 21-gene assay to allow a direct comparison of their cost-effectiveness.
Teachers’ Health: How General, Mental and Functional Health Indicators Compare to Other Employees? A Large French Population-Based Study

Teachers’ health is a key factor of any successful education system, but available data are conflicting. To evaluate to what extent teachers’ health could be at risk, we used pre-pandemic data from the CONSTANCES population-based French cohort (inclusion phase: 2012–2019) and compared teachers (n = 12,839) included in the cohort with a random subsample selected among all other employees (n = 32,837) on four self-reported health indicators: perceived general health, depressive symptoms (CES-D scale), functional limitations in the last six months, and persistent neck/back troubles (Nordic questionnaire). We further restricted our comparison group to the State employees (n = 3583), who share more occupational similarities with teachers. Lastly, we focused on teachers and evaluated how their health status might differ across teaching levels (primary, secondary, and higher education). As compared to non-teacher employees, and even after adjusting for important demographic, socioeconomic, lifestyle, and occupational confounders, teachers were less likely to report bad perceived health and depressive symptoms but were more likely to present functional limitations. Trends were similar in the analyses restricted to State employees. Within the teaching population, secondary school teachers were more likely to report depressive symptoms but less frequently declared persistent neck/back troubles than primary school teachers. Our descriptive cross-sectional study based on a probability sampling procedure (secondary use of CONSTANCES inclusion data) did not support the idea that teachers’ health in France was particularly at risk in the pre-pandemic period. Both cross-cultural and longitudinal studies are needed to further gain information on the topic of teachers’ health around the world and to monitor its evolution over time, particularly during crises impacting the education system such as the COVID-19 pandemic.
Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies

Cancer immunotherapy has fundamentally altered cancer treatment; however, its efficacy is limited to a subset of patients in most clinical settings. The immune system plays a key role in cancer progression from tumor initiation to the metastatic state. Throughout the treatment course, communications between the immune cells in the tumor microenvironment and the immune macroenvironment, as well as interactions between the immune system and cancer cells, are dynamic and constantly evolving. To improve the clinical benefit for patients who do not respond completely to immunotherapy, the molecular mechanisms of resistance to immunotherapy must be elucidated in order to develop effective strategies to overcome resistance. In an attempt to improve and update the current understanding of the molecular mechanisms that hinder immunotherapy, we discuss the molecular mechanisms of cancer resistance to immunotherapy and the available treatment strategies.
Flow‐recruitment relationships for Shoal Chub (
 Macrhybopsis hyostoma
 ) and implications for managing environmental flows

Regulation of river flow regimes by dams and diversions impacts aquatic biota and ecosystems globally. However, our understanding of the ecological consequences of flow alteration and ecological benefits of flow restoration lags behind our ability to manipulate flows, and there is a need for broader development of flow-ecology relationships. Approaches for establishing flow-ecology relationships have recently shifted away from state-based methods that analyze snapshots of ecological conditions and towards rate-based methods focused on mechanisms that link hydrology with dynamics of important ecological components and processes. We used a rate-based approach to validate environmental flow standards developed for the lower Brazos River, Texas, by analyzing the relationship between flow regime components and recruitment strength of imperiled Shoal Chub ( Macrhybopsis hyostoma ), a fluvial specialist and pelagic-broadcast spawning fish. We collected 254 age-0 Shoal Chub (9 − 40 mm total length), extracted their otoliths to estimate age in days, and used a generalized additive model to regress the number of captured recruits that hatched on a calendar date against flow regime metrics such as pulse magnitude, flow rate of change, and pulse timing in relation to environmental flow standards proposed by a science advisory committee (Brazos River Basin and Bay Area Expert Science Team). The model revealed flow magnitude, rate of change, and timing were all significant predictors that collectively explained 60% of variation in the recruitment strength index. Hindcasting for 1919 − 2020 showed a general reduction in recruitment strength following commencement of flow regulation in the lower Brazos River and revealed that high recruitment correlated with years in which most or all proposed flow tiers were attained, whereas low recruitment correlated with years when less than half of the targeted tiers were attained. Our
The missing link in biogeographic reconstruction: Accounting for lineage extinction rewrites history

In the most widely used family of methods for ancestral range estimation (ARE), dispersal, speciation and extirpation events are estimated from information on extant lineages. However, this approach fails to consider the geographic distribution of extinct species and their position on the phylogenetic tree, an omission that could compromise reconstruction. Here, we present a method that models the geographic distribution of extinct species and we quantify the potential inaccuracy in ancestral range estimation when extinction rates are above zero.
Discovering the Expanding Universe

Acknowledgments Foreword 1. Introduction 2. Cosmological concepts at the end of the Middle Ages 3. Nebulae as a new astronomical phenomenon 4. On the construction of the Heavens 5. Island universes turn into astronomical facts: a universe of galaxies 6. The early cosmology of Einstein and de Sitter 7. The dynamical universe of Friedmann 8. Redshifts: how to reconcile Slipher and de Sitter? 9. Lemaitre discovers the expanding universe 10. Hubble's contribution of 1929 11. The breakthrough for the expanding universe 12. Hubble's anger about de Sitter 13. Robertson and Tolman join the game 14. The Einstein-de Sitter universe 15. Are Sun and Earth older than the universe? 16. In search of alternative tracks 17. The seed for the Big Bang 18. Summary and postscript Appendix References Index.
How to Increase the Attractiveness of the Public Health Service in Germany as a Prospective Employer? Part II of the OeGD-Studisurvey

The Public Health Service (PHS) in Germany has had difficulties in recruiting enough qualified staff for years, but there is limited research on what factors drive decisions to (not) join the PHS workforce. We explored reasons for this perceived (lack of) attractiveness. We conducted two cross-sectional surveys among medical students (MS), public health students and students from other PHS-relevant fields (PH&ONM) in Germany before (2019/2020) and during the COVID-19 pandemic (2021). Both waves surveyed self-reported reasons for why students did (not) consider working in the PHS as attractive and how this could be improved, using open-question items. Qualitative and quantitative content analyses were conducted according to Mayring. In total, 948 MS and 445 PH&ONM provided valid written responses. Reasons for considering the PHS as attractive were, among others, the perception of a good work-life balance, high impact, population health focus, and generally interesting occupations. Suggestions to increase attractiveness included reducing bureaucracy, modernization/digitalization, and more acknowledgement of non-medical professionals. Among MS, reasons against were too little clinical/patient-related activities, low salary, and occupations regarded as boring. Our findings indicate areas for improvement for image, working conditions in, and institutional structures of the PHS in Germany to increase its attractiveness as an employer among young professionals.
Establishing the Nexus Between Iron Status and Markers of Immune Functions Among School Age Children in Ogun State, Nigeria

Iron deficiency as a public health problem is based on the seriousness of its consequences on human health suggesting that certain indices of iron status are associated with anthropometric measures which are used independently as markers of immune functions. This study established the relationship between the iron status, and markers of immune functions among school age children in selected Local Government Areas (LGAs) of Ogun state. A multistage sampling technique was used to select three hundred and twelve school age children from the three senatorial districts of Ogun State, Nigeria. A pre-tested and structured questionnaire was used to obtain information on socio-economic characteristics as well as information on Water, Sanitation and Hygiene (WASH) among the respondents. Blood samples of the children were analyzed for biochemical [serum ferritin (SF), C-reactive protein (CRP), Heamoglobin (Hb), reticulocyte count] parameters. Selected immune function markers [CD4, white blood cell differentials (Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils)] and parasitic infections (stool examination and Malaria screening) were also measured using standard procedures. Data were analyzed using frequency counts, percentages, means, standard deviations, correlation, T-test and Chi-Square. Results showed that 36.5% of the respondent families earned less than two hundred thousand naira annually. Also, 43.0% and 62.0% of the mothers had secondary and tertiary education respectively. WASH practices showed that 61.1% of the respondents did not have a place for handwashing. The study further revealed that the prevalence of iron deficiency was 23.7%, aneamia was 16.3% while 13.1% of the anaemic children were due to iron deficiency aneamia with significant sector (p=0.003) and gender (p=0.032) differences. Malaria (17.6%) and helmintes (18.3%) infection also showed a significant difference in the sector (p=0.020, p=0.042). The range of CD4 counts, Neutrophils, Lymphocytes, Monocytes, Basophils and Eosinophils were 708.85 to 727.11, 3.31 to 3.88, 3.03 to 4.38, 0.53 to 0.59, 0.03 to 0.04, 0.33 to 0.38 respectively. CRP positively correlated with household size (r= 0.155), Heamoglobin(r= 0.238), serum ferittin (r= 0.101), and PCV (r= 0.103). CD4 also positively correlated with mothers age and education (r= 0.252; r= 0.142) but negatively related to PCV(r= -0.102) while malaria and Household size (r=0.109) also shows a positive relationship. This study concluded that a significant relationship exists between socio economic status, makers of iron status and infections in the children. Hence, appropriate investigations for iron status and inflammation/infection screening, need to be integral in the evaluation of anaemia, and Interventions that target the multifactorial nature of anaemia in school-aged children need to be strengthened.