bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors
Authors: Naito Yoichi , Mishima Saori , Akagi Kiwamu , Hayashi Naomi , Hirasawa Akira , Hishiki Tomoro , Igarashi Ataru , Ikeda Masafumi , Kadowaki Shigenori , Kajiyama Hiroaki , Kato Motohiro , Kenmotsu Hirotsugu , Kodera Yasuhiro , Komine Keigo , Koyama Takafumi , Maeda Osamu , Miyachi Mitsuru , Nishihara Hiroshi , Nishiyama Hiroyuki , Ohga Shouichi , Okamoto Wataru , Oki Eiji , Ono Shigeru , Sanada Masashi , Sekine Ikuo , Takano Tadao , Tao Kayoko , Terashima Keita , Tsuchihara Katsuya , Yatabe Yasushi , Yoshino Takayuki , Baba Eishi
Published: May 2023

Background

Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the ‘Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)’.

Methods

Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done.

Results

The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors.

Conclusion

The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.
Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery: a multicentre retrospective cohort series
Authors: Talboom K. , Greijdanus N. G. , Brinkman N. , Blok R. D. , Roodbeen S. X. , Ponsioen C. Y. , Tanis P. J. , Bemelman W. A. , Cunningham C. , de Lacy F. B. , Hompes Roel
Published: May 2023

Purpose

Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR.

Methods

This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up.

Results

Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008).

Conclusion

Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.
A cost-of-illness study of Behçet syndrome in Italy
Authors: Lorenzoni Valentina , Marinello Diana , Palla Ilaria , Mosca Marta , Turchetti Giuseppe , Talarico Rosaria
Published: May 2023

Objective

This study aims at evaluating the cost-of-illness (COI) of patients diagnosed with Behcet’s syndrome (BS) in Italy, trying to depict the impact of different costs’ components to the overall economic burden and analysing the variability of costs according to years since diagnosis and age at first symptoms.

Methods

With a cross-sectional evaluation, we surveyed a large sample of BS patients in Italy assessing several dimensions related to BS, also including fact related to the use of health resources utilization, formal and informal care, and productivity losses. Overall costs, direct health, direct non-health, and indirect costs were thus estimated per patient/year considering a Societal perspective and the impact of years since diagnosis, age at first symptoms on costs was evaluated using generalized linear model (GLM) and a two-part model, adjusting for age and distinguishing among employed and non-employed responders.

Results

A total of 207 patients were considered in the present study. From the perspective of the Society, mean overall costs for BS patient were estimated to be 21,624 € (0;193,617) per patient/year. Direct non-health expenses were the main costs component accounting for 58% of the overall costs, followed direct health costs, 36%, while indirect costs because of productivity losses represented 6% of the overall costs. Being employed resulted in significantly lower overall costs (p = 0.006). Results from the multivariate regression analyses suggested that the probability of incurring in overall costs equal to zero decreased as time from BS diagnosis is 1 year or more as compared to newly diagnosed patients (p < 0.001); while among those incurring in expenses, costs decreased for those experiencing first symptoms between 21 and 30 years (p = 0.027) or later (p = 0.032) as compared to those having symptoms earlier. Similar findings emerged among the subgroups of patients declaring themselves as workers, while no impact of years since diagnosis or age of first symptoms was found among non-workers.

Conclusions

The present study offers a comprehensive overview of the economic consequences imposed by BS in a societal perspective, providing insights into the distribution of the different costs component related to BS, thus helping the development of targeted policies.
Strong convergence of an adaptive time-stepping Milstein method for SDEs with monotone coefficients
Authors: Kelly Cónall , Lord Gabriel J. , Sun Fandi
Published: May 2023

We introduce an explicit adaptive Milstein method for stochastic differential equations with no commutativity condition. The drift and diffusion are separately locally Lipschitz and together satisfy a monotone condition. This method relies on a class of path-bounded time-stepping strategies which work by reducing the stepsize as solutions approach the boundary of a sphere, invoking a backstop method in the event that the timestep becomes too small. We prove that such schemes are strongly$$L_2$$L2convergent of order one. This order is inherited by an explicit adaptive Euler–Maruyama scheme in the additive noise case. Moreover we show that the probability of using the backstop method at any step can be made arbitrarily small. We compare our method to other fixed-step Milstein variants on a range of test problems.
Monte Carlo integration of $$C^r$$ functions with adaptive variance reduction: an asymptotic analysis
Authors: Plaskota Leszek , Przybyłowicz Paweł , Stȩpień Łukasz
Published: May 2023

The theme of the present paper is numerical integration of $$C^r$$

C
r

functions using randomized methods. We consider variance reduction methods that consist in two steps. First the initial interval is partitioned into subintervals and the integrand is approximated by a piecewise polynomial interpolant that is based on the obtained partition. Then a randomized approximation is applied on the difference of the integrand and its interpolant. The final approximation of the integral is the sum of both. The optimal convergence rate is already achieved by uniform (nonadaptive) partition plus the crude Monte Carlo; however, special adaptive techniques can substantially lower the asymptotic factor depending on the integrand. The improvement can be huge in comparison to the nonadaptive method, especially for functions with rapidly varying rth derivatives, which has serious implications for practical computations. In addition, the proposed adaptive methods are easily implementable and can be well used for automatic integration.
If the party is good, you can stay longer—effects of trait hedonic capacity on hedonic quantity and performance
Authors: Bernecker Katharina , Becker Daniela , Guobyte Aiste
Published: May 2023

Research suggests that people’s capacity to successfully pursue hedonic goals is at least as important for well-being as trait self-control. Extending this research, we tested whether trait hedonic capacity is related to more time spent with hedonic goal pursuit (i.e., hedonic quantity) and whether this explains its positive relationship with well-being. Second, we explored whether this may come at a cost for people’s performance. Results show that people with higher trait hedonic capacity do spend more time with hedonic goal pursuit (Study 1 and 2). However, hedonic quality not hedonic quantity accounts for its positive relationship with well-being. Further, people higher vs. lower in trait hedonic capacity perform equally well in their studies (Study 2) and their jobs (Study 3 and 4). Thus, trait hedonic capacity seems to allow people to invest more time into their hedonic goals in a way that does not jeopardize their academic and job performance.
Cardiometabolic risk in people under 40 years with severe mental illness: reading between the guidelines
Authors: Carolan Aoife , Hynes Caroline , McWilliams Stephen , Ryan Cristín , Strawbridge Judith , Keating Dolores
Published: May 2023

People with severe mental illness (SMI) have a shorter life expectancy than the rest of the population. Multimorbidity and poorer physical health contribute to this health inequality. Cardiometabolic multimorbidity confers a significant mortality risk in this population. Multimorbidity is not restricted to older people and people with SMI present with multimorbidity earlier in life. Despite this, most screening, prevention and treatment strategies target older people. People under 40 years with SMI are underserved by current guidelines for cardiovascular risk assessment and reduction. Research is needed to develop and implement interventions to reduce cardiometabolic risk in this population.
Purinergic P2X3 receptors in the carotid body as new therapeutic targets for controlling heart failure
Authors: He Ximeng , Zhou Zhichao
Published: May 2023

Heart failure is associated with multiple mechanisms, including sympatho-excitation, and is one of the leading causes of death worldwide. Enhanced carotid body chemoreflex function is strongly related to excessive sympathetic nerve activity and sleep-disordered breathing in heart failure. How to reduce the excitability of the carotid body is still scientifically challenging. Both clinical and experimental evidence have suggested that targeting purinergic receptors is of great potential to combat heart failure. In a recent study, Lataro et al. (Lataro et al. in Nat Commun 14:1725, 5) demonstrated that targeting purinergic P2X3 receptors in the carotid body attenuates the progression of heart failure. Using a series of molecular, biochemical, and functional assays, the authors observed that the carotid body generates spontaneous, episodic burst discharges coincident with the onset of disordered breathing in male rats with heart failure, which was generated by ligating the left anterior descending coronary artery. Moreover, P2X3 receptor expression was found to be upregulated in the petrosal ganglion chemoreceptive neurons of rats with heart failure. Of particular note, treatment with a P2X3 antagonist rescued pathological breathing disturbances, abolished episodic discharges, reinstated autonomic balance, attenuated cardiac dysfunction, and reduced the immune cell response and plasma cytokine levels in those rats.
Diagnosis and management of osteoporosis in Saudi Arabia: 2023 key updates from the Saudi Osteoporosis Society
Authors: Al-Saleh Yousef , Sulimani Riad , Sabico Shaun , Alshahrani Fahad M. , Fouda Mona A. , Almohaya Mohammed , Alaidarous Salwa B. , Alkhawashki Hazem M. , Alshaker Mohammed , Alrayes Hanan , Saleh Najla , Al-Daghri Nasser M.
Published: May 2023

Summary

The Saudi Osteoporosis Society (SOS) has updated its guidelines for the diagnosis and management of osteoporosis in Saudi Arabia (SA), with emphasis on postmenopausal women. This document is relevant to all healthcare professionals in SA involved in the care of patients with osteoporosis and osteoporosis-related fractures.

Introduction

The SOS launched the first national osteoporosis guidelines in 2015 and spearheaded the Gulf Cooperation Council Countries (GCC) osteoporosis consensus report in 2020 which was under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO). This paper highlights a major update of the guidelines in the SA setting.

Methods

This guideline is an adaptation of the current guidelines derived from ESCEO, the American Association of Clinical Endocrinologists (AACE), and the GCC osteoporosis consensus report and studies on osteoporosis done in SA. Where accessible, the timeliest systematic review, meta-analysis, and randomized controlled trials were used as evidence.

Results

The present update includes new recommendations for the assessment of osteoporosis taking into consideration the Saudi model of FRAX for fracture probabilities, appropriate doses for the maintenance of vitamin D status and calcium, the use of representative blood analytes for therapy monitoring, the use of romosozumab and sequential therapy in the pharmacological management strategies, and the establishment of fracture liaison services to prevent secondary fractures.

Conclusion

This updated guideline is for all healthcare professionals involved in osteoporosis and post-fracture care and management in SA and harmonized the most up-to-date changes in the field based on evidence-based medicine for use in the local setting.
Relationship between leptin and white blood cells: a potential role in infection susceptibility and severity—the Olivetti Heart Study
Authors: D’Elia Lanfranco , Masulli Maria , Iacone Roberto , Russo Ornella , Strazzullo Pasquale , Galletti Ferruccio
Published: May 2023

A number of evidence showed an emerging role of leptin on immune system, involving inflammation, and innate and adaptive immunity. Few observational studies have evaluated the relationship between leptin and immunity, albeit with low statistical power and methodological differences. Therefore, the aim of this study was to evaluate the potential role of leptin on the immunity, expressed as white blood cells (WBC)—and its subpopulations, by comprehensive multivariate models in a sample of adult men. A cross-sectional evaluation of a general population comprised 939 subjects participating in the Olivetti Heart Study, with available leptin levels and WBC—and its subpopulations. WBC were significantly and positively associated with leptin, C-reactive protein and HOMA index (p < 0.05), but not with age and anthropometric indices (p > 0.05). The multivariate analysis confirmed the association between leptin and WBC, after accounting for main confounders (p < 0.05). Additional analysis on WBC subpopulations showed a positive and significant correlation between leptin and lymphocytes, monocytes and eosinophils (p < 0.05), but not with neutrophils and basophils (p > 0.05). After stratification by body weight, the positive and significant association between leptin and WBC—and its subpopulations—was found in excess body weight participants. The results of this study indicate a direct relationship between leptin levels and WBC—and its subpopulations—in excess body weight participants. These results support the hypothesis that leptin has modulatory functions on immunity and role in the pathophysiology of immune-related diseases, in particular in those associated with excess body weight.
Temporal trends of particle gross β-activity and PM2.5 mass concentrations in the USA during 2001–2017
Authors: Matthaios Vasileios N. , Wolfson Jack M. , Li Longxiang , Lawrence Joy , Koutrakis Petros
Published: May 2023

Recent studies conducted in the USA have shown that adverse health effects of fine particulate matter (PM2.5) persist at levels below the national air quality standards. More recently, particle radioactivity has also been associated with adverse health effects. However, the importance of particle radioactivity at low PM2.5 levels has not been thoroughly explored. The present paper investigates the temporal trends and the relationship of particle gross β-activity (PM-β) and PM2.5 mass in the 48 states of the contiguous USA during the period of 2001–2017. With the implementation of stringent air pollution control policies, national ambient PM2.5 concentrations decreased by 38.5% during this period. However, a smaller decrease of 9.4% was observed for PM-β, while the mean PM-β/PM2.5 ratio increased by 49.1%. PM-β is mostly associated with radon emissions and its progeny, which do not change much with time. The largest PM2.5 and PM-β reductions were observed in the Southeast, while the smallest were found in the West. When the aggregated PM-β to PM2.5 ratio is stratified by PM2.5 levels, the ratio was found to be highest when PM2.5 is <3 μg/m3, with a median PM-β to PM2.5 ratio of 0.77 (0.64–0.88; 25th–75th percentiles). Overall, when not stratified by PM2.5 levels, the greatest state-wide overall PM-β /PM2.5 ratios were found in Wyoming (0.69) and South Dakota (0.51), areas with higher radon, while the lowest (0.17) were in Delaware followed by New Jersey (0.18). These results indicate that the ratio of ambient particle radioactivity to particle mass concentration typically is higher at low PM2.5 levels, and consequently, the toxicity per unit mass is expected to be higher.
Alexithymia and Hypertension: Does Personality Matter? A Systematic Review and Meta-analysis
Authors: Di Tella Marialaura , Benfante Agata , Airale Lorenzo , Castelli Lorys , Milan Alberto
Published: May 2023

Purpose of review

Personality characteristics, such as alexithymia, may lead to alterations in the autonomic nervous system functionality, predisposing individuals to an increased risk of hypertension (HTN). The present meta-analysis aimed to quantify the presence of alexithymia in people with HTN and to assess for potential sources of heterogeneity between studies. PubMed, PsycINFO and Scopus databases were systematically searched, using the following strings: (“alexithymia” OR “alexithymic”) AND (“hypertension” OR “hypertensive”). Data were meta-analyzed with random-effects models.

Recent findings

A total of 13 studies met the inclusion criteria. The prevalence of alexithymia in people with and without HTN were obtained from 5 studies (26.3% vs 15.0%; pooling of odd ratios, 3.15 [95% CI, 1.14;8.74]), whereas the mean level of alexithymia between people with and without HTN was obtained from 7 studies Hedges g, 1.39 [95% CI, -0.39;3.16]). There was a significant association between alexithymia prevalence and year of article publication (ĝ = -0.04; 95% CI, -0.07;-0.01), whereas no significant relationship was detected between the former and both sex and age.

Findings revealed a greater prevalence of alexithymia in people with HTN than in participants without HTN. These findings suggest that alexithymia may contribute to both the onset and persistence of HTN symptomatology. However, future research is needed to clarify this association.
ECMO as a bridge to cardiac surgery: stabilizing unstable patients for a definitive procedure
Authors: Raman Jai , Saxena Pankaj , Dobrilovic Nikola
Published: May 2023

Introduction

Extracorporeal membrane oxygenation (ECMO) in adults has been used in post-cardiotomy patients who decline hemodynamically. Cardiogenic shock in patients with potential surgically correctable cardiac conditions are at significantly higher risk for post-operative morbidity and mortality. We present experience with a pre-emptive approach of ECMO institution pre-operatively to stabilize patients with cardiogenic shock.

Materials and methods

This study expands on a pilot study with a group of twenty patients who were supported with ECMO pre-operatively in different institutions over a period between 2011 and 2021. The patients presented with cardiogenic shock. Peripheral veno-arterial (VA) ECMO support was used in all the patients. Cardiac surgery was performed via median sternotomy utilizing the in situ ECMO cannulae to institute cardiopulmonary bypass (CPB).

Results

Seventeen patients were weaned off ECMO support following a mean duration of support of 156 h. Fifteen patients survived to discharge. The 30-day mortality and in-hospital mortality were 25% (expected 67% by European System for Cardiac Operative Risk Evaluation (EuroSCORE) II). The causes of mortality included persistent bleeding in 2 patients due to liver dysfunction, and one with low platelet counts. The other two had multi-organ failure.

Conclusions

Variable period of pre-operative ECMO support provides hemodynamic stability and may prevent or reverse the multi-organ dysfunction if instituted on time in patients presenting with cardiogenic shock. This strategy allows cardiac surgery to be performed with acceptable risk.
High glucose-induced IL-7/IL-7R upregulation of dermal fibroblasts inhibits angiogenesis in a paracrine way in delayed diabetic wound healing
Authors: Gao Ruikang , Zhou Peng , Li YiQing , Li Qin
Published: May 2023

It is widely acknowledged that diabetes leads to slow wound healing and ulceration, and severe serious diabetic foot ulceration may result in amputation. In recent years, much emphasis has been placed on exploring diabetic wound healing to protect patients from adverse events. We recently found interleukin-7 (IL-7), a growth factor for B-cells and T-cells, and its receptor was significantly upregulated in high glucose-induced fibroblasts and skin of diabetic mice. Moreover, IL-7 stimulated fibroblasts secreted ANGPTL4, which inhibited angiogenesis of endothelial cells resulting in delayed wound healing. In our previous study, fibroblasts, endothelial cells and keratinocytes were exposed to normal glucose (5.5 mM) or high glucose (30 mM) medium for 24 h, and RNA sequencing showed that IL-7 and IL-7R were significantly upregulated in fibroblasts. To remove the effect of high glucose and explore the influence of IL-7, exogenous rMuIL-7 used to treat normal mice led to delayed wound healing by inhibiting angiogenesis. Vitro experiments revealed that IL-7-induced fibroblasts inhibited endothelial cell proliferation, migration and angiogenesis. Further experiments showed that fibroblast angiopoietin-like-4 (ANGPTL4) secretion exhibited the inhibitory effect which was blocked by culture with the corresponding neutralizing antibody. Overall, our study revealed signaling pathways associated with diabetic wound healing and provided the foothold for further studies on delayed wound healing in this patient population.

Graphical abstract

Mechanism that high glucose activates IL-7-IL-7R-ANGPTL4 signal pathway in delayed wound healing. High glucose upregulates IL-7 and IL-7R in dermal fibroblasts. IL-7 stimulates dermal fibroblasts secreting Angptl4 which inhibits proliferation, migration and angiogenesis of endothelial cells in a paracrine way.
Multilateral Development Banks as Agents of Connectivity: the Asian Development Bank (ADB) and the Asian Infrastructure Investment Bank (AIIB)
Authors: Creutz Katja
Published: May 2023

The article explores connectivity from the prism of multilateral development banks. It recognises that theorising on connectivity is increasing, but as connectivity agency is less addressed, it aims to contribute to discussions on who the agents of connectivity are and how they contribute thereto. By analysing the Asian Development Bank (ADB) and the Asian Infrastructure Bank (AIIB) respectively, the article sets forth a three-dimensional agency: strategic, developmental and financial. This is in line with the multi-layered nature of the banks, which reflects the broader member states and key state interests. Next to their role as banks, they contribute to the understanding of development, in addition to which they represent key shareholder interests. The banks are both to be seen as nodes of connectivity and as active agents in realising connectivity for others.
Higher moment connectedness of cryptocurrencies: a time-frequency approach
Authors: Nyakurukwa Kingstone , Seetharam Yudhvir
Published: May 2023

The purpose of the study is to examine higher moment connectedness among 12 cryptocurrencies using data sampled at the 1-minute high-frequency interval. We use methods that demonstrate the heterogeneity of agents from their distinct investing horizons. This includes wavelet multiple cross-correlations, CEEMDAN-based Diebold-Yilmaz (DY) connectedness index and the Barunik-Krehlik (BK) frequency connectedness index. First, our results show that higher moment multiple correlations among the sampled cryptocurrencies are higher at all time scales and the relationship strengthens at lower frequencies. Second, the wavelet cross-correlations show different cryptocurrencies with the potential to lead and lag in the transmission of higher moment shocks to the whole system at different frequencies. Again, the multiple wavelet cross-correlations increase with increasing time scales. The results from the CEEMDAN-based DY connectedness index as well as the BK framework also reveal cyclical connectedness and differences in connectedness across different frequencies. The results show more connectedness of higher moments than the connectedness empirically reported for returns and volatility. Cryptocurrency connectedness has mostly been examined using the first two moments. We extend this line of literature by examining the third and fourth moments, which might be more useful for risk management purposes.
Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR + , HER2- metastatic breast cancer patients in Japan
Authors: Nozawa K. , Terada M. , Onishi M. , Ozaki Y. , Takano T. , Fakhouri W. , Novick D. , Haro J. M. , Faris L. H. , Kawaguchi T. , Tanizawa Y. , Tsurutani Junji
Published: May 2023

Introduction

This study described, in routine clinical practice in Japan, the patient characteristics, treatment patterns, and outcomes of female patients with HR + /HER2- metastatic breast cancer (MBC) who started abemaciclib treatment.

Methods

Clinical charts were reviewed for patients starting abemaciclib in 12/2018–08/2021 with a minimum of 3 months follow-up data post-abemaciclib initiation regardless of abemaciclib discontinuation. Patient characteristics, treatment patterns, and tumor response were descriptively summarized. Kaplan–Meier curves estimated progression-free survival (PFS).

Results

200 patients from 14 institutions were included. At abemaciclib initiation, median age was 59 years, and the Eastern Cooperative Oncology Group performance status score was 0/1/2 for 102/68/5 patients (58.3/38.9/2.9%), respectively. Most had an abemaciclib starting dose of 150 mg (92.5%). The percentage of patients receiving abemaciclib as 1st, 2nd, or 3rd line treatment was 31.5%, 25.8%, and 25.2%, respectively. The most frequent endocrine therapy drugs used with abemaciclib were fulvestrant (59%) and aromatase inhibitors (40%). Evaluation of tumor response was available for 171 patients, 30.4% of whom had complete/partial response. Median PFS was 13.0 months (95% CI 10.1–15.8 months).

Conclusions

In a routine clinical practice setting in Japan, patients with HR + , HER2- MBC appear to benefit from abemaciclib treatment in terms of treatment response and median PFS, with the results broadly reflecting the evidence demonstrated in clinical trials.
IT Professionals in the Gig Economy
Authors: Gussek Lisa , Wiesche Manuel
Published: May 2023

When IT work is performed through digital labor markets, IT professionals have a high degree of personal responsibility for their careers and must use appropriate strategies to be successful. This paper investigates the success of IT freelancers on digital labor platforms. Drawing on signaling theory, a dataset of 7166 IT freelancers is used to examine how activating, pointing, and supporting signals lead to success. Analysis was carried out using negative binomial regression. The results indicate that the three signaling types positively influence the objective career success of IT freelancers. This paper contributes to the literature by testing signaling theory in the new context of digital labor platforms, investigating IT specifics, and proposing support as a new type of signal for IT professionals on digital labor platforms. In practice, the results provide guidelines for IT freelancers to improve their success within their careers.
Underexplored reciprocity between genome-wide methylation status and long non-coding RNA expression reflected in breast cancer research: potential impacts for the disease management in the framework of 3P medicine
Authors: Kapinova Andrea , Mazurakova Alena , Halasova Erika , Dankova Zuzana , Büsselberg Dietrich , Costigliola Vincenzo , Golubnitschaja Olga , Kubatka Peter
Published: May 2023

Breast cancer (BC) is the most common female malignancy reaching a pandemic scale worldwide. A comprehensive interplay between genetic alterations and shifted epigenetic regions synergistically leads to disease development and progression into metastatic BC. DNA and histones methylations, as the most studied epigenetic modifications, represent frequent and early events in the process of carcinogenesis. To this end, long non-coding RNAs (lncRNAs) are recognized as potent epigenetic modulators in pathomechanisms of BC by contributing to the regulation of DNA, RNA, and histones’ methylation. In turn, the methylation status of DNA, RNA, and histones can affect the level of lncRNAs expression demonstrating the reciprocity of mechanisms involved. Furthermore, lncRNAs might undergo methylation in response to actual medical conditions such as tumor development and treated malignancies. The reciprocity between genome-wide methylation status and long non-coding RNA expression levels in BC remains largely unexplored. Since the bio/medical research in the area is, per evidence, strongly fragmented, the relevance of this reciprocity for BC development and progression has not yet been systematically analyzed. Contextually, the article aims at:

consolidating the accumulated knowledge on both—the genome-wide methylation status and corresponding lncRNA expression patterns in BC and

highlighting the potential benefits of this consolidated multi-professional approach for advanced BC management.

Based on a big data analysis and machine learning for individualized data interpretation, the proposed approach demonstrates a great potential to promote predictive diagnostics and targeted prevention in the cost-effective primary healthcare (sub-optimal health conditions and protection against the health-to-disease transition) as well as advanced treatment algorithms tailored to the individualized patient profiles in secondary BC care (effective protection against metastatic disease). Clinically relevant examples are provided, including mitochondrial health control and epigenetic regulatory mechanisms involved.
Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine
Authors: Lučanský Vincent , Holubeková Veronika , Kolková Zuzana , Halašová Erika , Samec Marek , Golubnitschaja Olga
Published: May 2023

Since 2009, the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Brussels) promotes the paradigm change from reactive approach to predictive, preventive, and personalized medicine (PPPM/3PM) to protect individuals in sub-optimal health conditions from the health-to-disease transition, to increase life-quality of the affected patient cohorts improving, therefore, ethical standards and cost-efficacy of healthcare to great benefits of the society at large. The gene-editing technology utilizing CRISPR/Cas gene-editing approach has demonstrated its enormous value as a powerful tool in a broad spectrum of bio/medical research areas. Further, CRISPR/Cas gene-editing system is considered applicable to primary and secondary healthcare, in order to prevent disease spread and to treat clinically manifested disorders, involving diagnostics of SARS-Cov-2 infection and experimental treatment of COVID-19. Although the principle of the proposed gene editing is simple and elegant, there are a lot of technological challenges and ethical considerations to be solved prior to its broadly scaled clinical implementation. This article highlights technological innovation beyond the state of the art, exemplifies current achievements, discusses unsolved technological and ethical problems, and provides clinically relevant outlook in the framework of 3PM.
Evaluation of SEBS and SEBAL algorithms for estimating wheat evapotranspiration (case study: central areas of Khuzestan province)
Authors: Zoratipour Elahe , Mohammadi Amir Soltani , Zoratipour Amin
Published: May 2023

This study aimed to accurately estimate daily wheat evapotranspiration using two remote sensing algorithms, Surface Energy Balance System (SEBS) and Surface Energy Balance Algorithm for Land (SEBAL), in central Khuzestan province during 2019–2020. The results of two algorithms were compared with lysimeter (as a direct method), FAO-Penman–Monteith (FAO-PM), two temperature-based methods (Hargreaves-Samani and Blaney-Criddle), two radiation-based methods (Priestley–Taylor and Doorenbos–Pruitt), and two mass transfer-based methods (Mahringer and World Meteorology Organization) (as indirect methods). Coefficient of Determination (R2), Root-Mean-Square Error (RMSE), Percentage of Bias (PBIAS), Mean Bias Error, Mean Absolute Percentage Error, and Nash–Sutcliffe indicators used for comparing the results. According to the results, both SEBAL and SEBS algorithms showed the highest compatibility with lysimeter data (R2 = 0.92 and 0.96, RMSE = 2.15 and 1.53 mm/day, respectively). Comparing both algorithms with the FAO-PM method, resulted in RMSE and R2 of 2.42 mm/day and 0.87 for SEBS and 3.14 mm/day and 0.79 for SEBAL. The Hargreaves-Samani method (R2 = 0.72, RMSE = 16.4 mm/day) and (R2 = 0.8, RMSE = 10.4 mm/day) among temperature-based methods, Doorenbos–Pruitt (R2 = 0.71, RMSE = 3.33 mm/day) and (R2 = 0.79, RMSE = 2.63 mm/day) among radiation-based methods, and the Mahringer method (R2 = 0.6, RMSE = 6.8 mm/day mm/day) and (R2 = 0.68, RMSE = 5.51 mm/day) among mass transfer-based methods yielded better estimations than SEBAL and SEBS algorithms, respectively. Owing to the high accuracy of SEBAL and SEBS algorithms, in estimating the amount of evapotranspiration in the study area and close to the actual values in the field, using energy balance algorithms is recommended in Khuzestan province.
Advanced Organotypic In Vitro Model Systems for Host–Microbial Coculture
Authors: Kim Raehyun
Published: May 2023

In vitro model systems have been advanced to recapitulate important physiological features of the target organ in vivo more closely than the conventional cell line cultures on a petri dish. The advanced organotypic model systems can be used as a complementary or alternative tool for various testing and screening. Numerous data from germ-free animal studies and genome sequencings of clinical samples indicate that human microbiota is an essential part of the human body, but current in vitro model systems rarely include them, which can be one of the reasons for the discrepancy in the tissue phenotypes and outcome of therapeutic intervention between in vivo and in vitro tissues. A coculture model system with appropriate microbes and host cells may have great potential to bridge the gap between the in vitro model and the in vivo counterpart. However, successfully integrating two species in one system introduces new variables to consider and poses new challenges to overcome. This review aims to provide perspectives on the important factors that should be considered for developing organotypic bacterial coculture models. Recent advances in various organotypic bacterial coculture models are highlighted. Finally, challenges and opportunities in developing organotypic microbial coculture models are also discussed.
Digital Civics and Algorithmic Citizenship in a Global Scenario
Authors: Tomasello Federico
Published: May 2023

How should the notion of civics be rethought in the digital age and within the infosphere? The commentary addresses this question by focusing on two main issues. The first part delves into the effects of the dynamics of “surveillance capitalism” and datafication processes on the possible developments of the idea of civics in the digital sphere. It stresses the need to set the issue of users’ data rights at the center of digital civic initiatives. The second part explores the notions of political community and membership that should underpin the idea of digital civics. It argues that the diverse range of values and virtues which shape civics on a global scale should be taken into consideration to define the spatial scope—or political geography—of the community to which digital civic initiatives are addressed.
Iperparatiroidismo nel contesto della MEN2A: dalla genetica alla gestione clinica
Authors: Gambale Carla , Matrone Antonio , Prete Alessandro , Romei Cristina , Elisei Rossella
Published: May 2023

Sommario

L’iperparatiroidismo primitivo (IPP), condizione caratterizzata da aumentata secrezione di paratormone e conseguente aumento dei valori di calcemia, può presentarsi sia in forma sporadica che familiare. Tra le forme familiari, l’IPP rappresenta una manifestazione caratteristica delle sindromi da neoplasie endocrine multiple (MEN) tipo 1, 2A e 4. Le caratteristiche cliniche dell’IPP differiscono tra diverse forme di MEN e rispetto alla forma sporadica. L’incidenza di IPP nel contesto della MEN2A varia in base al codone di RET coinvolto dalla mutazione. Nella maggioranza dei casi l’IPP è diagnosticato nel corso del follow-up dei pazienti con MEN 2A, di solito successivamente alla comparsa del carcinoma midollare della tiroide (CMT), presentandosi clinicamente in forma lieve o del tutto asintomatica. Il trattamento di scelta è l’asportazione chirurgica delle paratiroidi iperfunzionanti, accompagnata dall’esplorazione cervicale bilaterale in considerazione del potenziale coinvolgimento multighiandolare.
Popular solunar tables fail to predict fishing success in North American recreational freshwater trout fisheries
Authors: Quigley Calvin N. , Murcia Josue D. Gonzalez , Kauwe John S. K.
Published: May 2023

The solunar theory proposes that the position of the sun and moon can be used to predict activity rates in fish and game species. Several free and premium services use this theory to provide tables predicting optimal dates and times for fishing and hunting success. The efficacy of these services was tested by comparing catch per unit effort (CPUE) in a recreational freshwater trout fishery with daily solunar values and coincidence of fishing trips with peak solunar times. CPUE was also compared to environmental variables including lunar phase, lunar illumination, and wind speed. Values predicted by each of the solunar services were strongly correlated to each other and to lunar phase, however, no significant relationship was found between CPUE and any of the solunar values tested, lunar phase, or lunar illumination. Ambient air temperature showed a positive relationship with CPUE, and was a more effective predictor of fishing success than any of the solunar tables tested.
Biomass and enzymatic activities of marine bacteria in the presence of multiple metals
Authors: Bitencourt J. A. P. , Chequer L. P. T. , Waite C. C. , Oliveira G. , Oliveira A. M. S. , Pereira D. C. , Crapez M. A. C.
Published: May 2023

Marine environments are a repository for metals, and humans have enhanced this phenomenon over the years. Heavy metals are notoriously toxic due to their ability to biomagnify in the food chain and interact with cellular components. Nevertheless, some bacteria have physiological mechanisms that enable them to survive in impacted environments. This characteristic makes them important as biotechnological tools for environmental remediation. Thus, we isolated a bacterial consortium in Guanabara Bay (Brazil), a place with a long metal pollution history. To test the growth efficiency of this consortium in Cu–Zn-Pb-Ni–Cd medium, we measured the activity of key enzymes of microbial activity (esterases and dehydrogenase) under acidic (4.0) and neutral pH conditions, as well as the number of living cells, biopolymer production, and changes in microbial composition during metal exposure. Additionally, we calculated the predicted physiology based on microbial taxonomy. During the assay, a slight modification in bacterial composition was observed, with low abundance changes and little production of carbohydrates. Oceanobacilluschironomi, Halolactibacillus miurensis, and Alkaliphilus oremlandii were predominant in pH 7, despite O. chironomi and Tissierella creatinophila in pH 4, and T. creatinophila in Cu–Zn-Pb-Ni–Cd treatment. The metabolism represented by esterases and dehydrogenase enzymes suggested bacterial investment in esterases to capture nutrients and meet the energy demand in an environment with metal stress. Their metabolism potentially shifted to chemoheterotrophy and recycling nitrogenous compounds. Moreover, concomitantly, bacteria produced more lipids and proteins, suggesting extracellular polymeric substance production and growth in a metal-stressed environment. The isolated consortium showed promise for bioremediation of multimetal contamination and could be a valuable tool in future bioremediation programs.
Innovation in the 21st century: following the footsteps of Katalin Karikó
Authors: Deák Csaba , Pardi Norbert , Miklósi Ádám
Published: May 2023

Innovation is a critical component of human society, setting us apart from other animals. We possess a unique capacity to design and produce new things through cultivating a culture that values and encourages innovation. One remarkable instance of innovation in the field of biology and medicine is the mRNA vaccine platform developed by Katalin Karikó and her colleagues. In this article, we delve into the evolution of mRNA-based therapy, beginning with animal models and concluding with the first clinical trials. The history of mRNA research began with the identification of its role in protein synthesis, leading to the development of mRNA vaccine technology. Karikó's pivotal innovation was discovering the need to integrate modified nucleosides into the mRNA, decreasing its recognition by the immune system. Her story offers valuable lessons, including the importance of market demand as a booster effect, the role of emerging technologies, the significance of universities and academic institutions in fostering innovation, the role of perseverance and faith, and the role of chance.
The influence of negative travel-related experience on tourist’s brand loyalty
Authors: de Cosmo Lucrezia Maria , Piper Luigi , Mileti Antonio , Guido Gianluigi
Published: May 2023

Perceptions of negative events related to service disruptions, negative consumer associations with other brand users, or business activities not in line with consumer ethical standards can lead consumers to abandon and change a brand. Focusing on a low-cost airline company, the study analyses how negative events can affect brand loyalty by considering the mediating effect of consumers’ psychological characteristics in terms of difficulty in choosing between alternatives (choice difficulty) and tendency to switch brands (brand switcher). The paper tests two hypotheses by administering a structured questionnaire to a sample of 260 tourists and shows that: (1) brand switcher negatively mediates the relationship between negative events and brand loyalty; (2) choice difficulty positively mediates the relationship between negative events and brand loyalty. The findings carry theoretical and managerial implications and confirms the value of communication strategies in increasing brand loyalty.
Nonlinear approximation in bounded orthonormal product bases
Authors: Kämmerer Lutz , Potts Daniel , Taubert Fabian
Published: May 2023

We present a dimension-incremental algorithm for the nonlinear approximation of high-dimensional functions in an arbitrary bounded orthonormal product basis. Our goal is to detect a suitable truncation of the basis expansion of the function, where the corresponding basis support is assumed to be unknown. Our method is based on point evaluations of the considered function and adaptively builds an index set of a suitable basis support such that the approximately largest basis coefficients are still included. For this purpose, the algorithm only needs a suitable search space that contains the desired index set. Throughout the work, there are various minor modifications of the algorithm discussed as well, which may yield additional benefits in several situations. For the first time, we provide a proof of a detection guarantee for such an index set in the function approximation case under certain assumptions on the sub-methods used within our algorithm, which can be used as a foundation for similar statements in various other situations as well. Some numerical examples in different settings underline the effectiveness and accuracy of our method.
Artificial intelligence’s right to life
Authors: Milczarek Ewa
Published: May 2023

The right to life is fundamental and primary and is a precondition for exercising other rights (Ramcharan in Ramcharan (ed), The right to life in International Law, Martinus Nijhoff Publishers, Dordrecht, 1985). Its universal recognition in the arena of international law is associated with the concept of a human being endowed with inherent and inalienable dignity. Categorization of the circle of entities covered with the right to life today seems obvious and indisputable. Intense development of artificial intelligence, also the fact that it has passed the Turing test which checks AI’s thinking ability in a way similar to human reasoning, inspires a reflection on AI’s future legal status. This study will investigate a thesis of whether artificial intelligence may be entitled to the right to life. The analysis will be carried out around an exploratory question: what are the requirements for being afforded protection of the right to life?