bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROACTING: predicting pathological complete response to neoadjuvant chemotherapy in breast cancer from routine diagnostic histopathology biopsies with deep learning
Authors: Aswolinskiy Witali , Munari Enrico , Horlings Hugo M. , Mulder Lennart , Bogina Giuseppe , Sanders Joyce , Liu Yat-Hee , van den Belt-Dusebout Alexandra W. , Tessier Leslie , Balkenhol Maschenka , Stegeman Michelle , Hoven Jeffrey , Wesseling Jelle , van der Laak Jeroen , Lips Esther H. , Ciompi Francesco 
Published: November 2023

Abstract
Background
Invasive breast cancer patients are increasingly being treated with neoadjuvant chemotherapy; however, only a fraction of the patients respond to it completely. To prevent overtreatment, there is an urgent need for biomarkers to predict treatment response before administering the therapy.

Methods
In this retrospective study, we developed hypothesis-driven interpretable biomarkers based on deep learning, to predict the pathological complete response (pCR, i.e., the absence of tumor cells in the surgical resection specimens) to neoadjuvant chemotherapy solely using digital pathology H&E images of pre-treatment breast biopsies. Our approach consists of two steps: First, we use deep learning to characterize aspects of the tumor micro-environment by detecting mitoses and segmenting tissue into several morphology compartments including tumor, lymphocytes and stroma. Second, we derive computational biomarkers from the segmentation and detection output to encode slide-level relationships of components of the tumor microenvironment, such as tumor and mitoses, stroma, and tumor infiltrating lymphocytes (TILs).

Results
We developed and evaluated our method on slides from n = 721 patients from three European medical centers with triple-negative and Luminal B breast cancers and performed external independent validation on n = 126 patients from a public dataset. We report the predictive value of the investigated biomarkers for predicting pCR with areas under the receiver operating characteristic curve between 0.66 and 0.88 across the tested cohorts.

Conclusion
The proposed computational biomarkers predict pCR, but will require more evaluation and finetuning for clinical application. Our results further corroborate the potential role of deep learning to automate TILs quantification, and their predictive value in breast cancer neoadjuvant treatment planning, along with automated mitoses quantification. We made our method publicly available to extract segmentation-based biomarkers for research purposes.
Rational protein engineering of a ketoacids decarboxylase for efficient production of 1,2,4-butanetriol from arabinose
Authors: Shen Xiaolin , Xu Hongchao , Wang Tong , Zhang Ruihua , Sun Xinxiao , Yuan Qipeng , Wang Jia 
Published: November 2023

Abstract
Background
Lignocellulose, the most abundant non-edible feedstock on Earth, holds substantial potential for eco-friendly chemicals, fuels, and pharmaceuticals production. Glucose, xylose, and arabinose are primary components in lignocellulose, and their efficient conversion into high-value products is vital for economic viability. While glucose and xylose have been explored for such purpose, arabinose has been relatively overlooked.

Results
This study demonstrates a microbial platform for producing 1,2,4-butanetriol (BTO) from arabinose, a versatile compound with diverse applications in military, polymer, rubber and pharmaceutical industries. The screening of the key pathway enzyme, keto acids decarboxylase, facilitated the production of 276.7 mg/L of BTO from arabinose in Escherichia coli. Through protein engineering of the rate-limiting enzyme KivD, which involved reducing the size of the binding pocket to accommodate a smaller substrate, its activity improved threefold, resulting in an increase in the BTO titer to 475.1 mg/L. Additionally, modular optimization was employed to adjust the expression levels of pathway genes, further enhancing BTO production to 705.1 mg/L.

Conclusion
The present study showcases a promising microbial platform for sustainable BTO production from arabinose. These works widen the spectrum of potential lignocellulosic products and lays the foundation for comprehensive utilization of lignocellulosic components.
Health warning labels on heated tobacco products and their impact on use intentions and risk perceptions: a cross-sectional study of adult tobacco users in the US and Israel
Authors: Duan Zongshuan , Levine Hagai , Bar-Zeev Yael , Cui Yuxian , LoParco Cassidy R. , Wang Yan , Abroms Lorien C. , Khayat Amal , Berg Carla J. 
Published: November 2023

AbstractBackgroundHealth warning labels (HWLs) represent an evidence-based tobacco control strategy; however, their application to heated tobacco products (HTPs) and related impacts are understudied. This study examined the impact of HTP HWLs on HTP use intentions and risk perceptions among current tobacco users.MethodsWe analyzed cross-sectional survey data from adults in the US and Israel reporting past-month tobacco use and awareness of HTPs (N = 424). Multivariate analyses examined: (1) sociodemographics in relation to self-reported impact of HTP HWLs (i.e., more concerned about HTP use, reassured, no effect [referent]) among those who noticed HTP HWLs (multinomial regressions); and (2) HWL impacts in relation to HTP use intentions and perceived addictiveness and harm (linear regressions).ResultsAmong participants who noticed HTP HWLs (n = 372, 87.7%), 27.7% reported HWLs increased their concerns about HTP use, 22.6% were reassured about use, and 49.7% reported no effect. Factors associated with increased concern (vs. no effect) included other tobacco product use (aOR = 2.10, 95% CI 1.21–3.64) and being female (aOR = 1.77, 95% CI 1.03–3.05). Factors associated with being reassured about HTPs use (vs. no effect) included current HTP use (aOR = 2.11, 95% CI 1.11–4.00) and being from Israel (vs. US: aOR = 3.85, 95% CI 1.85–7.69), female (aOR = 1.91, 95% CI 1.07–3.42), and less educated (< college education: aOR = 2.57, 95% CI 1.42–4.63). Reporting that HWLs on HTPs increased concern (β = 0.46, 95% CI 0.03–0.89) and reassured of use (β = 0.94, 95% CI 0.47–1.41) were positively associated with HTP use intentions; no associations with risk perceptions were found.ConclusionsFindings indicate that most tobacco users noticed HWLs on HTPs, but the majority reported no effect or being reassured of using HTPs, effects that were magnified for specific subgroups. Both increased concern and reassurance correlated with greater use intentions. Additional research should evaluate HTP HWL impacts and ensure effectiveness in communicating risks and discouraging use.
Preoperative education in patients undergoing foot and ankle surgery: a scoping review
Authors: Vergara-Merino Laura , Lira María Jesús , Liquitay Camila Micaela Escobar , González-Kusjanovic Nicolás , Morales Sergio 
Published: November 2023

Abstract
Background
International guidelines promote preoperative education for patients undergoing orthopedic surgery. However, the evidence sustaining these recommendations comes mainly from studies for hip and knee replacement surgery. Little is known about patients undergoing foot and ankle surgery. We aimed to map and characterize all the available evidence on preoperative education for patients undergoing foot and ankle surgery.

Methods
This study complies with the PRISMA-ScR guidelines. We searched eight databases, including MEDLINE, Embase, and CENTRAL. We performed cross-citations and revised the references of included studies. We included studies addressing preoperative education in patients undergoing foot and ankle surgery. We did not exclude studies because of the way of delivering education, the agent that provided it, or the content of the preoperative education addressed in the study. Two independent authors screened the articles and extracted the data. The aggregated data are presented in descriptive tables.

Results
Of 1596 retrieved records, only 15 fulfilled the inclusion criteria. Four addressed preoperative education on patients undergoing foot and ankle surgery and the remaining 11 addressed a broader population, including patients undergoing foot and ankle surgery but did not provide separate data of them. Two studies reported that preoperative education decreases the length of stay of these patients, another reported that education increased the knowledge of the participants, and the other leaflets were well received by patients.

Conclusion
This scoping review demonstrates that evidence on preoperative education in foot and ankle surgery is scarce. The available evidence supports the implementation of preoperative education in patients undergoing foot and ankle surgery for now. The best method of education and the real impact of this education remain to be determined.
Epidemiological characteristics of seven notifiable respiratory infectious diseases in the mainland of China: an analysis of national surveillance data from 2017 to 2021
Authors: Deng Le-le , Han Ya-jun , Li Zhuo-wei , Wang Da-yan , Chen Tao , Ren Xiang , He Guang-xue 
Published: November 2023

Abstract
Background
Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017–2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies.

Methods
Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns.

Results
A total of 11,963,886 cases of the seven RIDs were reported during 2017–2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = −7.53%, P = 0.009; APC = −40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions.

Conclusions
The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses.

Graphical Abstract
Adapting and scaling a proven diabetes prevention program across 11 worksites in India: the INDIA-WORKS trial
Authors: Weber Mary Beth , Rhodes Elizabeth C. , Ranjani Harish , Jeemon Panniyammakal , Ali Mohammed K. , Hennink Monique M. , Anjana Ranjit M. , Mohan Viswanathan , Venkat Narayan K. M. , Prabhakaran Dorairaj 
Published: November 2023

Abstract
Background
Structured lifestyle change education reduces the burden of cardiometabolic diseases such as diabetes. Delivery of these programs at worksites could overcome barriers to program adoption and improve program sustainability and reach; however, tailoring to the worksite setting is essential.

Methods
The Integrating Diabetes Prevention in Workplaces (INDIA-WORKS) study tested the implementation and effectiveness of a multi-level program for reducing cardiometabolic disease risk factors at 11 large and diverse worksites across India. Herein, we describe and classify program adaptations reported during in-depth interviews and focus group discussions with worksite managers, program staff, and peer educators involved in program delivery, and program participants and drop-outs. We used thematic analysis to identify key themes in the data and classified reported program adaptations using the FRAME classification system.

Results
Adaptations were led by worksite managers, peer educators, and program staff members. They occurred both pre- and during program implementation and were both planned (proactive) and unplanned (proactive and reactive). The most frequently reported adaptations to the individual-level intervention were curriculum changes to tailor lessons to the local context, make the program more appealing to the workers at the site, or add a wider variety of exercise options. Other content adaptations included improvements to the screening protocol, intervention scheduling, and outreach plans to tailor participant recruitment and retention to the sites. Environment-level content adaptations included expanding or leveraging healthy food and exercise options at the worksites. Challenges to adaptation included scheduling and worksite-level challenges. Participants discussed the need to continue adapting the program in the future to continue making it relevant for worksite settings and engaging for employees.

Conclusion
This study describes and classifies site-specific modifications to a structured lifestyle change education program with worksite-wide health improvements in India. This adds to the literature on implementation adaptation in general and worksite wellness in India, a country with a large and growing workforce with, or at risk of, serious cardiometabolic diseases. This information is key for program scale-up, dissemination, and implementation in other settings.

Trial registration
Clinicaltrials.gov NCT02813668. Registered June 27, 2016
Entropy defect: Algebra and thermodynamics
Authors: Livadiotis George , McComas David J. 
Published: November 2023

Abstract
We investigate the way the entropy of a system can be partitioned into the entropies of its constituents in consistency with thermodynamics. This partitioning is described through the concept of an entropy defect, which measures the missing entropy between the sum of entropies of a system's constituents and the entropy of the combined system; this decrease of entropy corresponds to the order induced by the additional long-range correlations developed among the constituents of the combined system. We conclude that the most generalized addition rule is the one characterizing the kappa entropy; when the system resides in stationary states, the kappa entropy becomes the one associated with kappa distributions, while, in general, this entropy applies more broadly, in stationary or nonstationary states. Moreover, we develop the specific algebra of the addition rule with entropy defect. The addition rule forms a mathematical group on the set of any measurable physical-quantity (e.g., entropy). Finally, we use these algebraic properties to restate the generalized zeroth law of thermodynamics so that it is applicable for nonstationary as well as stationary states: If a body C measures the entropies of two other bodies, A and B, then, their combined entropy is measured as the connected A and B entropy, where the entropy defect is involved in all measurements.
Renal Cortical Glucose Uptake Is Decreased in Insulin Resistance and Correlates Inversely With Serum Free-fatty Acids
Authors: Rebelos Eleni , Mari Andrea , Honka Miikka-Juhani , Pekkarinen Laura , Latva-Rasku Aino , Laurila Sanna , Rajander Johan , Salminen Paulina , Iida Hidehiro , Ferrannini Ele , Nuutila Pirjo 
Published: November 2023

Abstract

Context
Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a noninvasive manner. We have recently demonstrated that fluorodeoxyglucose F18 (18F FDG) positron emission tomography can be used to analyze renal glucose uptake (GU) rates, and that the renal cortex is an insulin-sensitive tissue.

Objective
To confirm that renal GU is decreased in people with obesity and to test whether circulating metabolites are related to renal GU.

Design, Setting and Participants
Eighteen people with obesity and 18 nonobese controls were studied with [18F]FDG positron emission tomography during insulin clamp. Renal scans were obtained ∼60 minutes after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton nuclear magnetic resonance metabolomics.

Results
Cortical GU was higher in healthy nonobese controls compared with people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], P = .004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, P = .01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, P = .009), acetoacetate (r = -0.48, P = .008), citrate (r = −0.44, P = .01), and free fatty acids (r = −0.68, P &lt; .0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters.

Conclusion
These data confirm differences in renal cortical GU between people with obesity and healthy nonobese controls. Moreover, the negative correlations between renal cortex GU and free fatty acids, ketone bodies, and citrate are suggestive of substrate competition in the renal cortex.
Ranavalona I of Madagascar: African Jezebel or Patriot?
Authors: Campbell Gwyn 
Published: November 2023

Abstract
The conventional historical interpretation of the early nineteenth-century history of Madagascar is that it reflected two contrasting reigns, that of King Radama I (r. 1810–28), and that of his successor, Queen Ranavalona I (r. 1828–61). The dominant view of Radama is that he was an enlightened, progressive, and pro-European monarch who welcomed embassies from British-ruled Mauritius from 1816, signed a treaty of alliance with Britain in 1820, and within less than a decade banned slave exports, accepted a Resident British political agent at his court, encouraged a London Missionary Society mission in Madagascar, and with British military assistance quickly subjected the entire island to his rule. By contrast, Ranavalona, Radama's senior wife, was illiterate and, guided by superstition and ancestral beliefs, unpredictable and brutal. Upon Radama's untimely death in mid-1828, Ranavalona illicitly seized the throne, established a tyrannical administration, and pursued retrograde illiberal, xenophobic, and anti-Christian policies. This article critically examines the origins of the conventional interpretation of Ranavalona and argues for the rationality of core economic and military policies she adopted aimed at safeguarding Madagascar from European imperial domination.
Routes and Hubs in the Indian Ocean World: Methodological Reconsiderations
Authors: Schnepel Burkhard 
Published: November 2023

AbstractThis article looks at “routes” and “hubs” in the Indian Ocean world, arguing that using these two concepts within a mobility-oriented perspective will provide an insightful addition, and alternative, to investigations that are guided solely by spatial concepts, such as “hinterland” or “littoral.” The first major part of this article discusses various routes in the history of the Indian Ocean world. It addresses questions such as the competition between various routes, their interconnectedness, their internal structure, deviations from the main routes, and the role of local pilots in showing the way to colonial powers. The second major part looks at the nodal points along such routes, here called “hubs.” It will be argued that these hubs not only enable the movements of things, but also stop them, if only temporarily, thereby often transforming them in meaning, value, and function. Therefore, hubs are also identified as having an internal dimension in addition to an external one. These points will be discussed with reference to one paradigmatic case, namely the island of Mauritius in the southwestern part of Indian Ocean world. The issue of mobility is discussed in greater detail in two further sections. While arguing in favor of mobility-oriented perspectives and methods, it is held that an overinflated use of terms such as circulation or flow may also be misleading.
Unveiling the Efficacy of Gamma Knife Radiosurgery for Tectal Plate Gliomas
Authors: Kilic Durankus Nülifer , Samanci Yavuz , Düzkalir Ali Haluk , Peker Selcuk 
Published: November 2023

BACKGROUND AND OBJECTIVES:
Tectal plate gliomas (TPGs) are midbrain tumors that grow slowly and have a benign clinical course. Most TPGs are low-grade astrocytomas, but they can encompass various histological tumor types. Gamma Knife radiosurgery (GKRS) is being explored as a potentially safe and effective treatment option for TPGs, although research in this area is limited. This study aims to evaluate GKRS's efficacy and safety in patients with TPG and provide a comprehensive review of existing literature on the topic.

METHODS:
This retrospective, single-center study included 48 patients with consecutive TPG who underwent GKRS between September 2005 and June 2022. Patients diagnosed with TPGs based on radiological or tissue-based criteria and who had a minimum follow-up period of 12 months were eligible for inclusion. The primary end points were local control and the absence of GKRS-associated or tumor-associated mortality and morbidity.

RESULTS:
During a median follow-up of 28.5 months (range, 12-128), the radiological assessment showed tumor control in all cases, with 16.7% achieving a complete response and 68.8% achieving a partial response. Pseudoprogression occurred in 6.2% of cases, with onset ranging from 3 to 8 months. Clinical outcomes revealed no permanent neurological deterioration, with symptoms improving in 14.6% of patients and remaining stable in the others. One patient in the pseudoprogression group experienced transient Parinaud syndrome. One patient died during follow-up because of unrelated causes. The mean survival time after GKRS was 123.7 months. None of the clinical, radiological, or radiosurgical variables showed a correlation with partial/complete response, clinical improvement, or overall survival.

CONCLUSION:
There is limited research available on the management of TPGs, and this study presents the largest patient cohort treated with GKRS, along with a substantial follow-up duration. Despite its limitations, this study demonstrates the efficacy and low-risk profile of GKRS for TPGs.