bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence-assisted interpretation of Ki-67 expression and repeatability in breast cancer
Authors: Li Lina , Han Dandan , Yu Yongqiang , Li Jinze , Liu Yueping 
Published: January 2022

Abstract
Background
Ki-67 standard reference card (SRC) and artificial intelligence (AI) software were used to evaluate breast cancer Ki-67LI. We established training and validation sets and studied the repeatability inter-observers.

Methods
A total of 300 invasive breast cancer specimens were randomly divided into training and validation sets, with each set including 150 cases. Breast cancer Ki-67 standard reference card ranging from 5 to 90% were created. The training set was interpreted by nine pathologists of different ages through microscopic visual assessment (VA), SRC, microscopic manual counting (MC), and AI. The validation set was interpreted by three randomly selected pathologists using SRC and AI. The intra-group correlation coefficient (ICC) were used for consistency analysis.

Results
In the homogeneous and heterogeneous groups of validation sets, the consistency among the pathologists that used SRC and AI was very good, with an ICC of>0.905. In the validation set, using SRC and AI, three pathologists obtained results that were very consistent with the gold standard, having an ICC above 0.95, and the inter-observer agreement was also very good, with an ICC of>0.9.

Conclusions
AI has satisfactory inter-observer repeatability, and the true value was closer to the gold standard, which is the preferred method for Ki-67LI reproducibility; While AI software has not been popularized, SRC may be interpreted as breast cancer Ki-67LI’s standard candidate method.
PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibro-adipose vascular anomaly (FAVA)
Authors: Hori Yumiko , Hirose Katsutoshi , Ozeki Michio , Hata Kenji , Motooka Daisuke , Tahara Shinichiro , Matsui Takahiro , Kohara Masaharu , Higashihara Hiroki , Ono Yusuke , Tanaka Kaishu , Toyosawa Satoru , Morii Eiichi 
Published: January 2022

Abstract
Background
Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA.

Methods
We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway.

Results
Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases.

Conclusions
There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.
Timing of inspiratory muscle activity detected from airway pressure and flow during pressure support ventilation: the waveform method
Authors: Mojoli Francesco , Pozzi Marco , Orlando Anita , Bianchi Isabella M. , Arisi Eric , Iotti Giorgio A. , Braschi Antonio , Brochard Laurent 
Published: January 2022

Abstract
Background
Whether respiratory efforts and their timing can be reliably detected during pressure support ventilation using standard ventilator waveforms is unclear. This would give the opportunity to assess and improve patient–ventilator interaction without the need of special equipment.

Methods
In 16 patients under invasive pressure support ventilation, flow and pressure waveforms were obtained from proximal sensors and analyzed by three trained physicians and one resident to assess patient’s spontaneous activity. A systematic method (the waveform method) based on explicit rules was adopted. Esophageal pressure tracings were analyzed independently and used as reference. Breaths were classified as assisted or auto-triggered, double-triggered or ineffective. For assisted breaths, trigger delay, early and late cycling (minor asynchronies) were diagnosed. The percentage of breaths with major asynchronies (asynchrony index) and total asynchrony time were computed.

Results
Out of 4426 analyzed breaths, 94.1% (70.4–99.4) were assisted, 0.0% (0.0–0.2) auto-triggered and 5.8% (0.4–29.6) ineffective. Asynchrony index was 5.9% (0.6–29.6). Total asynchrony time represented 22.4% (16.3–30.1) of recording time and was mainly due to minor asynchronies. Applying the waveform method resulted in an inter-operator agreement of 0.99 (0.98–0.99); 99.5% of efforts were detected on waveforms and agreement with the reference in detecting major asynchronies was 0.99 (0.98–0.99). Timing of respiratory efforts was accurately detected on waveforms: AUC for trigger delay, cycling delay and early cycling was 0.865 (0.853–0.876), 0.903 (0.892–0.914) and 0.983 (0.970–0.991), respectively.

Conclusions
Ventilator waveforms can be used alone to reliably assess patient’s spontaneous activity and patient–ventilator interaction provided that a systematic method is adopted.
EU health information progress: the harvest of policy supporting projects and networks
Authors: Tijhuis Mariken J. , Abboud Linda A. , Achterberg Peter W. 
Published: January 2022

Abstract
Background
The European Commission supports the initiation of health information related projects and networks serving comparative population health monitoring and health system performance assessment. Many of these projects and networks have produced relevant data, standards, methods, indicators and knowledge that may be lost as these networks become inactive.
The aim of this project retrieval and review was to identify health information projects and networks and their produced output; and subsequently facilitate systematic access to this information for policy makers, researchers and interested others via a web-based repository.

Methods
The scope of this article covers 1. population health oriented topics and 2. health system/health services oriented topics. Out of scope are specific infectious diseases; individual rare diseases; and the occurrence and effects of specific medical treatments, interventions and diagnostics; cohort studies; or studies focusing on research methods.
We searched bibliographic databases and EU project databases for policy supporting projects and networks and selected those fulfilling our inclusion criteria after more in-depth inspection. We searched for their outputs. In addition, we reviewed country participation in these projects and networks.

Results
We identified 36 projects and networks, 16 of which are population health oriented, 6 are health systems and services oriented and 14 cover both. Their total volume of output is not easily retrievable, as many project websites have been discontinued. Some networks and/or their outputs have found continuance within European agencies and/or national institutions. Others are struggling or have gone lost, despite their policy relevance. Participation in the projects was not evenly distributed across Europe. Project information was made available through the Health Information Portal.

Conclusions
EU funded projects and networks have contributed greatly to the evidence-base for policy by providing comparative health information. However, more action is needed to evaluate and conserve their outputs and facilitate continued contribution to the field after project funding stops. The realization of a sustainable infrastructure for these projects and networks is urgent. The Health Information Portal can play an important role in conserving and reusing health information. Information inequalities may exist across Europe but need further investigating.
Influence of hydrothermal recharge on the evolution of eruption styles and hazards during the 2018–2019 activity at Kuchinoerabujima Volcano, Japan
Authors: Minami Yusuke , Matsumoto Keiko , Geshi Nobuo , Shinohara Hiroshi 
Published: January 2022

AbstractThe activity of the 2018–2019 eruption of Kuchinoerabujima Volcano in Japan changed from continuous ejection of ash-laden plumes between October 21 and the middle of December, to intermittent explosive activity accompanied by several pyroclastic density currents until January 2019. To understand the behaviors of magma and hydrothermal fluid that controlled the eruptive sequence, we carried out component analysis, X-ray diffractometry, and leachate analysis for ash samples. The proportion of non-altered volcanic ash particles is ~ 15% in the earlier phase, then it decreased to less than 10% in the later explosive phase. Accordingly, the mineral assemblage of the volcanic ash samples changed from plagioclase-dominant to sulfate minerals-dominant. Concentration of SO42− and Cl/SO4 values of the ash-leachates decreased toward the later activity. These results indicate that the proportion of fresh volcanic rocks decreased and sulfuric acid fluid-derived sulfate minerals increased toward the later activities. Consequently, the 2018–2019 eruption at Kuchinoerabujima Volcano changed from magmatic activity to phreatomagmatic activity. Weak glowing of the crater was observed during the magmatic activity, indicating the volcanic conduit was hot enough to dry up the sub-volcanic hydrothermal system. The following phreatomagmatic activity indicates that the hydrothermal fluid recharged after the magmatic eruption phase. Recharge of the hydrothermal fluid likely caused the variation of the eruption style, and is a process that may control the evolution of hazards during future eruption scenarios at similar active volcanoes in Japan and worldwide.
Graphical Abstract
Salvage thoracoscopic esophagectomy after carbon-ion radiotherapy in a patient with esophageal squamous cell carcinoma: a case report
Authors: Kuriyama Kengo , Sohda Makoto , Saito Hideyuki , Ubukata Yasunari , Nakazawa Nobuhiro , Hara Keigo , Sakai Makoto , Sano Akihiko , Ogawa Hiroomi , Sano Takaaki , Yasuda Shigeo , Ishikawa Hitoshi , Shirabe Ken , Saeki Hiroshi 
Published: February 2022

Abstract
Background
Carbon-ion radiotherapy (CIRT) for esophageal cancer has been receiving significant attention given its high local control rates and minimal damage to normal tissues. However, the efficacy and safety of salvage surgery after CIRT for esophageal cancer remain unclear. We report the case of a patient who underwent salvage thoracoscopic surgery after CIRT.

Case presentation
A 51-year-old woman underwent upper gastrointestinal endoscopy and a type 0-IIa + 0-IIc esophageal squamous cell carcinoma located 27–29 cm from the patient’s incisors, classified as clinical stage I (T1bN0M0), was detected. She received CIRT (50.4 Gy [relative biological effectiveness, RBE]/12 fr) for localized esophageal cancer and achieved complete remission after 4 months. Six years after CIRT, follow-up endoscopic examination demonstrated a type 0-IIa + 0-IIc tumor in the previously treated area. In addition, a type 0-IIa lesion located 20–22 cm from the incisors was found. We diagnosed localized ESCC, classified as clinical stage I (T1bN0M0). Salvage thoracoscopic surgery was performed in the prone position with five access ports. Although the esophagus tightly adhered to the thoracic descending aorta and left main bronchus with severe fibrosis, the esophagus could be separated from the surrounding organs with careful forceps manipulation. The operation time and blood loss were 8 h 45 min and 253 mL, respectively. The patient was discharged from our hospital 17 days after the salvage surgery without any complications. Pathological findings revealed two squamous cell carcinomas. Both tumors were localized in the lamina propria mucosa, and lymph node metastasis was not detected. The tumors were diagnosed as pathological stage IA (pT1aN0M0) according to the TNM criteria. Moreover, pathological examinations showed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field. Following the surgery, the patient had no recurrence for 1 year and 6 months.

Conclusions
Thoracoscopic radical esophagectomy can be performed as salvage surgery. Careful and discreet surgery is integral to perform salvage surgery after CIRT since CIRT may cause severe adhesions and fibrosis in the irradiated field.
Morphological differences in tardigrade spermatozoa induce variation in gamete motility
Authors: Sugiura Kenta , Shiba Kogiku , Inaba Kazuo , Matsumoto Midori 
Published: January 2022

Abstract
Background
Fertilization is an event at the beginning of ontogeny. Successful fertilization depends on strategies for uniting female and male gametes that developed throughout evolutionary history. In some species of tardigrades, investigations of reproduction have revealed that released spermatozoa swim in the water to reach a female, after which the gametes are stored in her body. The morphology of the spermatozoa includes a coiled nucleus and a species-specific-length acrosome. Although the mating behaviour and morphology of tardigrades have been reported, the motility of male gametes remains unknown. Here, using a high-speed camera, we recorded the spermatozoon motilities of two tardigrades, Paramacrobiotus sp. and Macrobiotus shonaicus, which have longer and shorter spermatozoa, respectively.

Results
The movement of spermatozoa was faster in Paramacrobiotus sp. than in M. shonaicus, but the beat frequencies of the tails were equal, suggesting that the long tail improved acceleration. In both species, the head part consisting of a coiled nucleus and an acrosome did not swing, in contrast to the tail. The head part of Paramacrobiotus sp. spermatozoa swung harder during turning; in contrast, the tail of M. shonaicus moved more widely than the head. Finally, after mating, the spermatozoa that reached the female aggregated around the cloaca while waiting to enter her body in both tested species.

Conclusions
This study provides results for the first observations and analyses of individual spermatozoon motility in tardigrades. A comparison of the spermatozoon movements of the two tardigrades suggested that the motilities of the male gametes were affected by morphological differences, where the longer spermatozoa swam faster and the shorter ones showed more stable swimming. Swimming was mainly induced by tail movement, but the long head of Paramacrobiotus sp. spermatozoa might be especially important for turning. In addition, observations of mated female cloacae suggested that the head parts of the spermatozoa were required for aggregation around the cloaca of a mated female.
Protein content and HvNAM alleles in Nordic barley (Hordeum vulgare) during a century of breeding
Authors: Hagenblad Jenny , Vanhala Tytti , Madhavan Sharmila , Leino Matti W. 
Published: January 2022

Abstract
Background
Barley has been bred for more than a century in the Nordic countries, with dramatic improvements of yield traits. In this study we investigate if this has come at the cost of lower grain protein and micronutrient (iron, zinc) content, by analysing 80 accessions representing four different improvement stages. We further re-sequenced the two grain protein content associated genes HvNAM-1 and HvNAM-2 in full and performed expression analyses of the same genes to search for genetic associations with nutrient content.

Results
We found higher thousand grain weight in barley landraces and in accessions from the late improvement group compared to accessions from the mid of the twentieth century. Straw length was much reduced in late stage accessions. No significant temporal decrease in grain protein, iron or zinc content during twentieth century Nordic crop improvement could be detected. Out of the 80 accessions only two deviant HvNAM-1 sequences were found, represented by one accession each. These do not appear to be correlated to grain protein content. The sequence of HvNAM-2 was invariable in all accessions and no correlations between expression levels of HvNAM-1 and HvNAM-2 and with grain protein content was found.

Conclusions
In contrast to studies in wheat, where a strong negative correlation between straw length and grain protein and micronutrient content has been found, we do not see this relationship in Nordic barley. The last 60 years of breeding has reduced straw length but, contrary to expectations, not protein and micronutrient content. Variation in grain protein and micronutrient content was found among the Nordic barley accessions, but it is not explained by variation of HvNAM genes. This means that HvNAM is an unexploited source of genetic variation for nutrient content in Nordic barley.
Clinical acceptance of advanced visualization methods: a comparison study of 3D-print, virtual reality glasses, and 3D-display
Authors: Muff Julian Louis , Heye Tobias , Thieringer Florian Markus , Brantner Philipp 
Published: January 2022

Abstract
Background
To compare different methods of three-dimensional representations, namely 3D-Print, Virtual Reality (VR)-Glasses and 3D-Display regarding the understanding of the pathology, accuracy of details, quality of the anatomical representation and technical operability and assessment of possible change in treatment in different disciplines and levels of professional experience.

Methods
Interviews were conducted with twenty physicians from the disciplines of cardiology, oral and maxillofacial surgery, orthopedic surgery, and radiology between 2018 and 2020 at the University Hospital of Basel. They were all presented with three different three-dimensional clinical cases derived from CT data from their area of expertise, one case for each method. During this, the physicians were asked for their feedback written down on a pencil and paper questionnaire.

Results
Concerning the understanding of the pathology and quality of the anatomical representation, VR-Glasses were rated best in three out of four disciplines and two out of three levels of professional experience. Regarding the accuracy of details, 3D-Display was rated best in three out of four disciplines and all levels of professional experience. As to operability, 3D-Display was consistently rated best in all levels of professional experience and all disciplines. Possible change in treatment was reported using 3D-Print in 33%, VR-Glasses in 44%, and 3D-Display in 33% of participants. Physicians with a professional experience of more than ten years reported no change in treatment using any method.

Conclusions
3D-Print, VR-Glasses, and 3D-Displays are very well accepted, and a relevant percentage of participants with less than ten years of professional work experience could imagine a possible change in treatment using any of these three-dimensional methods. Our findings challenge scientists, technicians, and physicians to further develop these methods to improve the three-dimensional understanding of pathologies and to add value to the education of young and inexperienced physicians.
Morphological heterogeneity description enabled early and parallel non-invasive prediction of T-cell proliferation inhibitory potency and growth rate for facilitating donor selection of human mesenchymal stem cells
Authors: Imai Yuta , Kanie Kei , Kato Ryuji 
Published: January 2022

Abstract
Background
Within the extensively developed therapeutic application of mesenchymal stem cells (MSCs), allogenic immunomodulatory therapy is among the promising categories. Although donor selection is a critical early process that can maximize the production yield, determining the promising candidate is challenging owing to the lack of effective biomarkers and variations of cell sources. In this study, we developed the morphology-based non-invasive prediction models for two quality attributes, the T-cell proliferation inhibitory potency and growth rate.

Methods
Eleven lots of mixing bone marrow-derived and adipose-derived MSCs were analyzed. Their morphological profiles and growth rates were quantified by image processing by acquiring 6 h interval time-course phase-contrast microscopic image acquisition. T-cell proliferation inhibitory potency was measured by employing flow cytometry for counting the proliferation rate of peripheral blood mononuclear cells (PBMCs) co-cultured with MSCs. Subsequently, the morphological profile comprising 32 parameters describing the time-course transition of cell population distribution was used for explanatory parameters to construct T-cell proliferation inhibitory potency classification and growth rate prediction models. For constructing prediction models, the effect of machine learning methods, parameter types, and time-course window size of morphological profiles were examined to identify those providing the best performance.

Results
Unsupervised morphology-based visualization enabled the identification of anomaly lots lacking T-cell proliferation inhibitory potencies. The best performing machine learning models exhibited high performances of predictions (accuracy > 0.95 for classifying risky lots, and RMSE < 1.50 for predicting growth rate) using only the first 4 days of morphological profiles. A comparison of morphological parameter types showed that the accumulated time-course information of morphological heterogeneity in cell populations is important for predicting the potencies.

Conclusions
To enable more consistent cell manufacturing of allogenic MSC-based therapeutic products, this study indicated that early non-invasive morphology-based prediction can facilitate the lot selection process for effective cell bank establishment. It was also found that morphological heterogeneity description is important for such potency prediction. Furthermore, performances of the morphology-based prediction models trained with data consisting of origin-different MSCs demonstrated the effectiveness of sharing morphological data between different types of MSCs, thereby complementing the data limitation issue in the morphology-based quality prediction concept.