bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advance care planning in Dutch primary care: a pre/post-implementation study
Authors: van der Plas Annicka , Glaudemans Jolien , Onwuteaka-Philipsen Bregje 
Published: March 2021

BackgroundDespite known advantages of advance care planning (ACP) and a positive attitude towards ACP by older people living in the community and general practitioners (GPs), such conversations are not yet commonplace in GP practices.AimTo implement ACP as part of routine care in general practice and thereby increasing the number of ACP conversations and advance directives; to investigate characteristics of older people with and without an ACP conversation.Methods(1) A pre-evaluation and post-evaluation study using questionnaire data from people aged 75 years or older living in the community. (2) A prospective study using data provided by healthcare professionals (people they started an ACP conversation with).ResultsAfter implementation of ACP, significantly more people had spoken to their GP about hospitalisations, intensive care admission and treatment preferences in certain circumstances, compared with before. Advance directives were drawn up more often. People who had an ACP conversation were older, have had a cerebrovascular accident, had a clear idea about future health problems, had a preference to start ACP before they were ill, already had an ACP conversation at pre-measurement and indicated at pre-measurement that their GP knows their preferences.ConclusionResults in number of ACP conversations and advance drectives were modest but positive. ACP was implemented as routine care. GPs select people with whom they have a conversation. This can be an efficient use of time, but there is a risk that certain groups may be underserved (for example, patients with multimorbidity or patients with less health skills).
Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia
Authors: Mamtilahun Muyassar , Jiang Lu , Song Yaying , Shi Xiaojing , Liu Chang , Jiang Yixu , Deng Lidong , Zheng Haoran , Shen Hui , Li Yongfang , Zhang Zhijun , Wang Yongting , Tang Yaohui , Yang Guo-Yuan 
Published: March 2021

BackgroundHealthy plasma therapy reverses cognitive deficits and promotes neuroplasticity in ageing brain disease. However, whether healthy plasma therapy improve blood–brain barrier integrity after stroke remains unknown.MethodsHere, we intravenously injected healthy female mouse plasma into adult female ischaemic stroke C57BL/6 mouse induced by 90 min transient middle cerebral artery occlusion for eight consecutive days. Infarct volume, brain atrophy and neurobehavioural tests were examined to assess the outcomes of plasma treatment. Cell apoptosis, blood–brain barrier integrity and fibroblast growth factor 21 knockout mice were used to explore the underlying mechanism.ResultsPlasma injection improved neurobehavioural recovery and decreased infarct volume, brain oedema and atrophy after stroke. Immunostaining showed that the number of transferase dUTP nick end labelling+/NeuN+cells decreased in the plasma-injected group. Meanwhile, plasma injection reduced ZO-1, occluding and claudin-5 tight junction gap formation and IgG extravasation at 3 days after ischaemic stroke. Western blot results showed that the FGF21 expression increased in the plasma-injected mice. However, using FGF21 knockout mouse plasma injecting to the ischaemic wild-type mice diminished the neuroprotective effects.ConclusionsOur study demonstrated that healthy adult plasma treatment protected the structural and functional integrity of blood–brain barrier, reduced neuronal apoptosis and improved functional recovery via FGF21, opening a new avenue for ischaemic stroke therapy.
SelfHAR
Authors: Tang Chi Ian , Perez-Pozuelo Ignacio , Spathis Dimitris , Brage Soren , Wareham Nick , Mascolo Cecilia 
Published: March 2021

Machine learning and deep learning have shown great promise in mobile sensing applications, including Human Activity Recognition. However, the performance of such models in real-world settings largely depends on the availability of large datasets that captures diverse behaviors. Recently, studies in computer vision and natural language processing have shown that leveraging massive amounts of unlabeled data enables performance on par with state-of-the-art supervised models.
In this work, we present SelfHAR, a semi-supervised model that effectively learns to leverage unlabeled mobile sensing datasets to complement small labeled datasets. Our approach combines teacher-student self-training, which distills the knowledge of unlabeled and labeled datasets while allowing for data augmentation, and multi-task self-supervision, which learns robust signal-level representations by predicting distorted versions of the input.
We evaluated SelfHAR on various HAR datasets and showed state-of-the-art performance over supervised and previous semi-supervised approaches, with up to 12% increase in F1 score using the same number of model parameters at inference. Furthermore, SelfHAR is data-efficient, reaching similar performance using up to 10 times less labeled data compared to supervised approaches. Our work not only achieves state-of-the-art performance in a diverse set of HAR datasets, but also sheds light on how pre-training tasks may affect downstream performance.
Impact of Baseline and On-Treatment Glycemia on Everolimus-Exemestane Efficacy in Patients with Hormone Receptor–Positive Advanced Breast Cancer (EVERMET)
Authors: Vernieri Claudio , Nichetti Federico , Lalli Luca , Moscetti Luca , Giorgi Carlo Alberto , Griguolo Gaia , Marra Antonio , Randon Giovanni , Rea Carmen G. , Ligorio Francesca , Scagnoli Simone , De Angelis Claudia , Molinelli Chiara , Fabbri Agnese , Ferraro Emanuela , Trapani Dario , Milani Andrea , Agostinetto Elisa , Bernocchi Ottavia , Catania Giovanna , Vantaggiato Amelia , Palleschi Michela , Moretti Anna , Basile Debora , Cinausero Marika , Ajazi Arta , Castagnoli Lorenzo , Lo Vullo Salvatore , Gerratana Lorenzo , Puglisi Fabio , La Verde Nicla , Arpino Grazia , Rocca Andrea , Ciccarese Mariangela , Pedersini Rebecca , Fabi Alessandra , Generali Daniele , Losurdo Agnese , Montemurro Filippo , Curigliano Giuseppe , Del Mastro Lucia , Michelotti Andrea , Cortesi Enrico , Guarneri Valentina , Pruneri Giancarlo , Mariani Luigi , de Braud Filippo 
Published: March 2021

Abstract

Purpose:
The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus.

Experimental Design:
We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane.

Results:
We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008).

Conclusions:
The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2− aBC.
Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase I Study
Authors: Seymour Erlene K. , Khan Husain Yar , Li Yiwei , Chaker Mahmoud , Muqbil Irfana , Aboukameel Amro , Ramchandren Radhakrishanan , Houde Christiane , Sterbis Golbon , Yang Jay , Bhutani Divaya , Pregja Silvana , Reichel Kathy , Huddlestun Amy , Neveux Colleen , Corona Kelly , Landesman Yosef , Shah Jatin , Kauffman Michael , Shacham Sharon , Mohammad Ramzi M. , Azmi Asfar S. , Zonder Jeffrey A. 
Published: March 2021

Abstract

Purpose:
The nuclear exporter protein exportin-1 (XPO1) is overexpressed in non-Hodgkin lymphoma (NHL) and correlates with poor prognosis. We evaluated enhancing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) activity in NHL by targeted inhibition of XPO1 using the selective inhibitor of nuclear export (SINE) compounds.

Patients and Methods:
We evaluated the antitumor activity of SINE compounds in combination with CHO chemotherapy in vitro and in vivo. Newly diagnosed NHL patients in a phase I dose-escalation study received R-CHOP for 6 cycles with weekly selinexor (60, 80, and 100 mg), then selinexor maintenance therapy for one year. RT-PCR, Western blotting, and RNA sequencing were performed on patient blood samples.

Results:
SINE compounds synergized with CHO in vitro in NHL cell lines and in vivo in our murine xenograft model. In our phase I study, selinexor was dosed at 60 mg (n = 6) and 80 mg (n = 6). The most common adverse events (AE) among 12 patients were fatigue (67%) and nausea (100%). Grade 3–4 AEs were infrequent. Ten evaluable patients had an overall response rate of 100% and complete remission rate of 90% with sustained remissions (median follow-up: 476 days). Maximally tolerated dose was not reached; however, the recommended phase II dose was 60 mg selinexor weekly after evaluating tolerability and discontinuation rates for each dose cohort. Analysis of patient blood samples revealed downregulation of XPO1 and several prosurvival markers.

Conclusions:
SINE compounds enhance the activity of CHO in vitro and in vivo. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).
Targeting Ovarian Cancer Stem Cells by Dual Inhibition of HOTAIR and DNA Methylation
Authors: Wang Weini , Fang Fang , Ozes Ali , Nephew Kenneth P. 
Published: March 2021

Abstract
Ovarian cancer is a chemoresponsive tumor with very high initial response rates to standard therapy consisting of platinum/paclitaxel. However, most women eventually develop recurrence, which rapidly evolves into chemoresistant disease. Persistence of ovarian cancer stem cells (OCSCs) at the end of therapy has been shown to contribute to resistant tumors. In this study, we demonstrate that the long noncoding RNA HOTAIR is overexpressed in HGSOC cell lines. Furthermore, HOTAIR expression was upregulated in OCSCs compared with non-CSC, ectopic overexpression of HOTAIR enriched the ALDH+ cell population and HOTAIR overexpression increased spheroid formation and colony-forming ability. Targeting HOTAIR using peptide nucleic acid-PNA3, which acts by disrupting the interaction between HOTAIR and EZH2, in combination with a DNMT inhibitor inhibited OCSC spheroid formation and decreased the percentage of ALDH+ cells. Disrupting HOTAIR-EZH2 with PNA3 in combination with the DNMTi on the ability of OCSCs to initiate tumors in vivo as xenografts was examined. HGSOC OVCAR3 cells were treated with PNA3 in vitro and then implanted in nude mice. Tumor growth, initiation, and stem cell frequency were inhibited. Collectively, these results demonstrate that blocking HOTAIR–EZH2 interaction combined with inhibiting DNA methylation is a potential approach to eradicate OCSCs and block disease recurrence.
Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers
Authors: Salem Ahmed Hamed , Tao Zhi-Fu , Bueno Orlando F. , Chen Jie , Chen Shuang , Edalji Rohinton , Elmore Steven W. , Fournier Keith M. , Harper Kaid C. , Hong Richard , Jenkins Gary J. , Ji Jianguo , Judge Russell A. , Kalvass John C. , Klix Russell C. , Ku Yi-Yin , Leverson Joel D. , Marks Richard A. , Marsh Kennan C. , Menon Rajeev M. , Park Chang H. , Phillips Darren C. , Pu Yu-Ming , Rosenberg Saul H. , Sanzgiri Yeshwant D. , Sheikh Ahmad Y. , Shi Yi , Stolarik Deanne , Suleiman Ahmed A. , Wang Xilu , Zhang Geoff G.Z. , Catron Nathaniel D. , Souers Andrew J. 
Published: March 2021

Abstract
Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (3, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.
Christ and His Representation, One or Two? The Image Theologies of Theodore of Stoudios, Leo of Chalcedon and Eustratius of Nicaea
Authors: Krausmüller Dirk 
Published: March 2021

Abstract
This article discusses the image theologies of Theodore of Stoudios, Leo of Chalcedon and Eustratius of Nicaea. It focuses on two topics: the relation between archetype and image and the identity of hypostasis. It is argued that Theodore’s image theology was contradictory, and that Leo of Chalcedon and Eustratius of Nicaea each developed one aspect of Theodore’s argumentation while neglecting the other.
Geneses and Aftereffects: The Subtleties of a Coup d’État in Zimbabwe and Their Post-coup Consequences
Authors: Dodo Obediah 
Published: March 2021

Abstract
In 2017, Zimbabwe recorded a military intervention that left President Mugabe out of office. The replacement government has created a raft of controversial measures and policies. The study therefore explored the implications of the coup to policy formulation and execution vis-à-vis the rights and security of the people. The study followed a democratic governance framework. It focused on demonstration participants and active soldiers during the coup. Twenty civilian demonstrators and ten soldiers were sampled from Harare which was the centre of the coup. Data were analysed using Narrative Latent Content method. The study established that policy formulation is driven by both emotions and the desire to protect committers of the coup from possible accountability. It also established that in-order to safeguard its interests, the regime has crafted repressive laws that are however unsustainable.
Sufi-Vedāntic Interactions and Literary Interconnections in the Gulzār-i ḥāl by Banwālīdās
Authors: Cappello Giuseppe 
Published: March 2021

Abstract
This paper focuses on the Gulzār-i ḥāl by Banwālīdās (1662–3), a Persian adaptation of the Sanskrit allegorical drama Prabodhacandrodaya composed by Kṛṣṇamiśra (not long after 1065). It is also hypothesised that Banwālīdās may have used a Braj Bhāṣā version of the same text – by the poet Nanddās entitled Prabodhacandrodaya Nāṭaka (c. 1570) –, as intermediary with the original Sanskrit. Regardless of the source that our author used to realise his Gulzār-i ḥāl, the filter used to adapt Advaitic elements to the Islamic mystical context was the Waḥdat al-Wujūd (“Unity of Being”), or the tradition of mysticism that was heavily inspiring Sufi traditions of South Asia at that time. Moreover, a codicological analysis of the Gulzār-i ḥāl’s manuscript tradition has brought to light that both Hindu and Muslim readership received the text. In this paper, I will show that the interpretative engagement of Banwālīdās carried on a tradition of philosophical studies that did not consider Sufi and Vedāntic metaphysics as separated entities but as elements that – in dialogue with each other – searched for a common answer to the ultimate truth.
Role of the climatological intertropical convergence zone in the seasonal footprinting mechanism of the El Niño-Southern Oscillation
Authors: Park Jae-Heung , Sung Mi-Kyung , Yang Young-Min , Zhao Jiuwei , An Soon-Il , Kug Jong-Seong 
Published: March 2021

AbstractThe North Pacific Oscillation (NPO), a primary atmospheric mode over the North Pacific in boreal winter, is known to trigger the El Niño-Southern Oscillation (ENSO) in the following winter, the process of which is recognized as the seasonal footprinting mechanism (SFM). Based on the analysis of model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5), we found that the SFM acts differently among models, and the correlation between the NPO and subsequent ENSO events, called the SFM efficiency, depends on the background mean state of the model. That is, SFM efficiency becomes stronger as the climatological position of the Pacific Intertropical Convergence Zone (ITCZ) moves poleward, representing an intensification of the northern branch of the ITCZ. When the Pacific ITCZ is located poleward, the wind-evaporation-sea surface temperature (SST) feedback becomes stronger as the precipitation response to the SST anomaly is stronger in higher latitudes compared to that of lower latitudes. In addition, such active ocean-atmosphere interactions enhance NPO variability, favoring the SFM to operate efficiently and trigger an ENSO event. Consistent with the model results, the observed SFM efficiency increased during the decades in which the northern branch of the climatological ITCZ was intensified, supporting the importance of the tropical mean state of precipitation around the Pacific ITCZ.
Cross-validation of active and passive microwave snowfall products over the continental United States
Authors: Mroz Kamil , Montopoli Mario , Battaglia Alessandro , Panegrossi Giulia , Kirstetter Pierre , Baldini Luca 
Published: March 2021

AbstractSurface snowfall rate estimates from the Global Precipitation Measurement (GPM) mission’s Core Observatory sensors and the CloudSat radar are compared to those from the Multi-Radar Multi-Sensor (MRMS) radar composite product over the continental United States during the period from November 2014 to September 2020. The analysis includes: the Dual-Frequency Precipitation Radar (DPR) retrieval and its single frequency counterparts, the GPM Combined Radar Radiometer Algorithm (CORRA), the CloudSat Snow Profile product (2C-SNOW-PROFILE) and two passive microwave retrievals, i.e., the Goddard PROFiling algorithm (GPROF) and the Snow retrievaL ALgorithm fOr gMi (SLALOM). The 2C-SNOW retrieval has the highest Heidke Skill Score (HSS) for detecting snowfall among the products analysed. SLALOM ranks second; it outperforms GPROF and the other GPM algorithms, all detecting only 30% of the snow events. Since SLALOM is trained with 2C-SNOW, it suggests that the optimal use of the information content in the GMI observations critically depends on the precipitation training dataset. All the retrievals underestimate snowfall rates by a factor of two compared to MRMS. Large discrepancies (RMSE of 0.7 to 1.5 mm h-1) between space-borne and ground-based snowfall rate estimates are attributed to the complexity of the ice scattering properties and to the limitations of the remote sensing systems: the DPR instrument has low sensitivity, while the radiometric measurements are affected by the confounding effects of the background surface emissivity and of the emission of supercooled liquid droplet layers.
Indocyanine Green Fluorescence Angiography of the Transverse Cervical Arterial Supply to Clavicle Flaps: An Anatomical Study
Authors: Muangsiri Pichtat , Tanjapatkul Rungkit , Sriswadpong Papat , Jomkoh Pojanan , Jirawatnotai Supasid 
Published: March 2021

ObjectiveTo describe the anatomy of the transverse cervical artery and to prove its perfusion to the clavicle using indocyanine green fluorescence angiography as an alternative vascularized bone for head and neck reconstruction.Study DesignCadaveric dissection.SettingAnatomy lab.MethodsTwenty‐two necks and shoulders from 11 fresh‐frozen cadavers were dissected. The transverse cervical artery diameter, length, emerging point, and the length of clavicle segment harvested were described. Photographic and near‐infrared video recordings of the bone’s medial and longitudinal cut surfaces were taken prior to, during, and after indocyanine green injection.ResultsThe transverse cervical artery originated from the thyrocervical trunk and emerged at the level of the medial one‐third of the clavicle in 22 of 22 (100%) specimens. The average length of the pedicle was 3.6 cm (range, 2.2‐4.4 cm), and the mean diameter was 2.5 mm (range, 1.8‐3.4 mm). The harvested bone had a mean length of 5.1 cm (range, 4.3‐5.8 cm). After injecting the indocyanine green, 22 of 22 (100%) specimens showed enhancement in the periosteum, bony cortex, and medulla.ConclusionThe middle third of the clavicle can be reliably harvested as a vascularized bone with its perfusion solely from the transverse cervical artery pedicle, as shown by the near‐infrared fluorescence imaging. The pedicle was sizable and constant in origin.
Determining the Prognosis of Bell’s Palsy Based on Severity at Presentation and Electroneuronography
Authors: Escalante Derek A. , Malka Ronit E. , Wilson Allison G. , Nygren Zachary S. , Radcliffe Kristofer A. , Ruhl Douglas S. , Vincent Aurora G. , Hohman Marc H. 
Published: March 2021

ObjectiveTo examine the demographics of Bell’s palsy and determine how House‐Brackmann (HB) grade at nadir and electroneuronography (ENoG) results correlate with HB grade after recovery and development of synkinesis.Study DesignRetrospective cohort study.SettingTertiary care military medical center.MethodsPatients with acute Bell’s palsy and adequate follow‐up, defined as 6 months or return to HB grade I function, were included. Demographic information, HB scores at nadir and recovery, and ENoG results were collected.ResultsA total of 112 patient records were analyzed. Ages ranged from 8 to 87 years with peaks at 21 to 25 and 61 to 65 years. Among patients, 16.3% reached a nadir at HB II, 41.9% at HB III, 5.4% at HB IV, 16.3% at HB V, and 20.1% at HB VI. The overall recovery rate was 73.2% to HB I function, 17.0% to HB II, and 9.8% to HB III. The chance of recovery to HB I decreased as the severity of paralysis increased (rs = −1.0, P <. 0001). Mean time to recovery to HB I was 6 weeks. Greater degeneration on ENoG suggested worse recovery (rs = 0.62, P =. 01). Patients with HB V and VI were most likely to develop synkinesis.ConclusionMore severe paralysis increased the chance of recovery to HB II or III function. The granularity of this study provides prognostic insights that may inform the counseling of patients with Bell’s palsy with respect to prognosis and recovery timeline.