bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical cannabis for severe treatment resistant epilepsy in children: a case-series of 10 patients
Authors: Zafar Rayyan , Schlag Anne , Phillips Lawrence , Nutt David J 
Published: December 2021

ObjectivesTo report the findings of a case-series of 10 children suffering with intractable epilepsies in the UK to determine the feasibility for using whole-plant cannabis medicines to treat seizures in children.SettingThis study was conducted retrospectively through collecting clinical data from caretakers and clinicians on study outcome variables. Participants were recruited through the MedCann Support and End our Pain charity groups which are patient representative groups that support children who are using medical cannabis to treat their epilepsies. Medicines were prescribed to patients by clinicians in both National Health Service and private medical practices. Follow-up calls were conducted throughout the period January 2021 to May 2021 to keep data recorded up to date.ParticipantsTen children, 18 years old or under, with intractable epilepsies were recruited from two charities. There were no limitations on diagnosis, sex or ethnic origin.InterventionsParticipants were treated with a range of whole-plant medical cannabis oils. Individual dosing regimens were determined by clinicians.Primary outcome measureThe primary outcome measure was seizure frequency.ResultsSeizure frequency across all 10 participants reduced by 86% with no significant adverse events. Participants reduced use of antiepileptic drugs from an average of seven to one following treatment with medical cannabis. We also noted significant financial costs of £874 per month to obtain these medicines through private prescriptions.ConclusionsThis study establishes the feasibility of whole-plant medical cannabis as an effective and well-tolerated medicine for reducing seizure frequency in children suffering with intractable epilepsies. These findings justify the potential value of further research into the reported therapeutic benefit of whole-plant medicinal cannabis products.
Multidisciplinary teams caring for people with variations of sex characteristics: a scoping review
Authors: Gramc Martin , Streuli Jürg , de Clercq Eva 
Published: December 2021

BackgroundIn 2006 the Chicago consensus statement on the management of people with variations of sex characteristics (VSC) acknowledged the importance of a multidisciplinary team (MDT) approach. The consensus update from 2016 reinforced the call for multidisciplinary collaborations between medical professionals, parents and support groups, and proposed guidelines to improve shared decision making and patient-centred care embedded in ethical principles of self-determination and child participation. But there is little evidence that successfully MDTs have been implemented in clinical practice.Methods and aimsA scoping review was conducted to identify studies that address the collaboration and decision making process of MDTs providing care of people with VSC to identify ideal and actual (1) team composition; (2) models of collaboration and (3) ethical principles that MDTs follow. Six databases were systematically searched: CINAHIL, Medline, Psychinfo, Scopus, Socindex and Web of Science. No restriction was placed on the type of methodology used in the studies. To frame the research, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used.ResultsThe MDTs in the literature include mainly medical professionals: endocrinologists, urologists and surgeons. The collaboration among medical professionals in MDTs lacks cooperation as one team member sets the tasks of the team while each professional works separately. Despite the importance of psycho-social support the involvement of psychologists remains secondary. The implementation of ethical principles tends to exclude people with VSC.ConclusionThe care of people with VSC described in the papers is medically oriented as the team members are mainly medical professionals working separately. MDT tend to exclude people with VSC despite references to shared decision making processes and informed consent. There was no mention of adult care and lack of inclusion of patient’s perspective in the care process. The future research should do more empirical research of MDTs.
Designing the careful and kind clinic: an evidence-based approach
Authors: Poplau Sara , Linzer Mark , Allwood Dominique , Montori Victor , Armbruster Ryan , Koka Sreenivas 
Published: December 2021

BackgroundThere is evidence that creating a ‘healthy workplace’ can be of profound importance for clinicians, team members and patients. Yet there have been few papers that have proposed mechanisms to take decades of research and translate this into a practical list of options for leaders and managers to take into account when structuring a clinic based on care and kindness to achieve optimal health.EvidenceWe bring together 20 years of scholarship linking care of the caregivers with outcomes for caregivers and patients. The data are used to support both structures and cultures that will result in satisfied and thriving healthcare team members, as well as satisfied and healthy patients.ResultsThe clinic based on care of the caregivers will be structured to address key aspects of worklife that are known to cause either satisfaction or burnout. Aspects of care, such as time pressure, chaotic environments and worker control of their workplace, will be taken into account in clinical design; organisational culture will be supportive and cohesive, emphasising quality, values and communication. Experiences based on gender and race will be measured and continuously improved; and performance will be evaluated in a new, human-centred manner.OutcomesThe careful and kind clinic will be a remarkable place to work; in contrast to industrialised healthcare, this will be an environment where health can indeed be optimised, for both workers and patients.
Retrospective analysis of the appendiceal neoplasms: sampling technique may influence neoplasm detection
Authors: Issin Gizem , Demir Fatih , Simsek Hasan Aktug , Cagatay Diren Vuslat , Tayfur Mahir , Balci Mecdi Gurhan 
Published: December 2021

Abstract

Background and aims
Appendiceal neoplasms are uncommon entities that are usually determined incidentally during the histopathological examination. Different techniques used for the macroscopic sampling of appendectomy material may affect the determinating neoplasms.

Materials and methods
H&E-stained slides of 1280 cases who underwent appendectomy between 2013 and 2018 were reviewed retrospectively for histopathological features.

Results
Neoplasms were determined in 28 cases (3.09%); 1 lesion was observed in the proximal part of the appendix, 1 covering the entire length from proximal to distal and 26 in the distal part. In the 26 cases that observed in the distal part, the lesion was seen on both sides of the longitudinal section of the distal appendix in 20 cases, while it was seen on only one distal longitudinal section in the remaining 6 cases.

Conclusion
The vast majority of appendiceal neoplasms are seen in the distal part of the appendix, and, in some cases, neoplasms might be seen on only one side of the distal section. Sampling only one-half of the distal part of the appendix, where tumours are most often observed, could result in some neoplasms being missed. Therefore, sampling the whole distal part would be more beneficial to determine small diameter tumours that do not create macroscopic findings.
Serum etanercept concentrations in relation to disease activity and treatment response assessed by ultrasound, biomarkers and clinical disease activity scores: results from a prospective observational study of patients with rheumatoid arthritis
Authors: Gehin Johanna Elin , Syversen Silje Watterdal , Warren David John , Goll Guro Løvik , Sexton Joseph , Bolstad Nils , Hammer Hilde Berner 
Published: December 2021

ObjectivesTo identify the therapeutic range for etanercept and to assess the incidence of anti-etanercept antibody formation.MethodsAssociations between etanercept serum concentration and disease activity as well as treatment response were examined in a longitudinal observational study of rheumatoid arthritis patients starting etanercept. Disease activity was assessed by ultrasound (grey scale and power Doppler), 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index, plasma calprotectin and C reactive protein. Etanercept concentration and anti-etanercept antibodies were analysed using automated in-house fluorescence assays.ResultsA total of 89 patients were included, whereof 66% were biological disease-modifying antirheumatic drug (DMARD) naïve and 91% used concomitant synthetic DMARD. At 3 months, the median etanercept concentration was 1.8 (IQR 1.1–2.5) mg/L. Longitudinal associations were found between etanercept concentration and disease activity assessed by plasma calprotectin, C reactive protein and DAS28, but not between etanercept concentration and improvement in disease activity by any of the parameters at 3, 6 or 12 months of treatment. Etanercept concentrations were not significantly different among patients who achieved response or remission, compared with non-response or non-remission. Hence, no therapeutic range could be identified. None of the patients developed anti-etanercept antibodies.ConclusionDespite the use of sensitive and objective markers of inflammation, a therapeutic range could not be identified for etanercept. Hence, this study suggests that proactive therapeutic drug monitoring is unlikely to benefit rheumatoid arthritis patients treated with etanercept, but a potential benefit in certain clinical situations cannot be excluded.
Two-month administration of methylphenidate improves olfactory sensitivity and suppresses appetite in individuals with obesity
Authors: El Amine Fatmé , Heidinger Brandon , Cameron Jameason D. , Hafizi Kaamel , BaniFatemi Shakibasadat , Robaey Philippe , Vaillancourt Régis , Goldfield Gary S. , Doucet Éric 
Published: December 2021

Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake, and body weight (BW) on individuals with obesity. In a randomized, double-blind study, 12 participants (age 28.9 ± 6.7 years) with a body mass index (BMI) of 36.1 ± 4.5 kg/m2 were assigned to MPH (0.5 mg/kg) (n = 5) or placebo (n = 7) twice daily for 2 months. Appetite (visual analog scale), odour threshold (Sniffin’ Sticks®), energy intake (food menu), and BW (DEXA scan) were measured at day 1 and day 60. MPH intake significantly increased odour threshold scores (6.3 ± 1.4 vs. 9.4 ± 2.1 and 7.9 ± 2.3 vs. 7.8 ± 1.9, respectively; p = 0.029) versus placebo. There was a significantly greater suppression of appetite sensations (desire to eat (p = 0.001), hunger (p = 0.008), prospective food consumption (p = 0.003)) and an increase in fullness (p = 0.028) over time in the MPH versus placebo. MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.
Systematic Evaluation of the Effect of Bedside Ward Round Checklist on Clinical Outcomes of Critical Patients
Authors: Wen Xuemin , Wen YuXiang , Wang Ge , Li Hui , Zuo Hong 
Published: December 2021

Objective. To systematically evaluate the effect of bedside ward round checklists on the clinical outcomes of critical patients and thus provide a scientific and rational basis for decision-making in its clinical application. Methods. PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang databases were searched to collect the literature studies about randomized controlled trials (RCTs) and cohort studies involving the effect of bedside ward round checklists on the clinical outcomes of critical patients, and the retrieval time limit was from the establishment of the database to August 2019. After two researchers independently screened the literature studies, extracted the literature data, and evaluated the risk of bias in included studies, meta-analysis was carried out by using Stata 12.0 software. Results. Two RCTs and nine cohort studies were included in this study. The results of meta-analysis showed that compared with the ordinary bedside ward round, the application of checklist in bedside ward round could shorten the ICU hospitalization time (standardized mean difference (SMD) = – 0.37, 95% CI (– 0.78, 0.04),

P

≤ 0.001) and mechanical ventilation time (SMD = – 0.24, 95% CI (– 0.44, −0.04),

P

= 0.037) and reduce the incidence of ventilator-associated pneumonia (VAP) (SMD = 0.61, 95% CI (0.38, 0.99),

P

= 0.057) in critical patients. However, there were no significant differences in central venous catheter (CVC) retention time and incidence and mortality of deep venous thrombosis (DVT) between ordinary ward round and bedside ward round checklist. Conclusion. The existing evidence shows that compared with the ordinary ward round, the application of bedside ward round checklists can shorten ICU hospitalization time and mechanical ventilation time and reduce VAP incidence and ICU mortality in critical patients. However, due to the limitations of the quality of the included studies, the above conclusions need to be verified with more high-quality studies.
Integrated Metabolic Profiling and Transcriptional Analysis Reveals Therapeutic Modalities for Targeting Rapidly Proliferating Breast Cancers
Authors: Liao Chengheng , Glodowski Cherise Ryan , Fan Cheng , Liu Juan , Mott Kevin R. , Kaushik Akash , Vu Hieu , Locasale Jason W. , McBrayer Samuel K. , DeBerardinis Ralph J. , Perou Charles M. , Zhang Qing 
Published: December 2021

Abstract

Metabolic dysregulation is a prominent feature in breast cancer, but it remains poorly characterized in patient tumors. In this study, untargeted metabolomics analysis of triple-negative breast cancer (TNBC) and patient with estrogen receptor (ER)–positive breast cancer samples, as well as TNBC patient-derived xenografts (PDX), revealed two major metabolic groups independent of breast cancer histologic subtypes: a “Nucleotide/Carbohydrate-Enriched” group and a “Lipid/Fatty Acid-Enriched” group. Cell lines grown in vivo more faithfully recapitulated the metabolic profiles of patient tumors compared with those grown in vitro. Integrated metabolic and gene expression analyses identified genes that strongly correlate with metabolic dysregulation and predict patient prognosis. As a proof of principle, targeting Nucleotide/Carbohydrate-Enriched TNBC cell lines or PDX xenografts with a pyrimidine biosynthesis inhibitor or a glutaminase inhibitor led to therapeutic efficacy. In multiple in vivo models of TNBC, treatment with the pyrimidine biosynthesis inhibitor conferred better therapeutic outcomes than chemotherapeutic agents. This study provides a metabolic stratification of breast tumor samples that can guide the selection of effective therapeutic strategies targeting breast cancer subsets. In addition, we have developed a public, interactive data visualization portal (http://brcametab.org) based on the data generated from this study to facilitate future research.

Significance:
A multiomics strategy that integrates metabolic and gene expression profiling in patient tumor samples and animal models identifies effective pharmacologic approaches to target rapidly proliferating breast tumor subtypes.
Comparative Study on the Efficacy and Exposure of Molecular Target Agents in Non–small Cell Lung Cancer PDX Models with Driver Genetic Alterations
Authors: Jo Hitomi , Yagishita Shigehiro , Hayashi Yoshiharu , Ryu Shoraku , Suzuki Mikiko , Kohsaka Shinji , Ueno Toshihide , Matsumoto Yuji , Horinouchi Hidehito , Ohe Yuichiro , Watanabe Shun-ichi , Motoi Noriko , Yatabe Yasushi , Mano Hiroyuki , Takahashi Kazuhisa , Hamada Akinobu 
Published: December 2021

Abstract
Patient-derived xenografts (PDX) can adequately reflect clinical drug efficacy. However, the methods for evaluating drug efficacy are not fully established. We selected five non–small cell lung cancer (NSCLC) PDXs with genetic alterations from established PDXs and the corresponding molecular targeted therapy was administered orally for 21 consecutive days. Genetic analysis, measurement of drug concentrations in blood and tumors using LC/MS-MS, and analysis of drug distribution in tumors using matrix-assisted laser desorption/ionization mass spectrometry were performed. Fifteen (20%) PDXs were established using samples collected from 76 patients with NSCLC with genetic alterations. The genetic alterations observed in original patients were largely maintained in PDXs. We compared the drug efficacy in original patients and PDX models; the efficacies against certain PDXs correlated with the clinical effects, while those against the others did not. We determined blood and intratumor concentrations in the PDX model, but both concentrations were low, and no evident correlation with the drug efficacy could be observed. The intratumoral spatial distribution of the drugs was both homogeneous and heterogeneous for each drug, and the distribution was independent of the expression of the target protein. The evaluation of drug efficacy in PDXs enabled partial reproduction of the therapeutic effect in original patients. A more detailed analysis of systemic and intratumoral pharmacokinetics may help clarify the mode of action of drugs. Further development of evaluation methods and indices to improve the prediction accuracy of clinical efficacy is warranted.
Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates
Authors: Khera Eshita , Dong Shujun , Huang Haolong , de Bever Laureen , van Delft Floris L. , Thurber Greg M. 
Published: December 2021

Abstract
After several notable clinical failures in early generations, antibody–drug conjugates (ADC) have made significant gains with seven new FDA approvals within the last 3 years. These successes have been driven by a shift towards mechanistically informed ADC design, where the payload, linker, drug-to-antibody ratio, and conjugation are increasingly tailored to a specific target and clinical indication. However, fundamental aspects needed for design, such as payload distribution, remain incompletely understood. Payloads are often classified as “bystander” or “nonbystander” depending on their ability to diffuse out of targeted cells into adjacent cells that may be antigen-negative or more distant from tumor vessels, helping to overcome heterogeneous distribution. Seven of the 11 FDA-approved ADCs employ these bystander payloads, but the depth of penetration and cytotoxic effects as a function of physicochemical properties and mechanism of action have not been fully characterized. Here, we utilized tumor spheroids and pharmacodynamic marker staining to quantify tissue penetration of the three major classes of agents: microtubule inhibitors, DNA-damaging agents, and topoisomerase inhibitors. PAMPA data and coculture assays were performed to compare with the 3D tissue culture data. The results demonstrate a spectrum in bystander potential and tissue penetration depending on the physicochemical properties and potency of the payload. Generally, directly targeted cells show a greater response even with bystander payloads, consistent with the benefit of deeper ADC tissue penetration. These results are compared with computational simulations to help scale the data from in vitro and preclinical animal models to the clinic.
Multiple cues guarantee successful predation by a Neotropical wasp
Authors: Mendes-Silva Isamara , Queiroga Drielly , Calixto Eduardo S. , Torezan-Silingardi Helena M. , Del-Claro Kleber 
Published: December 2021

Abstract
Predatory social wasps are well studied in several aspects; however, foraging behaviour, especially that which takes place away from the nest at often unpredictable locations, or specialized behaviours to find and subdue prey are not well understood. In the Brazilian tropical savanna, the Polistinae wasp Brachygastra lecheguana is specialized in preying on some endophytic weevil larvae which develops inside floral buds. We hypothesized that these wasps utilize a combination of different mechanisms such as visual, chemical (odour) and possible tactile cues to find the weevil larvae. Using a combination of experimental manipulations (visual; chemical; visual/chemical) we tested the wasp’s ability to detect the endophytic larvae in the field. Additionally, we checked the ability of this wasp to detect vibrations produced by the weevils inside the buds. Our results suggest that the B. lecheguana wasp utilizes a sequence of eco-physiological mechanisms to find the endophytic larva inside floral buds: sight, smell, and perhaps touch. The use of multiple cues by this wasp guarantees such a high rate of predation on endophytic beetles that the wasp may have positive implications (reduction in weevils’ infestation) for the future of the host plant’s reproduction.
‘Becoming Black’
Authors: Tewolde Amanuel Isak 
Published: December 2021

Abstract
Little is known about racial identity claims of African migrants living in Israel who originate from countries where race is not a dominant identity marker. This article examines how Eritrean migrants, coming from a country where race-based social organisation is not prevalent, strategically adopted ‘Black’ as their identity marker in Israel. Online newspaper reports and conversational interviews with four Eritrean migrants were used as sources of data. During various anti-deportation protests, Eritrean migrants held signs with slogans referring to themselves as Black. Some of the slogans include: ‘Do Black lives matter in Israel?’, ‘Black or White I am human’, ‘Deported to death because I am Black’, and ‘Now I am White, will you deport me?’ I argue that for first generation Eritrean migrants in Israel, Black racial identity was adopted strategically as a political identity of social mobilisation and resistance in the face of a racialised and exclusionary migration policy.
World-Making at the Margins
Authors: Marquez Arturo 
Published: December 2021

Abstract
Transnational social networks are vital to West Africans in managing relationships but also in ascertaining viable ways of being and belonging in the diaspora. Drawing from ethnographic fieldwork in the metropolitan area of Barcelona, Catalonia, Spain, this paper examines the ‘Baay Faal paradox’ to address sites of contention in West African endeavours to bind a sense of self to transnational social networks. I propose urban world-making practices that sustain connections to transnational social networks from the margins of these relations signal what I am calling ‘affective tethering.’ The term ‘tethering’ in my analysis foregrounds an imagined distance between normative models of practice and purported deviations that result in precarious, unstable and patchy connections to transnational social networks. This approach sheds light on the complex relationship between a person’s sense of self and the transnational social networks that inform ideas of personhood in the context of global mobility and settlement.