bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ESCRT-III isoforms CHMP2A and CHMP2B display different effects on membranes upon polymerization
Authors: Alqabandi Maryam , de Franceschi Nicola , Maity Sourav , Miguet Nolwenn , Bally Marta , Roos Wouter H. , Weissenhorn Winfried , Bassereau Patricia , Mangenot Stéphanie 
Published: April 2021

AbstractBackgroundESCRT-III proteins are involved in many membrane remodeling processes including multivesicular body biogenesis as first discovered in yeast. In humans, ESCRT-III CHMP2 exists as two isoforms, CHMP2A and CHMP2B, but their physical characteristics have not been compared yet.ResultsHere, we use a combination of techniques on biomimetic systems and purified proteins to study their affinity and effects on membranes. We establish that CHMP2B binding is enhanced in the presence of PI(4,5)P2 lipids. In contrast, CHMP2A does not display lipid specificity and requires CHMP3 for binding significantly to membranes. On the micrometer scale and at moderate bulk concentrations, CHMP2B forms a reticular structure on membranes whereas CHMP2A (+CHMP3) binds homogeneously. Thus, CHMP2A and CHMP2B unexpectedly induce different mechanical effects to membranes: CHMP2B strongly rigidifies them while CHMP2A (+CHMP3) has no significant effect.ConclusionsWe therefore conclude that CHMP2B and CHMP2A exhibit different mechanical properties and might thus contribute differently to the diverse ESCRT-III-catalyzed membrane remodeling processes.
Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications—a methodological review
Authors: Paludan-Müller Asger S. , Créquit Perrine , Boutron Isabelle 
Published: April 2021

Abstract
Background
An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications.

Methods
We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources.

Results
We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications.

Conclusions
Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.
A paradigmatic autistic phenotype associated with loss of PCDH11Y and NLGN4Y genes
Authors: Nardello Rosaria , Antona Vincenzo , Mangano Giuseppe Donato , Salpietro Vincenzo , Mangano Salvatore , Fontana Antonina 
Published: April 2021

AbstractBackgroundMost studies relative to Y chromosome abnormalities are focused on the sexual developmental disorders. Recently, a few studies suggest that some genes located on Y chromosome may be related to different neurodevelopment disorders.Case presentationWe report a child with sexual developmental disorder associated with a peculiar phenotype characterized by severe language impairment and autistic behaviour associated with a mosaicism [45,X(11)/46,XY(89)] and a partial deletion of the short and long arm of Y chromosome (del Yp11.31q11.23) that also involves the loss of bothPCDH11YandNLGN4Ygenes. To our knowledge no study has ever reported the occurrence of the lack of bothPCDH11YandNLGN4Ylocated in the Y chromosome in the same patient.ConclusionsWe hypothesized a functional complementary role ofPCDH11YandNLGN4Ywithin formation/maturation of the cerebral cortex. The impairment of early language development may be mainly related to the lack ofPCDH11Ythat underlies the early language network development and the later appearance of the autistic behaviour may be mainly related to deficit of inhibitory glicinergic neurotransmissionNLGN4Y-linked.
Role of thyroid hormone-integrin αvβ3-signal and therapeutic strategies in colorectal cancers
Authors: Yang Yu-Chen S. H. , Ko Po-Jui , Pan Yi-Shin , Lin Hung-Yun , Whang-Peng Jacqueline , Davis Paul J. , Wang Kuan 
Published: April 2021

AbstractThyroid hormone analogues—particularly, l-thyroxine (T4) has been shown to be relevant to the functions of a variety of cancers. Integrin αvβ3 is a plasma membrane structural protein linked to signal transduction pathways that are critical to cancer cell proliferation and metastasis. Thyroid hormones, T4 and to a less extend T3 bind cell surface integrin αvβ3, to stimulate the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway to stimulate cancer cell growth. Thyroid hormone analogues also engage in crosstalk with the epidermal growth factor receptor (EGFR)-Ras pathway. EGFR signal generation and, downstream, transduction of Ras/Raf pathway signals contribute importantly to tumor cell progression. Mutated Ras oncogenes contribute to chemoresistance in colorectal carcinoma (CRC); chemoresistance may depend in part on the activity of ERK1/2 pathway. In this review, we evaluate the contribution of thyroxine interacting with integrin αvβ3 and crosstalking with EGFR/Ras signaling pathway non-genomically in CRC proliferation. Tetraiodothyroacetic acid (tetrac), the deaminated analogue of T4, and its nano-derivative, NDAT, have anticancer functions, with effectiveness against CRC and other tumors. In Ras-mutant CRC cells, tetrac derivatives may overcome chemoresistance to other drugs via actions initiated at integrin αvβ3 and involving, downstream, the EGFR-Ras signaling pathways.
Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles
Authors: Toledo-Corral C. M. , Alderete T. L. , Herting M. M. , Habre R. , Peterson A. K. , Lurmann F. , Goran M. I. , Weigensberg M. J. , Gilliland F. D. 
Published: April 2021

Abstract
Background
Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels.

Methods
In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA.

Results
Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1–7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4–10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4–10 month exposure period associated with lower morning serum cortisol (p < 0.05).

Conclusions
Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.
Absence of progesterone receptor membrane component 1 reduces migration and metastasis of breast cancer
Authors: Lee Sang R. , Lee Young Ho , Jo Seong Lae , Heo Jun H. , Kim Globinna , Lee Geun-Shik , An Beum-Soo , Baek In-Jeoung , Hong Eui-Ju 
Published: April 2021

Abstract
Background
Progesterone receptor membrane component 1 (Pgrmc1) is a non-classical progesterone receptor associated with the development of the mammary gland and xenograft-induced breast cancer. Importantly, Pgrmc1 is associated with the expression of estrogen receptor alpha and can be used for predicting the prognosis of breast cancer. Whether the genetic deletion of Pgrmc1 affects the progression of breast cancer is still unclear.

Methods
We used MMTV-PyMT transgenic mice that spontaneously develop breast tumors. In backcrossed FVB Pgrmc1 knockout (KO) mice, we monitored the development of the primary tumor and lung metastasis. In MCF-7 and MDA-MB-231 tumor cell lines, the migratory activity was evaluated after Pgrmc1 knockdown.

Results
There was no significant difference in the development of breast cancer in terms of tumor size at 13 weeks of age between WT and Pgrmc1 KO mice. However, Pgrmc1 KO mice had a significantly longer survival duration compared with WT mice. Furthermore, Pgrmc1 KO mice exhibited a significantly lower degree of lung metastasis. Compared with those of WT mice, the tumors of Pgrmc1 KO mice had a low expression of focal adhesion kinase and epithelial–mesenchymal transition markers. PGRMC1 knockdown resulted in a significantly reduced migration rate in breast cancer cell lines.

Conclusions
Pgrmc1 KO mice with breast cancer had a prolonged survival, which was accompanied by a low degree of lung metastasis. PGRMC1 showed a significant role in the migration of breast cancer cells, and may serve as a potential therapeutic target in breast cancer.
Allogeneic transplant procurement in the times of COVID-19: Quality report from the central European cryopreservation site
Authors: Wiercinska Eliza , Schlipfenbacher Vera , Bug Gesine , Bader Peter , Verbeek Mareike , Seifried Erhard , Bonig Halvard 
Published: April 2021

Abstract
Background
Because of limitations of transportation imposed by the COVID-19 pandemic, current recommendation calls for cryopreservation of allogeneic stem cell transplants before patient conditioning. A single cell therapy laboratory was selected to function as the central cryopreservation hub for all European registry donor transplants intended for the Australian-Pacific region. We examined properties of these transplants to ascertain how quality is maintained.

Methods
We analyzed 100 pandemic-related allogeneic mobilized blood-derived stem cell apheresis products generated at 30 collection sites throughout Europe, shipped to and cryopreserved at our center between April and November of 2020. Products were shipped in the cool, subsequently frozen with DMSO as cryoprotectant. Irrespective of origin, all products were frozen within the prescribed shelf-life of 72 h.

Results
Prior to cryopreservation, viable stem cell and leukocyte count according to the collection site and our reference laboratory were highly concordant (r2 = 0.96 and 0.93, respectively) and viability was > 90% in all instances. Median nominal post-thaw recovery of viable CD34+ cells was 42%. Weakly associated with poorer CD34+ cell recovery was higher leukocyte concentration, but not time lag between apheresis or addition of cryopreservant, respectively, and start of freezing. The correlation between pre- and post-thaw CD34+ cell dose was high (r2 = 0.85), hence predictable. Neutrophil and platelet engraftment were prompt with no evidence of dose dependency within the range of administered cell doses (1.31–15.56 × 106 CD34+ cells/kg).

Conclusions
General cryopreservation of allogeneic stem cell transplants is feasible. While more than half of the CD34+ cell content is lost, the remaining stem cells ensure timely engraftment.
A review of prospective pathways and impacts of COVID-19 on the accessibility, safety, quality, and affordability of essential medicines and vaccines for universal health coverage in Africa
Authors: Amimo Floriano , Lambert Ben , Magit Anthony , Hashizume Masahiro 
Published: April 2021

AbstractBackgroundThe ongoing pandemic of coronavirus disease 2019 (COVID-19) has the potential to reverse progress towards global targets. This study examines the risks that the COVID-19 pandemic poses to equitable access to essential medicines and vaccines (EMV) for universal health coverage in Africa.MethodsWe searched medical databases and grey literature up to 2 October 2020 for studies reporting data on prospective pathways and innovative strategies relevant for the assessment and management of the emerging risks in accessibility, safety, quality, and affordability of EMV in the context of the COVID-19 pandemic. We used the resulting pool of evidence to support our analysis and to draw policy recommendations to mitigate the emerging risks and improve preparedness for future crises.ResultsOf the 310 records screened, 134 were included in the analysis. We found that the disruption of the international system affects more immediately the capability of low- and middle-income countries to acquire the basket of EMV. The COVID-19 pandemic may facilitate dishonesty and fraud, increasing the propensity of patients to take substandard and falsified drugs. Strategic regional cooperation in the form of joint tenders and contract awarding, joint price negotiation and supplier selection, as well as joint market research, monitoring, and evaluation could improve the supply, affordability, quality, and safety of EMV. Sustainable health financing along with international technology transfer and substantial investment in research and development are needed to minimize the vulnerability of African countries arising from their dependence on imported EMV. To ensure equitable access, community-based strategies such as mobile clinics as well as fees exemptions for vulnerable and under-served segments of society might need to be considered. Strategies such as task delegation and telephone triage could help reduce physician workload. This coupled with payments of risk allowance to frontline healthcare workers and health-literate healthcare organization might improve the appropriate use of EMV.ConclusionsInnovative and sustainable strategies informed by comparative risk assessment are increasingly needed to ensure that local economic, social, demographic, and epidemiological risks and potentials are accounted for in the national COVID-19 responses.
The use of medicinal plants to prevent COVID-19 in Nepal
Authors: Khadka Dipak , Dhamala Man Kumar , Li Feifei , Aryal Prakash Chandra , Magar Pappu Rana , Bhatta Sijar , Thakur Manju Shree , Basnet Anup , Cui Dafang , Shi Shi 
Published: April 2021

AbstractBackgroundMedicinal plants are the fundamental unit of traditional medicine system in Nepal. Nepalese people are rich in traditional medicine especially in folk medicine (ethnomedicine), and this system is gaining much attention after 1995. The use of medicinal plants has increased during the COVID-19 pandemic as a private behavior (not under the control of government). A lot of misinterpretations of the use of medicinal plants to treat or prevent COVID-19 have been spreading throughout Nepal which need to be managed proactively. In this context, a research was needed to document medicinal plants used, their priority of use in society, their cultivation status, and the source of information people follow to use them. This study aimed to document the present status of medicinal plant use and make important suggestion to the concerned authorities.MethodsThis study used a web-based survey to collect primary data related to medicinal plants used during COVID-19. A total of 774 respondents took part in the survey. The study calculated the relative frequencies of citation (RFC) for the recorded medicinal plants. The relationship between plants recorded and different covariates (age, gender education, occupation, living place, and treatment methods) was assessed using Kruskal-Wallis test and Wilcoxon test. The relationship between the information sources people follow and the respondent characteristics was assessed using chi-square test.ResultsThe study found that the use of medicinal plants has increased during COVID-19 and most of the respondents recommended medicinal plants to prevent COVID-19. This study recorded a total of 60 plants belonging to 36 families. The leaves of the plants were the most frequently used. TheZingiber officinalewas the most cited species with the frequency of citation 0.398. Most of the people (45.61%) were getting medicinal plants from their home garden. The medicinal plants recorded were significantly associated with the education level, location of home, primary treatment mode, gender, and age class. The information source of plants was significantly associated with the education, gender, method of treatment, occupation, living with family, and location of home during the lockdown caused by COVID-19.ConclusionsPeople were using more medicinal plants during COVID-19 claiming that they can prevent or cure COVID-19. This should be taken seriously by concerned authorities. The authorities should test the validity of these medicinal plants and control the flow of false information spread through research and awareness programs.
eHealth for patients with rare diseases: the eHealth Working Group of the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN)
Authors: Paglialonga Alessia , Gaetano Raffaella , Robert Leema , Hurard Marine , Botella Luisa Maria , Barr Natasha , Jondeau Guillaume , Pini Alessandro 
Published: April 2021

Abstract
Background
The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) was launched in 2017 and involves, to date, 35 highly specialised multidisciplinary expert centres (from the 30 full Healthcare Provider members) coming from 11 countries and more than 70 patient organizations from 16 countries. The eHealth Working Group (WG) of VASCERN was set up to develop practical, patient-centred solutions and strategies for effective use of eHealth tools to answer the needs of patients with multisystemic vascular rare diseases.

The eHealth WG
Following the identified patients’ needs and following the guiding principles of collaboration and patient-centredness, the eHealth WG was created with the following aims: to develop a mobile app to help patients find expert centres and patient organizations, and to develop resources (Pills of Knowledge, PoK) for training and education via digital platforms (eLearning). The mobile app includes, to date, functionalities that allow users to find expert centres and patient organizations across Europe in the area of rare multisystemic vascular diseases. Discussed app developments include personalized digital patient passports, educational material, emergency management guidelines and remote consultations. Regarding training and education, a variety of PoK have been developed. The PoK cover several topics, target several user groups, and are delivered in various formats so that they are easy-to-use, easy-to-understand, informative, and viable for delivery and sharing through digital platforms (eLearning) including, e.g., the VASCERN YouTube™ channel.

Conclusion
Overall, the work carried out by the eHealth WG of VASCERN can be seen as a pilot experience that may serve as a basis to for collaborative development of patient-centred eHealth tools that answer the needs of patients with various rare diseases, not limited to rare multisystemic vascular diseases. By expanding the multidisciplinary approach here described, clinical and research networks can take advantage of eHealth services and use them as strategic assets in achieving the ultimate goal of ensuring equity of access to prevention programs, timely and accurate diagnosis and specialized care for patients with rare diseases throughout Europe.
Evaluating strategies to manage and endure challenging behaviors in mucopolysaccharidoses
Authors: Grant Nathan 
Published: April 2021

AbstractThe mucopolysaccharidoses (MPS) are a group of rare, genetic, lysosomal storage disorders characterized by progressive, multisystemic accumulation of glycosaminoglycans. Individuals with severe MPS often present with significant neurological involvement and may exhibit challenging behaviors, including hyperactivity, aggression, and sleep disturbance. These behaviors can cause adverse outcomes and necessitate the development of specific measures to support affected families. Through an analysis of the results reported by Hoffmann et al. in their recent study, this letter outlines important factors that must be considered when evaluating the impact of challenging behaviors associated with MPS, including treatment history, age, sibling and family relationships, the feasibility of daily caregiving, and caregiver burden. These recommendations can help guide future studies to identify the most effective coping strategies to support families of people with MPS who have challenging behaviors.