bluuebunny/crossref_metadata_2025 huggingface dataset:
Health, psychosocial, and economic impacts of the COVID-19 pandemic on people with chronic conditions in India: a mixed methods study
Authors: Singh Kavita , Kondal Dimple , Mohan Sailesh , Jaganathan Suganthi , Deepa Mohan , Venkateshmurthy Nikhil Srinivasapura , Jarhyan Prashant , Anjana Ranjit Mohan , Narayan K. M. Venkat , Mohan Viswanathan , Tandon Nikhil , Ali Mohammed K. , Prabhakaran Dorairaj , Eggleston Karen
Published: April 2021

Background

People with chronic conditions are disproportionately prone to be affected by the COVID-19 pandemic but there are limited data documenting this. We aimed to assess the health, psychosocial and economic impacts of the COVID-19 pandemic on people with chronic conditions in India.

Methods

Between July 29, to September 12, 2020, we telephonically surveyed adults (n = 2335) with chronic conditions across four sites in India. Data on participants’ demographic, socio-economic status, comorbidities, access to health care, treatment satisfaction, self-care behaviors, employment, and income were collected using pre-tested questionnaires. We performed multivariable logistic regression analysis to examine the factors associated with difficulty in accessing medicines and worsening of diabetes or hypertension symptoms. Further, a diverse sample of 40 participants completed qualitative interviews that focused on eliciting patient’s experiences during the COVID-19 lockdowns and data analyzed using thematic analysis.

Results

One thousand seven hundred thirty-four individuals completed the survey (response rate = 74%). The mean (SD) age of respondents was 57.8 years (11.3) and 50% were men. During the COVID-19 lockdowns in India, 83% of participants reported difficulty in accessing healthcare, 17% faced difficulties in accessing medicines, 59% reported loss of income, 38% lost jobs, and 28% reduced fruit and vegetable consumption. In the final-adjusted regression model, rural residence (OR, 95%CI: 4.01,2.90–5.53), having diabetes (2.42, 1.81–3.25) and hypertension (1.70,1.27–2.27), and loss of income (2.30,1.62–3.26) were significantly associated with difficulty in accessing medicines. Further, difficulties in accessing medicines (3.67,2.52–5.35), and job loss (1.90,1.25–2.89) were associated with worsening of diabetes or hypertension symptoms. Qualitative data suggest most participants experienced psychosocial distress due to loss of job or income and had difficulties in accessing in-patient services.

Conclusion

People with chronic conditions, particularly among poor, rural, and marginalized populations, have experienced difficulties in accessing healthcare and been severely affected both socially and financially by the COVID-19 pandemic.
Expectations of citizens from the government in response to COVID-19 pandemic: a cross-sectional study in Iran
Authors: Zarei Leila , Shahabi Saeed , Sadati Ahmad Kalateh , Tabrizi Reza , Heydari Seyed Taghi , Lankarani Kamran Bagheri
Published: April 2021

Background

The government is the main body in charge of controlling epidemics; hence, expectations from the intention and capacities of the government would affect the flexibility and behaviors of citizens. Given the severity of COVID-19 pandemic and the urgent need for cooperation of people in the prevention and combat processes, understanding the public perspectives would be crucial and instructive. This study aimed to explore such perspectives towards the current pandemic among the Iranian. Indeed, we sought to provide a favorable platform for effective policies in the face of the COVID-19 pandemic through recognizing public expectations.

Methods

This cross-sectional survey used an open-ended online questionnaire to investigate the common perspectives of the Iranian towards the response of government to COVID-19 pandemic. The participants were selected using snowball and convenient sampling techniques across the country. The collected data were analyzed and described using a thematic analysis.

Results

In general, 2547 participants agreed to participate in this study and completed the online questionnaire. According to the findings, the Iranian exhibited several expectations regarding the response of the government to COVID-19 pandemic. Three main themes were extracted based on these expectations: (1) health-related expectations, (2) policy-related expectations, and (3) Information-related expectations. In this study, a majority of participants highlighted the need to consider and follow-up the patients and their families, providing the financial and hygiene support during the pandemic, applying strict restrictions, and using close monitoring and controlling procedures. Furthermore, they mentioned that authorities and news agencies should observe the principals honesty and transparency.

Conclusions

Our findings revealed that people expect the government and other responsible institutions to minimize the burden of this pandemic through adopting effective policies. Also, they could help policy-makers become aware of the expectations of people and develop better strategies.
Fighting mosquito bite during a crisis: capabilities of Florida mosquito control districts during the COVID-19 pandemic
Authors: Moise Imelda K. , Ortiz-Whittingham Lola R. , Omachonu Vincent , Clark Marah , Xue Rui-De
Published: April 2021

Background

The stay-at-home orders imposed in early April 2020 due to the COVID-19 pandemic in various states complicated mosquito control activities across the United States (US), and Florida was no exception. Mosquito control programs are the first line of defense against mosquito-borne pathogens. The purpose of this study was to examine the capabilities of Florida mosquito programs to implement key mosquito measures during the COVID-19 pandemic lockdown.

Methods

Using a self-administered online survey, we examined the capabilities of all Florida mosquito control programs (both state-approved mosquito districts, N = 63; and open programs, N = 27) at a time when the state of Florida was still under heightened awareness of, stay-at-home orders and planning a phase 1 reopening over the COVID-19 pandemic (June to July 2020). The final sample included mosquito control programs structured as the Board of County Commissioners (BOCC) (n = 42), independent tax district (n = 16), municipal (n = 10), and health or emergency department (n = 5). We used descriptive statistics to summarize information about the characteristics of responding programs, their implemented mosquito control and surveillance activities.  wWe used bivariate analysis to compare the characteristics of responding programs and the self-reported mosquito measures.

Results

Of the recruited mosquito control programs, 73 completed the survey (81.1% response rate; 73/90). Of these, 57.5% (n = 42) were Board of County Commissioners (BOCC) mosquito control programs, 21.9% (n = 16) were independent tax district programs, 13.7% (n = 10) were municipal mosquito control programs, and only 6.8% (n = 5) were either health or emergency department mosquito control programs. Except for arbovirus surveillance, most programs either fully or partially performed larval (61.8%) and adult (78.9%) surveillance; most programs conducted species-specific control for Aedes aegypti (85.2%, n = 54), Aedes albopictus (87.3%, n = 55), Culex quinquefasciatus (92.1%, n = 58), and Culex nigripalpus (91.9%, n = 57).

Conclusions

Findings underscore the importance of ongoing mosquito control activities, and suggest that Florida mosquito control programs are vigilant and have significant capability to handle potential mosquito-borne disease threats, but arbovirus surveillance systems (laboratory testing of mosquito pools and testing of human and nonhuman specimens for arboviruses) are needed during pandemics as well.
Outcomes of surgery for giant hepatic hemangioma
Authors: Xie Qing-song , Chen Zi-xiang , Zhao Yi-jun , Gu Heng , Geng Xiao-ping , Liu Fu-bao
Published: April 2021

Background

The surgical indications for liver hemangioma remain unclear.

Methods

Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach–Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases.

Results

Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach–Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy.

Conclusion

The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.
Physiotherapists’ perceptions of and willingness to use telerehabilitation in Kuwait during the COVID-19 pandemic
Authors: Albahrouh Sarah Ibraheem , Buabbas Ali Jasem
Published: April 2021

Background

Telerehabilitation has been considered a suitable alternative healthcare delivery system during the COVID-19 outbreak, and many studies have promoted its feasibility in delivering physical care to patients who live with pain and disability. Physiotherapists’ perceptions and willingness are two key factors that influence the provision of remote physiotherapy.

Aim

To investigate physiotherapists’ perceptions of and willingness to use telerehabilitation in Kuwait during the COVID-19 pandemic and to explore the barriers that may hinder the use of telerehabilitation in this sector.

Methods

The following methods were used: (1) a cross-sectional survey and (2) face-to-face semi-structured interviews. In the cross-sectional survey, an electronic questionnaire was sent to 747 physiotherapists who were working in the governmental health sector. The questionnaire included four sections: perceptions of telerehabilitation, comfort with technology, willingness to use telerehabilitation, and barriers to using telerehabilitation. Six interviews were conducted with physiotherapy managers to explore the barriers and facilitators of telerehabilitation practice.

Data analysis

In this study, descriptive data analysis was conducted, and a cross-tabulation technique was used to find the associations between the variables, in which chi-square tests were used to identify the significance of the results, where p < 0.05. Thematic content analysis was used for the interviews.

Results

Only 273 completed questionnaires were received, giving a response rate of 36.5%. Most of the respondents (237; 86.8%) considered telerehabilitation a viable option to deliver healthcare to patients during the COVID-19 pandemic. In spite of the lack of information and communication technology (ICT) (156; 57.1%), 89% (243) of the respondents were willing to integrate telerehabilitation into their conventional practice, as cultural and social norms were not against the use of telerehabilitation systems. The results indicate that the more the physiotherapists used the internet and email in their work and the more comfortable they were with technology, the more willing they were to use telerehabilitation systems (p = 0.01). The physiotherapy managers reported that patients’ privacy and the confidentiality of their data were considered barriers.

Conclusion

In Kuwait, physiotherapists show overall positive perceptions towards and a willingness to use telerehabilitation to facilitate patients’ access to physiotherapy services. There are several barriers to employing telerehabilitation. Accordingly, recommendations are suggested.
A data process of human knee joint kinematics obtained by motion-capture measurement
Authors: Wang Jian-ping , Wang Shi-hua , Wang Yan-qing , Hu Hai , Yu Jin-wei , Zhao Xuan , Liu Jin-lai , Chen Xu , Li Yu
Published: April 2021

Background

The motion capture has been used as the usual method for measuring movement parameters of human, and most of the measuring data are obtained by partial manual process based on commercial software. An automatic kinematics data process was developed by programming on MATLAB software in this paper.

Methods

The motion capture measurement of healthy volunteers was carried out and the MATLAB program was used for data process. Firstly, the coordinate data of markers and anatomical points on human lower limb measured by motion capture system were read and repaired through the usual and the patch program. Meantime, the local coordinate systems of human femur and tibia were established with anatomical points. Then flexion/extension, abduction/adduction and internal/external rotation of human knee tibiofemoral joint were obtained by special coordinate transformation program.

Results

Using the above methods, motion capture measurements and batch data processing were carried out on squatting and climbing stairs of 29 healthy volunteers. And the motion characteristics (flexion/extension, internal/external rotation and adduction/abduction) of the knee joint were obtained. For example, the maximum internal/external rotation in squatting and climbing stairs were respectively was 30.5 degrees and 14 degrees, etc. Meantime, the results of this paper also were respectively compared with the results processed by other research methods, and the results were basically consistent, thus the reliability of our research method was verified. After calibration processing, the compiled MATLAB program of this paper can directly be used for efficient batch processing and avoiding manual modeling one by one.

Conclusion

A novel Patch Program of this paper has been developed, which can make reasonable compensation for missing and noise signals to obtain more complete motion data. At the same time, a universal data processing program has also been developed for obtaining the relative movement of various components of the human body, and the program can be modified for detail special analysis. These motion capture technologies can be used to judge whether the human body functions are abnormal, provide a reference for rehabilitation treatment and design of rehabilitation equipment, and evaluate the effectiveness before and after surgery.
Impact of the subcutaneous formulations of trastuzumab and rituximab on efficiency and resource optimization in Spanish hospitals: H-Excelencia study
Authors: Abad-Sazatornil María Reyes , Arenaza Ainhoa , Bayo Juan , García Mata Jesus , Guinea De Castro José María , León Josefa , Letellez Javier , Reguero Virginia , Martínez Chamorro Carmen , Salar Antonio
Published: April 2021

Background

Subcutaneous (SC) versus intravenous (IV) administration is advantageous in terms of patient convenience and hospital efficiency. This study aimed to compare the effect of optimizing the processes involved in SC versus IV administration of rituximab and trastuzumab on hospital capacity and service quality.

Methods

This cross-sectional resource utilization study interviewed oncologists, hematologists, nurses, and pharmacists from 10 hospitals in Spain to estimate changes in processes associated with conversion from IV to SC rituximab and trastuzumab, based on clinical experience and healthcare use from administrative databases.

Results

Efficient use of SC formulations increased the monthly capacity for parenteral administration by 3.35% (potentially increasable by 5.75% with maximum possible conversion according to the product label). The weekly capacity for hospital pharmacy treatment preparation increased by 7.13% due to conversion to SC formulation and by 9.33% due to transferring SC preparation to the cancer treatment unit (potentially increasable by 12.16 and 14.10%, respectively). Monthly hospital time decreased by 33% with trastuzumab and 47% with rituximab. In a hypothetical hospital, in which all processes for efficient use of SC rituximab and/or trastuzumab were implemented and all eligible patients received SC formulations, the estimated monthly capacity for preparation and administration increased by 23.1% and estimated hospital times were reduced by 60–66%.

Conclusions

Conversion of trastuzumab and rituximab to SC administration could improve the efficiency of hospitals and optimize internal resource management processes, potentially increasing care capacity and improving the quality of care by reducing time spent by patients at hospitals.
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

Background

ESCRT-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.

Results

Here, 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.

Conclusions

We 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

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

Background

Most 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 presentation

We 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.

Conclusions

We 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

Thyroid 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

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

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

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

Background

The 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.

Methods

We 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.

Results

Of 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.

Conclusions

Innovative 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

Background

Medicinal 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.

Methods

This 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.

Results

The 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.

Conclusions

People 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

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

The 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.
Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates
Authors: Okada Masayasu , Kawagoe Yosuke , Sato Yuta , Nozumi Motohiro , Ishikawa Yuya , Tamada Atsushi , Yamazaki Hiroyuki , Sekino Yuko , Kanemura Yonehiro , Shinmyo Yohei , Kawasaki Hiroshi , Kaneko Naoko , Sawamoto Kazunobu , Fujii Yukihiko , Igarashi Michihiro
Published: April 2021

GAP-43 is a vertebrate neuron-specific protein and that is strongly related to axon growth and regeneration; thus, this protein has been utilized as a classical molecular marker of these events and growth cones. Although GAP-43 was biochemically characterized more than a quarter century ago, how this protein is related to these events is still not clear. Recently, we identified many phosphorylation sites in the growth cone membrane proteins of rodent brains. Two phosphorylation sites of GAP-43, S96 and T172, were found within the top 10 hit sites among all proteins. S96 has already been characterized (Kawasaki et al., 2018), and here, phosphorylation of T172 was characterized. In vitro (cultured neurons) and in vivo, an antibody specific to phosphorylated T172 (pT172 antibody) specifically recognized cultured growth cones and growing axons in developing mouse neurons, respectively. Immunoblotting showed that pT172 antigens were more rapidly downregulated throughout development than those of pS96 antibody. From the primary structure, this phosphorylation site was predicted to be conserved in a wide range of animals including primates. In the developing marmoset brainstem and in differentiated neurons derived from human induced pluripotent stem cells, immunoreactivity with pT172 antibody revealed patterns similar to those in mice. pT172 antibody also labeled regenerating axons following sciatic nerve injury. Taken together, the T172 residue is widely conserved in a wide range of mammals including primates, and pT172 is a new candidate molecular marker for growing axons.
Tagasaste, leucaena and paulownia: three industrial crops for energy and hemicelluloses production
Authors: Palma Alberto , Loaiza Javier Mauricio , Díaz Manuel J. , García Juan Carlos , Giráldez Inmaculada , López Francisco
Published: April 2021

Background

Burning fast-growing trees for energy production can be an effective alternative to coal combustion. Thus, lignocellulosic material, which can be used to obtain chemicals with a high added value, is highly abundant, easily renewed and usually inexpensive. In this work, hemicellulose extraction by acid hydrolysis of plant biomass from three different crops (Chamaecytisus proliferus, Leucaena diversifolia and Paulownia trihybrid) was modelled and the resulting solid residues were used for energy production.

Results

The influence of the nature of the lignocellulosic raw material and the operating conditions used to extract the hemicellulose fraction on the heat capacity and activation energy of the subsequent combustion process was examined.

The heat power and the activation energy of the combustion process were found to depend markedly on the hemicellulose content of the raw material. Thus, a low content in hemicelluloses resulted in a lower increased energy yield after acid hydrolysis stage.

The process was also influenced by the operating conditions of the acid hydrolysis treatment, which increased the gross calorific value (GCV) of the solid residue by 0.6–9.7% relative to the starting material. In addition, the activation energy of combustion of the acid hydrolysis residues from Chamaecytisus proliferus (Tagasaste) and Paulownia trihybrid (Paulownia) was considerably lower than that for the starting materials, the difference increasing with increasing degree of conversion as well as with increasing temperature and acid concentration in the acid hydrolysis.

The activation energy of combustion of the solid residues from acid hydrolysis of tagasaste and paulownia decreased markedly with increasing degree of conversion, and also with increasing temperature and acid concentration in the acid hydrolysis treatment. No similar trend was observed in Leucaena diversifolia (Leucaena) owing to its low content in hemicelluloses.

Conclusions

Acid hydrolysis of tagasaste, leucaena and paulownia provided a valorizable liquor containing a large amount of hemicelluloses and a solid residue with an increased heat power amenable to efficient valorization by combustion. There are many potential applications of the hemicelluloses-rich and lignin-rich fraction, for example as multi-components of bio-based feedstocks for 3D printing, for energy and other value-added chemicals.
Periostin loss-of-function protects mice from post-traumatic and age-related osteoarthritis
Authors: Attur Mukundan , Duan Xin , Cai Lei , Han Tianzhen , Zhang Weili , Tycksen Eric D. , Samuels Jonathan , Brophy Robert H. , Abramson Steven B. , Rai Muhammad Farooq
Published: April 2021

Background

Elevated levels of periostin (Postn) in the cartilage and bone are associated with osteoarthritis (OA). However, it remains unknown whether Postn loss-of-function can delay or prevent the development of OA. In this study, we sought to better understand the role of Postn in OA development and assessed the functional impact of Postn deficiency on post-traumatic and age-related OA in mice.

Methods

The effects of Postn deficiency were studied in two murine experimental OA models using Postn−/− (n = 32) and littermate wild-type (wt) mice (n = 36). Post-traumatic OA was induced by destabilization of the medial meniscus (DMM) in 10-week-old mice (n = 20); age-related OA was analyzed in 24-month-old mice (n = 13). Cartilage degeneration was assessed histologically using the OARSI scoring system, and synovitis was evaluated by measuring the synovial lining cell layer and the cells density in the synovial stroma. Bone changes were measured by μCT analysis. Serum levels of Postn were determined by ELISA. Expression of Postn and collagenase-3 (MMP-13) was measured by immunostaining. RNA-seq was performed on chondrocytes isolated from 21-day old Postn−/− (n = 3) and wt mice (n = 3) to discover genes and pathways altered by Postn knockout.

Results

Postn−/− mice exhibited significantly reduced cartilage degeneration and OARSI score relative to wt mice in post-traumatic OA after 8 weeks (maximum: 2.37 ± 0.74 vs. 4.00 ± 1.20, P = 0.011; summed: 9.31 ± 2.52 vs. 21.44 ± 6.01, P = 0.0002) and spontaneous OA (maximum: 1.93 ± 0.45 vs. 3.58 ± 1.16, P = 0.014; summed: 6.14 ± 1.57 vs. 11.50 ± 3.02, P = 0.003). Synovitis was significantly lower in Postn−/− mice than wt only in the DMM model (1.88 ± 1.01 vs. 3.17 ± 0.63; P = 0.039). Postn−/− mice also showed lower trabecular bone parameters such as BV/TV, vBMD, Tb.Th, and Tb.N and high Tb. Sp in both models. Postn−/− mice had negligible levels of serum Postn compared with wt. Immunofluorescent studies of cartilage indicated that Postn−/− mice expressed lower MMP-13 levels than wt mice. RNA-seq revealed that cell-cell-adhesion and cell-differentiation processes were enriched in Postn−/− mice, while those related to cell-cycle and DNA-repair were enriched in wt mice.

Conclusions

Postn deficiency protects against DMM-induced post-traumatic and age-related spontaneous OA. RNA-seq findings warrant further investigations to better understand the mechanistic role of Postn and its potential as a therapeutic target in OA.