bluuebunny/crossref_metadata_2025 huggingface dataset:
Time to recovery from Eclampsia and its determinants in east Gojjam zone hospitals, Amhara, Ethiopia, 2017/18
Authors: Kassie Bekalu , Bazezew Yibelu , Sharew Yewbmirt , Yismaw Leltework , Desta Melaku , Alene Muluneh
Published: April 2021

Background

Eclampsia is a tonic clonic type of seizure among pre-eclamptic mothers. Time to recovery from eclampsia is to mean that the time when the mother recovered from severity features of pre-eclampsia. As far as the mother is not free from severity features, she is in a potential to end-up with repeated seizure (eclampsia). Therefore, combating eclampsia through controlling severity features is crucial to enhance maternal health quality, reduce maternal morbidity and mortality, and improve prenatal outcomes. There was no literature that describes the recovery time of eclampsia and its determinants in Ethiopia. Therefore, this study aimed to assess the recovery time from eclampsia and its determinants in East Gojjam zone hospitals.

Methods

An institutional based retrospective follow up study was conducted between January 2014 and December 2017 among 608 eclamptic mothers in East Gojjam zone Hospitals. Simple random sampling technique was used. Data were coded and entered to Epidata version 3.1 and was exported to SPSS version 20 and then to Stata 14. We used the adjusted hazard ratio (AHR) with 95% confidence interval at p-value less than 0.05 to measure strength of association.

Result

The median recovery time of eclampsia was 12 h with inter-quartile range of (1–48 h). The rate of recovery from eclampsia among mothers aged more than 20 years was reduced by half (AHR 0.50 (0.28, 0.89)) than the teenagers. The rate of recovery from eclampsia among mothers who had prolonged labor was 1.3 times (AHR 1.26 (1.01, 1.57)) than those whose labor was less than 12 h. About 32% of mothers with multiple convulsions recoverd later than (AHR 0.68 (0.52, 0.87)) those who had single convulsion. As compared to antepartum convulsion, the rate of recovery from postpartum eclampsia was 1.8 times faster (AHR 1.81(1.17, 2.81)).

Conclusion

The median recovery time from severity features among eclamptic mothers in East Gojjam zone hospitals was half a day. It is affected by age, duration of labor, number of convulsions and time of occurrence of the event. Special attention for elders, prevent recurrent convulsion and faster termination for the antepartum eclamptic mothers are recommended from this follow-up study.
Humanized anti-DEspR IgG4S228P antibody increases overall survival in a pancreatic cancer stem cell-xenograft peritoneal carcinomatosis ratnu/nu model
Authors: Gromisch Christopher M. , Tan Glaiza L. A. , Pasion Khristine Amber , Moran Ann-Marie , Gromisch Matthew S. , Grinstaff Mark W. , Carr Francis J. , Herrera Victoria L. M. , Ruiz-Opazo Nelson
Published: April 2021

Background

Pancreatic peritoneal carcinomatosis (PPC), with the worst median overall-survival (mOS), epitomizes the incurability of metastatic cancer. Cancer stem cells (CSCs) underpin this incurability. However, inhibitors of CSC-stemness fail to increase mOS in cancer patients despite preclinical tumor-reduction. This shortfall reinforces that preclinical efficacy should be defined by increased mOS in the presence of cancer comorbidities, CSC-heterogeneity and plasticity. The primary objectives of this study are: to test the dual endothelin-1/signal peptide receptor, DEspR, as a nodal therapeutic target in PPC, given DEspR induction in anoikis-resistant pancreatic CSCs, and to validate humanized anti-DEspR antibody, hu-6g8, as a potential therapeutic for PPC.

Methods

We used heterogeneous pools of CSCs selected for anoikis resistance from reprogrammed Panc1 and MiaPaCa2 tumor cells (TCs), and adherent TCs reprogrammed from CSCs (cscTCs). We used multiple anti-DEspR blocking antibodies (mAbs) with different epitopes, and a humanized anti-DEspR recombinant mAb cross-reactive in rodents and humans, to test DEspR inhibition effects. We measured DEspR-inhibition efficacy on multiple prometastatic CSC-functions in vitro, and on tumorigenesis and overall survival in a CSC-derived xenograft (CDX) nude rat model of PPC with comorbidities.

Results

Here we show that DEspR, a stress-survival receptor, is present on subsets of PDAC Panc1-TCs, TC-derived CSCs, and CSC-differentiated TCs (cscTCs), and that DESpR-inhibition decreases apoptosis-resistance and pro-metastatic mesenchymal functions of CSCs and cscTCs in vitro. We resolve the DNA-sequence/protein-function discordance by confirming ADAR1-RNA editing-dependent DEspR-protein expression in Panc1 and MiaPaCa2 TCs. To advance DEspR-inhibition as a nodal therapeutic approach for PPC, we developed and show improved functionality of a recombinant, humanized anti-DEspR IgG4S228P antibody, hu-6g8, over murine precursor anti-DEspR mabs. Hu-6g8 internalizes and translocates to the nucleus colocalized with cyto-nuclear shuttling galectins-1/3, and induces apoptotic cell changes. DEspR-inhibition blocks transperitoneal dissemination and progression to peritoneal carcinomatosis of heterogeneous DEspR±/CD133 ± Panc1-derived CSCs in xenografted nude rats, improving mOS without chemotherapy-like adverse effects. Lastly, we show DEspR expression in Stage II-IV primary and invasive TCs in the stroma in PDAC-patient tumor arrays.

Conclusion

Collectively, the data support humanized anti-DEspR hu-6g8 as a potential targeted antibody-therapeutic with promising efficacy, safety and prevalence profiles for PPC patients.
Prevalence of and factors associated with acute withdrawal symptoms after 24 weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study
Authors: Inoue Yuichi , Takaesu Yoshikazu , Koebis Michinori
Published: April 2021

Background

Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear.

Methods

In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses.

Results

Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105–2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245).

Conclusions

Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms.

Trial registration

UMIN000024462 (18/10/2016).
A National Survey of postgraduate physician assistant fellowship and residency programs
Authors: Kidd Vasco Deon , Vanderlinden Sarah , Hooker Roderick S.
Published: April 2021

Introduction

The development of postgraduate programs for physician assistants (PAs) began in 1973 and by 2020 there were approximately 72 programs spread across a broad range of medical and surgical disciplines. PA Post-graduate education programs are voluntary and available to American licensed PAs. Therefore, an assessment of the characteristics of PA post-graduate fellowships and residencies programs was initiated.

Method

A non-experimental, descriptive research study was designed to obtain information on the characteristics of PA postgraduate education programs in the US. The source of information was from surveyed members of the Association of Postgraduate Physician Assistant Programs (APPAP). Questions were drawn from consensus discussions. Directors of postgraduate programs that were operational in 2020 were eligible to participate.

Results

Seventy-two postgraduate program directors were invited to the survey and 34 program directors replied. These programs are geographically distributed across the US in 13 states. The respondents represent a wide range of medicine: surgery, emergency medicine, critical care, orthopaedics, hospitalist, psychiatry, oncology, primary care, pediatrics, and cardiology. Most programs are associated with an academic medical center and some institutions have more than one postgraduate specialty track. The curriculum includes bedside teaching, lectures, mentorship, assigned reading, procedures, simulation, and conferences. An average program length is 12 months and awards a certificate. Stipends for PA fellows are $50,000–80,000 (2020 dollars) and benefits include paid time off, health and liability insurance. About half of the programs bill for the services rendered by the PA. Over 90% of graduates are employed within 2 months of completing a PA postgraduate training program.

Conclusion

A trend is underway in American medicine to include PAs in postgraduate education. PA postgraduate training occurs across a broad spectrum of medical and surgical areas, as well as diverse institutions and organizations overseeing these programs. Most PA postgraduate programs are in teaching hospitals where the PA resident or PA fellow also serves as a house officer alongside a categorical resident. This study sets the stage for more granular economic and social research on this growing phenomenon in American medicine.
The impact of COVID-19 pandemic on training and mental health of residents: a cross-sectional study
Authors: Alshdaifat Eman , Sindiani Amer , Khasawneh Wasim , Abu-Azzam Omar , Qarqash Aref , Abushukair Hassan , Obeidat Nail
Published: April 2021

Background

Residency programs have been impacted by the Coronavirus disease 2019 (COVID-19) pandemic. In this study we aim to investigate and evaluate the impact of the pandemic on residents as well as residency training programs.

Methods

This was a cross-sectional study including a survey of 43 questions prepared on Google forms and electronically distributed among a convenience sample of residents training at a tertiary center in North Jordan during the COVID-19 pandemic. Data were collected in the period between October 30th and November 8th of 2020. The survey included questions that addressed the impact of the pandemic on residents’ health as well as training programs. The study participants included residents in training at KAUH in 2020 and were stratified according to the type of residency program (surgical residents (SRs) and non-surgical residents (NSRs)). Statistical methods included descriptive analysis, Chi-square or Fisher’s exact test, Mann Whitney U test, and Cramer’s V and r statistics as measures of effect sizes.

Results

Of all 430 residents, 255 (59%) responded to the survey. A total of 17 (7%) of residents reported being infected with COVID-19 and a significant difference was reported between SRs and NSRs (10% vs 4%, V = .124 “small effect” (95% CI; .017–.229),p = 0.048). Approximately, 106 (42%) reported a decrease in the number of staff working at the clinic and 164 (64%) reported limited access to personal protective equipment during the pandemic. On a 4-point Likert scale for the feeling of anxiety, the median was 2 (2–3 IQR) in the NSRs group, vs 2 (1–2 IQR) in the SRs groups, with the NSRs being more likely to feel anxious (r = 0.13 “small effect” (95% CI; 0.007–0.249),p = .044). Similarly, the proportion of residents who reported feeling anxious about an inadequacy of protective equipment in the work area was significantly greater in the NSRs group (90.3% vs 75.2%; V = .201 “small effect” (95% CI; .078–.313),p = .001), as well as the proportion of residents who reported feeling increased stress and anxiety between colleagues being also significantly higher in the NSRs group (88.1% vs 76%; V = .158 “small effect” (95% CI; .032–.279),p = .012).

Conclusion

The burden of the ongoing pandemic on the mental health status of residents is very alarming and so providing residents with psychological counseling and support is needed. Also, critical implications on the flow of residency training programs have been noticed. This necessitates adapting and adopting smart educational techniques to compensate for such limitations.
Patients’ perspectives on factors facilitating adherence to tuberculosis treatment in Iquitos, Peru: a qualitative study
Authors: Anthoney James , De Wildt Gilles , Meza Graciela , Skelton John , Newell Ian
Published: April 2021

Background

Tuberculosis is a major global health problem and one of the greatest barriers to its control is poor adherence to treatment. Peru has one of the highest burdens of TB in South America, with an incidence rate of 123 per 100,000 populations. There is currently a lack of evidence in South America about factors that facilitate adherence to treatment, with most previous research focusing on factors that negatively influence adherence to TB treatment.

Setting

This study was conducted in Iquitos, the capital city of the Loreto region, north-eastern Peru. Loreto has a high incidence of tuberculosis, estimated at 99 per 100,000 population, and a high poverty rate.

Methods

Twenty face-to-face, semi-structured interviews were conducted at two healthcare centres. Data collected from the interviews was analysed using thematic content analysis.

Results

Three main themes emerged from the data set. Personal Qualities, such as responsibility and determination, were perceived as important factors facilitating adherence. Participants described their Trust in Healthcare Providers positively, particularly focusing on their trust in clinical staff, although knowledge of tuberculosis and its treatment was limited. Social Support, from a variety of sources, was also seen as a driving factor for continued adherence.

Conclusions

The results suggest that more emphasis should be placed on educating tuberculosis patients about their disease and its treatment. Additionally, consideration should be given to improving the social support available to patients, for example with tuberculosis support groups involving ‘expert’ tuberculosis patients.
Factors related to large bone defects of bipolar lesions and a high number of instability episodes with anterior glenohumeral instability
Authors: Matsumura Noboru , Kaneda Kazuya , Oki Satoshi , Kimura Hiroo , Suzuki Taku , Iwamoto Takuji , Matsumoto Morio , Nakamura Masaya , Nagura Takeo
Published: April 2021

Background

Significant bone defects are associated with poor clinical results after surgical stabilization in cases of glenohumeral instability. Although multiple factors are thought to adversely affect enlargement of bipolar bone loss and increased shoulder instability, these factors have not been sufficiently evaluated. The purpose of this study was to identify the factors related to greater bone defects and a higher number of instability episodes in patients with glenohumeral instability.

Methods

A total of 120 consecutive patients with symptomatic unilateral instability of the glenohumeral joint were retrospectively reviewed. Three-dimensional surface-rendered/registered models of bilateral glenoids and proximal humeri from computed tomography data were matched by software, and the volumes of bone defects identified in the glenoid and humeral head were assessed. After relationships between objective variables and explanatory variables were evaluated using bivariate analyses, factors related to large bone defects in the glenoid and humeral head and a high number of total instability episodes and self-irreducible dislocations greater than the respective 75th percentiles were evaluated using logistic regression analyses with significant variables on bivariate analyses.

Results

Larger humeral head defects (P< .001) and a higher number of total instability episodes (P= .032) were found to be factors related to large glenoid defects. On the other hand, male sex (P= .014), larger glenoid defects (P= .015), and larger number of self-irreducible dislocations (P= .027) were related to large humeral head bone defects. An increased number of total instability episodes was related to longer symptom duration (P= .001) and larger glenoid defects (P= .002), and an increased number of self-irreducible dislocations was related to larger humeral head defects (P= .007).

Conclusions

Whereas this study showed that bipolar lesions affect the amount of bone defects reciprocally, factors related to greater bone defects differed between the glenoid and the humeral head. Glenoid defects were related to the number of total instability episodes, whereas humeral head defects were related to the number of self-irreducible dislocations.
Elderly patients with concurrent hip fracture and lower respiratory tract infection: the pathogens and prognosis over different bedridden periods
Authors: Yuan Yuan , Tian Wei , Deng Xiaohui , Yue Rui , Ge Xiaozhu , Wu Xinbao , Zhang Ping
Published: April 2021

Background

Elderly patients who experience hip fractures often become bedridden and are at risk of developing lower respiratory tract infections. The current study was to investigate the etiology and bacterial drug resistance patterns of elderly patients with hip fractures and lower respiratory tract infections on prolonged bedridden time and to determine their prognosis.

Methods

Patients diagnosed with hip fractures admitted from May 2015 to April 2017 were included. The basic characteristics including the patients’ gender, age, fracture type, operation mode, bedridden duration, length of hospital stay, prognosis, past medical history, routine bloodwork, C-reactive protein (CRP), procalcitonin (PCT), blood biochemistry, blood gas analysis, glycosylated hemoglobin (HbA1C%), sputum smear, sputum culture, and anti-infection and related therapy were recorded. All patients were classified into three groups based on bed rest duration, including short-term (<1 month), mid-term (1–12 months), and long-term (> 12 months). The correlation between the bedridden time and the patients’ basic characteristics, disease history, laboratory examination results, pathogen, anti-infection, and related therapy were evaluated. The risk factors related to the prognosis of the disease were investigated.

Results

Prolonged bed rest in patients led to an increase in hospitalization time, mortality rates, and decreased serum albumin levels (P< 0.05). Sputum bacteriological culture results showed that, with bed rest prolongation, the proportion ofPseudomonas aeruginosaand fungal infections increased. Binomial logistic regression of pulmonary infection prognosis, glucocorticoid use during the anti-infective period, prolonged bedridden time, and serum albumin level showed that intravenous use of glucocorticoid during anti-infective treatment, bed rest > 1 year, and low serum albumin level were related to poor prognosis.

Conclusion

Elderly hip fracture patients with prolonged bedridden time had an increased chance of opportunistic pulmonary infection and decreased nutritional status. Glucocorticoids should be used cautiously.
MRI recovery of the Achilles tendon after percutaneous tenotomy in older children
Authors: Yao Manye , Zhang Chunxu , Cheng Weyland , Guo Junhong , Dong Shijie
Published: April 2021

Background

An observational study was conducted to evaluate the recovery of older children with relapsed congenital clubfoot who underwent an Achilles tenotomy for the second time as part of the Ponseti treatment.

Methods

Thirteen patients (19 feet) with congenital clubfoot underwent Achilles tenotomy where magnetic resonance images of the severed tendons were taken after 1, 3, and 6 weeks post-procedure. The participants were categorized into older children who underwent tenotomy for the first time (group A: mean, 4.9±1.8, and range, 2.8–7 years old) and older children who underwent tenotomy for a second time (group B: mean, 4.9±1.5, and range, 3–6.8 years old). The area of high signal intensity between the severed tendons on MRI scans was computed using Python programming language and compared with clinical assessment.

Results

Three weeks after Achilles tenotomy, groups A and B had clinically intact tendons in 9 out of 11 and 2 out of 8 feet, respectively, according to both clinical and MRI assessment. From week 1 to week 3 post-tenotomy, computational analysis showed that the mean high signal intensity area of group A decreased by 88.5±15.2%, which was significantly different (P .048 < .05) than the percent reduction of high signal intensity area of group B (69.0±24.9%).

Conclusion

Children who underwent Achilles tenotomy for the second time showed slower tendon recovery on the third week post-procedure. A possible reason for slower healing times may be due to the location of tenotomy in being further away from the musculotendinous junction where extrinsic healing mechanisms take place.
An adult with episodic retrosternal chest pain: an unusual presentation of congenital pulmonary airway malformation – case report
Authors: Goldsmith Ira , George Joseph , Aslam Umair , Sharma Sobaran
Published: April 2021

Background

Congenital pulmonary airway malformation (CPAM) with partial anomalous pulmonary venous connection presenting as episodic retrosternal chest pain on exertion in an adult has not been described.

Case presentation

A 21-year-old female, non-smoker, presented with a 4-year history of sharp, episodic, retrosternal chest pains brought on with exercise. A contrast-enhanced computed tomography (CT) scan showed a grossly overinflated left lower lobe with partial anomalous pulmonary venous drainage into the left hemi-azygos vein. Lobectomy, the recommended treatment of choice, carried out thoracoscopically, was curative with satisfactory mid-term results. Histology confirmed type-II congenital pulmonary airway malformation.

Conclusions

CPAM can present in young adults with unusual symptoms of chest pain on exertion. When suspected a contrast-enhanced CT scan is the gold standard for establishing the diagnosis. An anatomical lung resection is curative with satisfactory medium term results.
Towards enhanced understanding of idiopathic ketotic hypoglycemia: a literature review and introduction of the patient organization, Ketotic Hypoglycemia International
Authors: Drachmann Danielle , Hoffmann Erica , Carrigg Austin , Davis-Yates Beccie , Weaver Valerie , Thornton Paul , Weinstein David A. , Petersen Jacob S. , Shah Pratik , Christesen Henrik Thybo
Published: April 2021

Background

Idiopathic Ketotic hypoglycemia (IKH) is a diagnosis of exclusion. Although considered as the most frequent cause of hypoglycemia in childhood, little progress has been made to advance the understanding of IKH since the medical term was coined in 1964. We aimed to review the literature on ketotic hypoglycemia (KH) and introduce a novel patient organization, Ketotic Hypoglycemia International (KHI).

Results

IKH may be diagnosed after the exclusion of various metabolic and hormonal diseases with KH. Although often mild and self-limiting, more severe and long-lasting IKH occurs. We therefore divide IKH in physiological KH and pathological KH, the latter defined as recurrent symptomatic, or occasionally symptomatic, episodes with beta-hydroxybutyrate ≥ 1.0 mmol/L and blood glucose < 70 mg/dL (3.9 mol/L), in the absence of prolonged fasting, acute infections and chronic diseases known to cause KH. Pathological KH may represent undiscovered diseases, e.g. glycogen storage disease IXa, Silver–Russel syndrome, and ketone transporter defects, or suggested novel disease entities identified by exome sequencing. The management of KH aims to prevent hypoglycemia, fatty acid oxidation and protein deficiency by supplying adequate amounts of carbohydrates and protein, including nutritional therapy, uncooked cornstarch, and sometimes continuous tube feeding by night. Still, intravenous dextrose may be needed in acute KH episodes. Failure to acknowledge that IKH can be more than normal variation may lead to under-treatment. KHI is a non-profit, patient-centric, global organization established in 2020. The organization was created by adult IKH patients, patient family members, and volunteers. The mission of KHI is to enhance the understanding of IKH while advocating for patients, their families and the continued research into KH.

Conclusion

IKH is a heterogeneous disorder including physiological KH and pathological KH. IKH may represent missed diagnoses or novel disease entities, but shares common management principles to prevent fatty acid oxygenation. KHI, a novel patient organization, aims to enhance the understanding of IKH by supporting IKH families and research into IKH.
Lymphocyte expansion in bioreactors: upgrading adoptive cell therapy
Authors: Garcia-Aponte Oscar Fabian , Herwig Christoph , Kozma Bence
Published: April 2021

Bioreactors are essential tools for the development of efficient and high-quality cell therapy products. However, their application is far from full potential, holding several challenges when reconciling the complex biology of the cells to be expanded with the need for a manufacturing process that is able to control cell growth and functionality towards therapy affordability and opportunity. In this review, we discuss and compare current bioreactor technologies by performing a systematic analysis of the published data on automated lymphocyte expansion for adoptive cell therapy. We propose a set of requirements for bioreactor design and identify trends on the applicability of these technologies, highlighting the specific challenges and major advancements for each one of the current approaches of expansion along with the opportunities that lie in process intensification. We conclude on the necessity to develop targeted solutions specially tailored for the specific stimulation, supplementation and micro-environmental needs of lymphocytes’ cultures, and the benefit of applying knowledge-based tools for process control and predictability.
Monitoring advances including consent: learning from COVID-19 trials and other trials running in UKCRC registered clinical trials units during the pandemic
Authors: Love Sharon B. , Armstrong Emma , Bayliss Carrie , Boulter Melanie , Fox Lisa , Grumett Joanne , Rafferty Patricia , Temesi Barbara , Wills Krista , Corkhill Andrea
Published: April 2021

The COVID-19 pandemic has affected how clinical trials are managed, both within existing portfolios and for the rapidly developed COVID-19 trials. Sponsors or delegated organisations responsible for monitoring trials have needed to consider and implement alternative ways of working due to the national infection risk necessitating restricted movement of staff and public, reduced clinical staff resource as research staff moved to clinical areas, and amended working arrangements for sponsor and sponsor delegates as staff moved to working from home.

Organisations have often worked in isolation to fast track mitigations required for the conduct of clinical trials during the pandemic; this paper describes many of the learnings from a group of monitoring leads based in United Kingdom Clinical Research Collaboration (UKCRC) Clinical Trials Unit (CTUs) within the UK.

The UKCRC Monitoring Task and Finish Group, comprising monitoring leads from 9 CTUs, met repeatedly to identify how COVID-19 had affected clinical trial monitoring. Informed consent is included as a specific issue within this paper, as review of completed consent documentation is often required within trial monitoring plans (TMPs). Monitoring is defined as involving on-site monitoring, central monitoring or/and remote monitoring.

Monitoring, required to protect the safety of the patients and the integrity of the trial and ensure the protocol is followed, is often best done by a combination of central, remote and on-site monitoring. However, if on-site monitoring is not possible, workable solutions can be found using only central or central and remote monitoring. eConsent, consent by a third person, or via remote means is plausible. Minimising datasets to the critical data reduces workload for sites and CTU staff. Home working caused by COVID-19 has made electronic trial master files (TMFs) more inviting. Allowing sites to book and attend protocol training at a time convenient to them has been successful and worth pursuing for trials with many sites in the future.

The arrival of COVID-19 in the UK has forced consideration of and changes to how clinical trials are conducted in relation to monitoring. Some developed practices will be useful in other pandemics and others should be incorporated into regular use.
Efficacy of a spot-on formulation containing moxidectin 2.5%/imidacloprid 10% for the treatment of Cercopithifilaria spp. and Onchocerca lupi microfilariae in naturally infected dogs from Portugal
Authors: Otranto Domenico , Colella Vito , Bezerra-Santos Marcos Antônio , Mendoza-Roldan Jairo Alfonso , Cavalera Maria Alfonsa , Pereira André , Schaper Roland , Maia Carla
Published: April 2021

Background

Onchocerca lupi and Cercopithifilaria spp. are vector-borne filarioids of dogs, which harbour skin microfilariae (mfs), the former being of zoonotic concern. Proper treatment studies using compounds with microfilaricidal activity have not been performed. Therefore, this study aimed to assess the efficacy of a commercially available spot-on formulation containing moxidectin 2.5%/imidacloprid 10% for the treatment of O. lupi or Cercopithifilaria spp. skin-dwelling mfs in naturally infected dogs.

Methods

Privately owned dogs (n = 393) from southern Portugal were sampled via skin biopsies to identify and count mfs in 20 µl of skin sediment. A total of 22 mfs-positive dogs were allocated to treatment group (n = 11; G1) or left untreated as a control (n = 11; G2). As a pilot investigation to test the treatment efficacy, five dogs assigned to G1 were treated four times at monthly intervals with moxidectin 2.5%/imidacloprid 10% spot-on formulation on SDs 0, 28 (± 2), 56 (± 2), and 84 (± 2). Based on the negative results for both O. lupi and/or Cercopithifilaria spp. mfs of dogs in the pilot study from SD28 onwards, the remaining six dogs in G1 were treated at SD0 and assessed only at SD28.

Results

Of the 393 animals sampled, 78 (19.8%) scored positive for skin-dwelling mfs. At the pilot investigation, a mean number of 19.6 mfs for O. lupi was recorded among five infected dogs whereas no mfs were detected at SD28. At SD0, the mean number of Cercopithifilaria spp. larvae was 12.6 for G1 and 8.7 for G2. The mean number of mfs for G2 was 20.09.

Conclusions

Results herein obtained suggest that a single treatment with moxidectin 2.5%/imidacloprid 10% spot-on formulation is efficacious against skin-dwelling mfs in dogs. The microfilaricidal effect of moxidectin could also be useful in reducing the risk of O. lupi infection for humans.

Graphical Abstract
Decapneization as supportive therapy for the treatment of status asthmaticus: a case report
Authors: Esposito Rossella , Esposito Irene , Imperatore Francesco , Liguori Giovanni , Gritti Fabrizio , Cafora Chiara , Marsilia Paolo Francesco , De Cristofaro Maria
Published: April 2021

Background

Acute severe asthma is a life-threatening medical emergency. Characteristics of asthma include increased airway resistance and dynamic pulmonary hyperinflation that can manifest in dangerous levels of hypercapnia and acidosis, with significant mortality and morbidity. Severe respiratory distress can lead to endotracheal intubation followed by mechanical ventilation, which can cause increased air trapping with dynamic hyperinflation, predisposing the lungs to barotraumas.

Case presentation

The present case report describes the use of the minimally invasive ECCO2R ProLUNG® (Estor) with protective low-tidal-volume ventilation, in a Caucasian patient with near-fatal asthma and with no response to conventional therapy.

Conclusions

Since hypercarbia rather than hypoxemia is the primary abnormality in status asthmaticus, a rescue therapeutic strategy combining the ECCO2R membrane ProLUNG® (Estor) with ultra-protective low-tidal-volume ventilation can be successfully applied to limit the risk of severe barotrauma during invasive mechanical ventilation. ECCO2R ProLUNG® is a partial respiratory support technique that, based on the use of an extracorporeal circuit with a gas-exchange membrane, achieves relevant CO2 clearance directly from the blood using double-lumen venous-venous vascular access, at blood flow in the range of 0.4–1.0 L/minute.
Andrographolide promotes proliferative and osteogenic potentials of human placenta-derived mesenchymal stem cells through the activation of Wnt/β-catenin signaling
Authors: Phunikom Naruphong , Boonmuen Nittaya , Kheolamai Pakpoom , Suksen Kanoknetr , Manochantr Sirikul , Tantrawatpan Chairat , Tantikanlayaporn Duangrat
Published: April 2021

Introduction

The in vitro expansion and differentiation of mesenchymal stem cells derived from bone marrow (BM-hMSCs) are considered as potential therapeutic tools for clinical applications in bone tissue engineering and regenerative medicine. However, invasive sampling and reduction in number and proliferative capacity with age are the major limitations of BM-hMSCs. Recently, human placenta-derived MSCs (PL-hMSCs) obtained by a non-invasive procedure have attracted much interest. Attempts to increase the potential of PL-hMSCs would be an important paradigm in regenerative medicine. Herein, we examined the proliferative and osteogenic effect of andrographolide (AP) on PL-hMSCs.

Methods

Mesenchymal stem cells were isolated from full-term normal human placentas and were characterized before using. Cell cytotoxicity and proliferative effect of AP were examined by MTT and BrdU assay, respectively. The non-toxicity concentrations of AP were further assessed for osteogenic effect determined by alkaline phosphatase (ALP) expression and activity, alizarin red staining, and osteoblast-specific gene expressions. Screening of genes involved in osteogenic differentiation-related pathways modulated by AP was explored by a NanoString nCounter analysis.

Results

PL-hMSCs generated in this study met the MSC criteria set by the International Society of Cellular Therapy. The non-cytotoxic concentrations of AP on PL-hMSCs are up to 10 μM. The compound increased PL-hMSC proliferation concomitant with increases in Wnt/β-catenin level and activity. It also enhanced osteogenic differentiation in association with osteoblast-specific mRNA expression. Further, AP promoted bone formation and increased bone structural protein level, osteocalcin, in osteoblastic cells. Gene screening analysis showed the upregulation of genes related to Wnt/β-catenin, TGFβ/BMP, SMAD, and FGF signaling pathways.

Conclusion

We demonstrated, for the first time, the potential role of AP in promoting proliferation, osteogenic differentiation, and osteoblast bone formation of PL-hMSCs. This study suggests that AP may be an effective novel agent for the improvement of PL-hMSCs and stem cell-based therapy for bone regeneration.
Channel state information-based multi-dimensional parameter estimation for massive RF data in smart environments
Authors: Yang Xiaolong , She Yuan , Xie Liangbo , Li Zhaoyu
Published: April 2021

Smart environment sensing and other applications play a more and more important role along with the rapid growth of device-free sensing-based services, and extracting parameters contained in channel state information (CSI) accurately is the basis of these applications. However, antenna arrays in wireless devices are all planar arrays whose antenna spacing does not meet the spatial sampling theorem while the existing parameter estimation methods are almost based on the array satisfying the spatial sampling theorem. In this paper, we propose a parameter estimation algorithm to estimate the signal parameters of angle of arrival (AoA), time of flight (ToF), and Doppler frequency shift (DFS) based on the service antenna array, which does not satisfy the spatial sampling theorem. Firstly, the service antenna array is mapped to a virtual linear array and the array manifold of the virtual linear array is calculated. Secondly, the virtual linear array is applied to estimate the multi-dimensional parameters of the signal. Finally, by calculating the geometric relationship between the service antenna and the virtual linear array, the parameters of the signal incident on the service antenna can be obtained. Therefore, the service antenna can not only use the communication channel for information communication, but also sense the surrounding environment and provide related remote sensing and other wireless sensing application services. Simulation results show that the proposed parameter estimation algorithm can accurately estimate the signal parameters when the array antenna spacing does not meet the spatial sampling theorem. Compared with TWPalo, the proposed algorithm can estimate AoA within 3∘, while the error of ToF and DFS parameter estimation is within 1 ns and 1 m/s.
Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection
Authors: Mu Andre , McDonald Daniel , Jarmusch Alan K. , Martino Cameron , Brennan Caitriona , Bryant Mackenzie , Humphrey Gregory C. , Toronczak Julia , Schwartz Tara , Nguyen Dominic , Ackermann Gail , D’Onofrio Anthony , Strathdee Steffanie A. , Schooley Robert T. , Dorrestein Pieter C. , Knight Rob , Aslam Saima
Published: April 2021

Background

Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood.

Results

Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum.

Conclusion

Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections.
Novel targetable FGFR2 and FGFR3 alterations in glioblastoma associate with aggressive phenotype and distinct gene expression programs
Authors: Georgescu Maria-Magdalena , Islam Mohammad Zahidul , Li Yan , Traylor James , Nanda Anil
Published: April 2021

Prognostic molecular subgrouping of glioblastoma is an ongoing effort and the current classification includes IDH-wild-type and IDH-mutant entities, the latter showing significantly better prognosis. We performed a comparative integrated analysis of the FGFR glioblastoma subgroup consisting of 5 cases from a prospective 101-patient-cohort. FGFR alterations includedFGFR2-TACC2andFGFR2amplifications arising in a multifocal IDH-mutant glioblastoma with unexpected 2.5-month patient survival, novelFGFR3carboxy-terminal duplication andFGFR3-TLN1fusion, and two previously describedFGFR3-TACC3fusions. The FGFR2 tumors showed additional mutations inSERPINE1/PAI-1 andMMP16, as part of extensive extracellular matrix remodeling programs. Whole transcriptomic analysis revealed common proliferation but distinct morphogenetic gene expression programs that correlated with tumor histology. The kinase program revealedEPHA3,LTKandALKreceptor tyrosine kinase overexpression in individual FGFR tumors. Paradoxically, all FGFR-fused glioblastomas shared strong PI3K and MAPK pathway suppression effected bySPRY,DUSPandAKAP12inhibitors, whereas theFGFR2-TACC2tumor elicited also EGFR suppression byERRFI1upregulation. This integrated analysis outlined the proliferation and morphogenetic expression programs in FGFR glioblastoma, and identified four novel, clinically targetable FGFR2 and FGFR3 alterations that confer aggressive phenotype and trigger canonical pathway feedback inhibition, with important therapeutic implications.
Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington’s disease
Authors: Zhou Ya , Peskett Thomas R. , Landles Christian , Warner John B. , Sathasivam Kirupa , Smith Edward J. , Chen Shu , Wetzel Ronald , Lashuel Hilal A. , Bates Gillian P. , Saibil Helen R.
Published: April 2021

Huntington’s disease (HD) is a late onset, inherited neurodegenerative disorder for which early pathogenic events remain poorly understood. Here we show that mutant exon 1 HTT proteins are recruited to a subset of cytoplasmic aggregates in the cell bodies of neurons in brain sections from presymptomatic HD, but not wild-type, mice. This occurred in a disease stage and polyglutamine-length dependent manner. We successfully adapted a high-resolution correlative light and electron microscopy methodology, originally developed for mammalian and yeast cells, to allow us to correlate light microscopy and electron microscopy images on the same brain section within an accuracy of 100 nm. Using this approach, we identified these recruitment sites as single membrane bound, vesicle-rich endolysosomal organelles, specifically as (1) multivesicular bodies (MVBs), or amphisomes and (2) autolysosomes or residual bodies. The organelles were often found in close-proximity to phagophore-like structures. Immunogold labeling localized mutant HTT to non-fibrillar, electron lucent structures within the lumen of these organelles. In presymptomatic HD, the recruitment organelles were predominantly MVBs/amphisomes, whereas in late-stage HD, there were more autolysosomes or residual bodies. Electron tomograms indicated the fusion of small vesicles with the vacuole within the lumen, suggesting that MVBs develop into residual bodies. We found that markers of MVB-related exocytosis were depleted in presymptomatic mice and throughout the disease course. This suggests that endolysosomal homeostasis has moved away from exocytosis toward lysosome fusion and degradation, in response to the need to clear the chronically aggregating mutant HTT protein, and that this occurs at an early stage in HD pathogenesis.
NaCl-related weathering of stone: the importance of kinetics and salt mixtures in environmental risk assessment
Authors: Godts Sebastiaan , Orr Scott Allan , Desarnaud Julie , Steiger Michael , Wilhelm Katrin , De Clercq Hilde , Cnudde Veerle , De Kock Tim
Published: April 2021

Salt weathering is one of the most important causes of deterioration in the built environment. Two crucial aspects need further investigation to understand the processes and find suitable measures: the impact of different climatic environments and the properties of salt mixture crystallization. We demonstrate the importance of kinetics in quantifying crystallization and dissolution cycles by combining droplet and capillary laboratory experiments with climate data analysis. The results proved that dissolution times for pure NaCl are typically slower than crystallization, while thermodynamic modelling showed a lower RHeq of NaCl (65.5%) in a salt mixture (commonly found in the built heritage) compared to its RHeq as a single salt (75.5%). Following the results, a minimum time of 30 min is considered for dissolution and the two main RHeq thresholds could be applied to climate data analysis. The predicted number of dissolution/crystallization cycles was significantly dependent on the measurement frequency (or equivalent averaging period) of the climatic data. An analysis of corresponding rural and urban climate demonstrated the impact of spatial phenomena (such as the urban heat island) on the predicted frequency cycles. The findings are fundamental to improve appropriate timescale windows that can be applied to climate data and to illustrate a methodology to quantify salt crystallization cycles in realistic environments as a risk assessment procedure. The results are the basis for future work to improve the accuracy of salt risk assessment by including the kinetics of salt mixtures.
Correlation between the cracking pattern of historical structure and soil properties: the case of the church in Kożuchów
Authors: Raszczuk Krzysztof , Karolak Anna
Published: April 2021

The paper presents a diagnosis of damage to heritage structures based on the case of the historic church in Kożuchów. The Church of the Purification of the Blessed Virgin Mary dates back to the thirteenth century and is an important sacral building in south-west Poland. Renovation and strengthening works have been conducted in recent years with the goal of structurally stabilizing the heritage building. The paper includes a short history of the building, as well as a review of contemporary diagnostic methods used in heritage buildings with emphasis on the methods used in the diagnosis of the discussed object. Correct diagnosis of the heritage building is the key to selecting an optimal design solution for supporting and strengthening the building structure. Pre-design analysis was based on a geotechnical assessment of ground conditions, identifying cracking patterns of walls and vaults, preparing a digital model using Heritage—Building Information Modeling technology and performing structural analysis. The main cause of cracking of the walls and vaults of the church is related to uneven subsidence and localized stability loss of the building’s foundations, resulting from differentiated soil and water conditions beneath the building. Based on the research and analysis, final conclusions and proposals for strengthening the structure were presented, including jet-grouting columns, tie rods and Fibre Reinforced Cementitious Matrix systems.
Surface energetics to assess influence of biomass-type and biomass–adsorbent interactions in expanded beds
Authors: Yelemane Vikas , Kangwa Martin , Dsouza Roy N. , Fernández-Lahore Marcelo
Published: April 2021

In integrated bioprocessing applications, expanded bed adsorption (EBA) chromatography presents an opportunity to harvest biomolecules directly from the crude feedstock. However, unfavorable biomass interactions with adsorbent usually leads to fouling, which reduces its protein binding capacity as it alters column hydrodynamics and binding site availability. In this work, a detailed study on biomass adhesion behavior of four different industrially relevant microorganisms on 26 different, most commonly occurring adsorbent surfaces with varying degrees of surface energy and surface charge has been conducted. The results showed the derivation of a relative “stickiness” factor for every microorganism, which further classifies each organism based on their general degree of adhesion to surfaces with respect to one another. The obtained results can help to better understand the effect of biomass homogenization on biomass–adsorbent interactions in EBA. The data of surface energy and charge for the surfaces investigated in this work can be used to calculate the stickiness factor of other microorganisms of interest and may assist in the development of novel adsorbent materials for EBA chromatography.