bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult-onset neuronal intranuclear inclusion disease, with both stroke-like onset and encephalitic attacks: a case report
Authors: Huang Ying , Jin Ge , Zhan Qun-ling , Tian Yun , Shen Lu
Published: March 2021

Background

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, the clinical manifestations of which are complex and easily misdiagnosed. NIID clinical characteristics are varied, affecting the central and peripheral nervous systems and autonomic nerves. In this study, we present an NIID case with both stroke-like onset and encephalitic attacks, which is a rare case report.

Case presentation

A 68-year-old Chinese female presented with sudden aphasia and limb hemiplegia as the first symptoms, as well as fever, cognitive impairment and mental irritability from encephalitic attacks. During hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity from diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. Electrophysiological tests revealed the main site of injury was at the myelin sheath in the motor nerves. A skin biopsy revealed eosinophilic spherical inclusion bodies in the nuclei of small sweat gland cells, fibroblasts and fat cells, whilst immunohistochemistry revealed that p62 and ubiquitin antibodies were positive. From genetic analyses, the patient was not a carrier of the fragile X mental retardation 1 (FMR1) permutation, but repeated GGC sequences in the NOTCH2NLC gene confirmed an NIID diagnosis. Through antipsychotic and nutritional support therapy, the patient’s symptoms were completely relieved within 3 weeks.

Conclusions

This report of an NIID case with both stroke-like onset and encephalitic attacks provides new information for NIID diagnoses, and a comprehensive classification of clinical characteristics.
PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma
Authors: Kim Sang Kyum , Kim Jee Hung , Kim Seung Hyun , Lee Young Han , Han Jung Woo , Baek Wooyeol , Woo Ha Young , Jeon Min Kyung , Kim Hyo Song
Published: March 2021

Background

Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy.

Methods

Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%.

Results

Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8–5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1–9% (n = 3, 4.5%), 10–49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45–5.56, P = 0.006).

Conclusion

We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.
Priorities for intervention to prevent diarrhea among children aged 0–23 months in northeastern Ethiopia: a matched case-control study
Authors: Baye Alemwork , Adane Metadel , Sisay Tadesse , Hailemeskel Habtamu Shimels
Published: March 2021

Background

The global public health problem of diarrhea is most prevalent in developing countries including Ethiopia, especially among children under two years of age. Limited information on the determinants of diarrhea among children aged 0–23 months hinders the design and prioritization of intervention strategies to address childhood diarrhea in Dessie City, northeastern Ethiopia. Therefore, this study was designed to assess the determinants of diarrhea in order to identify priority interventions for its control.

Methods

A community-based matched case-control study was conducted among children aged 0–23 months during January–February 2018. Cases defined as children with acute diarrhea, and controls defined as children without acute diarrhea, were matched by child’s age (months) and place of residence (residing in the same kebele, the lowest local administrative unit, each of which has a population of approximately 5000) during the two weeks prior to data collection. Data were collected from mothers/caregivers of the 119 cases and 238 matched controls using a pre-tested structured questionnaire and an observational checklist. Data were analyzed using conditional logistic regression model with 95% confidence interval (CI); variables with p < 0.05 from multivariable analysis were considered as significantly associated with acute diarrhea among children aged 0–23 months.

Results

Age of mothers/caregivers (> 35 years of age) (adjusted matched odds ratio [adjusted mOR] = 2.00; 95% CI: 1.37–5.8); divorced/widowed marital status (adjusted mOR = 1.40; 95% CI: 1.26–3.3); lack of exclusive breastfeeding (adjusted mOR = 2.12; 95% CI: 1.15–3.70); presence of feces within/around latrines (adjusted mOR = 1.37; 95% CI: 1.21–3.50); lack of handwashing facility near latrine (adjusted mOR = 1.50; 95% CI: 1.30–5.30); presence of domestic sewage discharge within and/or outside the compound (adjusted mOR = 3.29; 95% CI: 1.85–7.50) and practice of handwashing at fewer than three of the five critical daily times (adjusted mOR = 4.50; 95% CI: 2.54–9.50) were significantly associated with acute diarrhea among children aged under two years.

Conclusion

To reduce acute diarrheal disease among children under two, priority should be given to interventions that focus on improving exclusive breastfeeding practices, regular cleaning of latrines, advocating for availability of handwashing facility within/around latrines, use of proper domestic sewage discharge methods and improving handwashing practice at the five critical times each day. Strengthening communication that promotes hygiene and behavioural change may also raise awareness among mothers/caregivers and empower them to enhance handwashing practices at critical times.
Trend dynamics of thyroid cancer incidence among China and the U.S. adult population from 1990 to 2017: a joinpoint and age-period-cohort analysis
Authors: Cui Yiran , Mubarik Sumaira , Li Ruijia , Nawsherwan  , Yu Chuanhua
Published: March 2021

Background

Thyroid cancer (TC) is the most common malignant disease of the endocrine system. Based on the previously published reports, the incidence of TC has been increasing in the past 25 years, and the reason for the increase is not yet clear. The present study aims to reveal the long-term trends and age–period–cohort effects for the incidence of TC in China and the U.S. from 1990 to 2017.

Methods

We examined the trends of TC incidence and the average annual percentage change (AAPC) of rate using the Joinpoint regression analysis in the two countries, for the different genders (men/women) in the Global Burden of Disease (GBD 2017). We further used an age-period-cohort model to analyze age-period-cohort effects on TC incidence.

Results

The ASIR of China increased markedly with AAPC of 4.5% (95% confidence interval (CI): 4.0, 5.0%) and 1.8% (1.6, 2.0%) for men and women during 1990–2017. The ASIR of the U. S increased by 1.4% (1.0, 1.8%) and 1.3% (0.9, 1.7%) for men and women from 1990 to 2017.TC increased with the age and period. Aging was one of the most influential factors of TC in China. The age effect increased markedly in the U.S. compared with China. The period effect showed an increase in China while that tended to grow steadily during 1990–2017 in the U.S. The cohort effect peaked in 1963–1967 birth cohorts for men and women in China and declined consistently in the birth cohort in the U.S.

Conclusion

From 1990 to 2017, due to ionizing radiation and over-diagnosis, age-standardized TC incidence rates in both genders rose in China and the U.S. The standardized incidence rate of women is higher than that of men. It is necessary to provide women with reasonable prevention and protection measures for TC. We need to apply for health services and screening to reduce ionizing radiation.
Influence of scaler tip design on root surface roughness, tooth substance loss and patients’ pain perception: an in vitro and a randomised clinical trial
Authors: Abdul Hayei Nur Ayman , Yahya Noor Azlin , Safii Syarida Hasnur , Saub Roslan , Vaithilingam Rathna Devi , Baharuddin Nor Adinar
Published: March 2021

Background

The influence of scaler tip design on root surface roughness, tooth substance loss and patients’ pain perception is investigated.

Methods

This article was divided into the following parts: Part 1 Surface roughness and substance loss: an in vitro study, which involves intact extracted teeth sectioned and treated using a piezoelectric ultrasonic device (PM200 EMS Piezon, Switzerland) with a conventional scaler tip (FS-407) and a Perio Slim (PS) scaler tip (Perio Slim DS-016A). All sectioned samples for tooth surface roughness (n = 20) and tooth substance loss (n = 46) analyses were measured and compared using a 3D surface texture analyser and scanning electron microscope (SEM) respectively, at baseline and following scaling. Part 2 Pain Perception: a clinical study, which was a split mouth study design including 30 participants with gingivitis and/or mild chronic periodontitis; treated with supra-gingival scaling from teeth #13 to #23. Subjects were randomised to group A or group B. Group A was treated first with PS scaler tips, whereas group B was treated first with conventional scaler tips. Pain perception was recorded using the visual analogue scale (VAS).

Results

In vitro study: both scaler tips caused significant reduction in root substance roughness after scaling (p < 0.05), but no significant difference between the two scaler tips (p > 0.05) was observed. The PS scaler tip caused statistically significantly less root substance loss (p < 0.05) when the initial thickness of the tooth was < 1000 µm. Clinical study: the participants reported significantly lesser pain score during scaling using the PS scaler tip (median: 3) than when using the conventional scaler tip (median: 5) (p < 0.05).

Conclusions

In the in vitro study, using a slim scaler tip design causes less tooth substance loss compared to a wider scaler tip design. In the clinical study, less pain was observed compared than a wide (conventional) scaler tip design.
Recurrence characteristics and clinicopathological results of borderline ovarian tumors
Authors: Niu Lina , Tian Huihui , Xu Yongjun , Cao Jieqiong , Zhang Xu , Zhang Junli , Hou Jiajia , Lv Weiqin , Wang Junxia , Xin Li , Dong XuFeng , Xu Tao , Nan Yuan , Wei Hua , Chai Xinting , Li Na , Ni Yan , Shang Yun , Zhang Lizhen , Zhao Ye
Published: March 2021

Background

This study aimed to investigate the clinical and pathological characteristics, and the recurrence and prognostic factors of borderline ovarian tumors (BOTs).

Methods

The data of 286 patients admitted to hospital and followed up for more than ten months were analyzed retrospectively to study the clinicopathological characteristics and related factors of recurrence.

Results

The median age of the patients was 42.06 ± 14.97 years, and the duration of the follow-up ranged from 10–109 months. During the follow-up period, 40 patients had a recurrence. Of these patients, 36 were ≤ 40 years, and patients with premenopausal recurrence accounted for 20.5% (36/176). In patients undergoing conservative treatment or radical operations, the recurrence rates were 21.3% and 1.8%, respectively, and they were 13.4% (36/268) in patients at Federation International of Gynecology and Obstetrics (FIGO) stage I, and 22.2% (4/18) in patients at an advanced stage. Postoperative pathology revealed that 40 patients had micropapillary tumors, among whom ten patients (25%) had a recurrence, and 19 patients had complications with interstitial infiltration. Of these 19 patients, six had a recurrence (31.5%). Another 22 patients had complications with calcified sand bodies; among these, eight patients (36.4%) had a recurrence. All the differences were statistically significant (P < 0.05). There were four cancer-related deaths during the follow-up period. Late FIGO stage, conservative operation, and a high level of carbohydrate antigen 125 (CA125) were independent risk factors for the recurrence of BOTs.

Conclusion

BOTs usually occur in women under 40 years, have an occult onset, and half of the patients have no obvious clinical manifestations. Serum CA125 level can be used as a tumor marker to detect BOTs and the risk of its recurrence. Operation mode and FIGO stage are important independent factors for the recurrence of BOTs.
Prehospital emergency medical technicians can perform ultrasonography and blood analysis in prehospital evaluation of patients with chronic obstructive pulmonary disease: a feasibility study
Authors: Nadim Giti , Laursen Christian B. , Pietersen Pia I. , Wittrock Daniel , Sørensen Michael K. , Nielsen Lars B. , Rasmussen Claus-Henrik , Christensen Helle Marie , Helmerik Simon , Jørgensen Gitte , Titlestad Ingrid L. , Lassen Annmarie T. , Mikkelsen Søren
Published: March 2021

Introduction

Crowding of the emergency departments is an increasing problem. Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are often treated in the emergency departments for a very short period before discharged to their homes. It is possible that this treatment could take place in the patients’ homes with sufficient diagnostics supporting the treatment.

In an effort to keep the diagnostics and treatment of some of these patients in their homes and thus to reduce the patient load at the emergency departments, we implemented a prehospital treat-and-release strategy based on ultrasonography and blood testing performed by emergency medical technicians (EMT) or paramedics (PM) in patients with acute exacerbation of COPD.

Method

EMTs and PMs were enrolled in a six-hour educational program covering ultrasonography of the lungs and point of care blood tests. During the seasonal peak of COPD exacerbations (October 2018 – May 2019) all patients who were treated by the ambulance crews for respiratory insufficiency were screened in the ambulances. If the patient had uncomplicated COPD not requiring immediate transport to the hospital, ultrasonographic examination of the lungs, measurements of C-reactive protein and venous blood gases analyses were performed. The response to the initial treatment and the results obtained were discussed via telemedical consultation with a prehospital anaesthesiologist who then decided to either release the patient at the scene or to have the patient transported to the hospital. The primary outcome was strategy feasibility.

Results

We included 100 EMTs and PMs in the study. During the study period, 771 patients with respiratory insufficiency were screened. Uncomplicated COPD was rare as only 41patients were treated according to the treat-and-release strategy. Twenty of these patients (49%) were released at the scene. In further ten patients, technical problems were encountered hindering release at the scene.

Conclusion

In a few selected patients with suspected acute exacerbations of COPD, it was technically and organisationally feasible for EMTs and PMs to perform prehospital POCT-ultrasound and laboratory testing and release the patients following treatment. None of the patients released at the scene requested a secondary ambulance within the first 48 h following the intervention.
Study on supplemental test to improve the detection of bovine tuberculosis in individual animals and herds
Authors: Carneiro Paulo Alex Machado , de Moura Sousa Eliomar , Viana Rinaldo Batista , Monteiro Bruno Moura , do Socorro Lima Kzam Aline , de Souza Damazio Campos , Coelho Anderson Silva , Filho José Dantas Ribeiro , Jordao Ricardo Spacagna , Tavares Maria Regina Madruga , Kaneene John B.
Published: March 2021

Background

Bovine tuberculosis (bTB), is a worldwide disease caused by Mycobacterium bovis (M. bovis). The success of bTB eradication and control programs is based on early detection and the removal of reactors from a herd thus routine testing and cull strategy have been applied globally. Since the late nineteenth century, the Tuberculin Skin Test (TST) has been the primary antemortem test available to support bTB eradication campaigns. Due to the TST limitations in terms of Se and Sp, the credibility of the diagnosis is frequently questioned given the occurrence of false-positive and false-negative reactions, therefore, it is necessary to confirm reactive animals using other methods, ensuring the reliability of the diagnosis. The aim of this study was to evaluate the sensitivity and specificity of a multiplex enzyme-linked immunosorbent assay (ELISA) relative to the tuberculin test used for the diagnosis of tuberculosis in cattle in Brazil.

Results

Lack of agreement between comparative cervical tuberculin test and ELISA IDEXX TM was observed. The 2 animals positive on the comparative cervical tuberculin test did not react at the ELISA IDEXX TM and 22 negative reactors by comparative cervical tuberculin test were positive by the ELISA IDEXX TM. The ELISA IDEXX TM showed sensitivity that is significantly lower than the official screening test the single cervical tuberculin. ELISA IDEXX TM also detected infected animals and herds undetected by the comparative cervical tuberculin test. The parallel use of comparative cervical tuberculin test and ELISA IDEXX TM increased sensitivity and the feasibility bTB screening.

Conclusions

The results obtained here suggest that the ELISA IDEXX TM may be a supplemental test for the detection of Mycobacterium bovis infection in regions without routine testing and slaughter, where the disease generally progresses to more advanced stages and antibody responses are likely to be more prevalent. Evidence to support the validation of the ELISA IDEXX™ as a supplemental test for bTB eradication programs was provided.
Report from the CVOT Summit 2020: new cardiovascular and renal outcomes
Authors: Schnell Oliver , Cos Xavier , Cosentino Francesco , Forst Thomas , Giorgino Francesco , Heersprink Hiddo J. L. , Kosiborod Mikhail , Wanner Christoph , Standl Eberhard
Published: March 2021

The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.

The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 (http://www.cvot.org).
Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?
Authors: Ward Mark P. , E. Kane Laura , A. Norris Lucy , Mohamed Bashir M. , Kelly Tanya , Bates Mark , Clarke Andres , Brady Nathan , Martin Cara M. , Brooks Robert D. , Brooks Doug A. , Selemidis Stavros , Hanniffy Sean , Dixon Eric P. , A. O’Toole Sharon , J. O’Leary John
Published: March 2021

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.
Suicide attempt and its associated factors amongst women who were pregnant as adolescents in Bangladesh: a cross-sectional study
Authors: Li Jie , Imam Syeda Zerin , Jing Zhengyue , Wang Yi , Zhou Chengchao
Published: March 2021

Background

Adolescent pregnancy is a risk factor for suicide. We aimed to assess the prevalence of suicide attempts among young women with adolescent pregnancy in Bangladesh and to explore its associated factors.

Methods

In this cross-sectional study, we surveyed young women with adolescent pregnancy in urban and rural areas in Bangladesh to assess suicide attempts, socio-demographic and pregnancy-related characteristics, perceived health status, and perceived social support. Binary logistic regression analysis was conducted to explore the relationship between potentially related factors and suicide attempts.

Results

Of the participants, 6.5% (61/940) reported suicide attempts in the past 12 months, and the majority (88.5%) of the attempts happened within one year after the pregnancy. Participants with more years after first pregnancy (odds ratio (OR) = 0.47, 95% CI: 0.37–0.61) and more perceived social support from friends (OR = 0.69, 95% CI: 0.55–0.86) were less likely to have suicide attempts, and those perceived bad health status compared with good/fair health status (OR = 8.38, 95% CI: 3.08–22.76) were more likely to attempt suicide.

Conclusions

Women with adolescent pregnancy were at high risk of suicide attempts, especially those during the first postnatal year. The risk of suicide attempts attenuated with the time after pregnancy, and perceived social support from friends was a protective factor and perceived bad health status was a risk factor for suicide attempts among young women who have experienced adolescent pregnancy.
Serious adverse events and 30-day hospital readmission rate following elective total knee arthroplasty: a systematic review and meta-analysis
Authors: Papakostidis Costas , Giannoudis Peter V. , Watson J. Tracy , Zura Robert , Steen R. Grant
Published: March 2021

Background

Elective total knee arthroplasty (TKA) is a common surgery which has evolved rapidly. However, there are no recent large systematic reviews of serious adverse event (SAE) rate and 30-day readmission rate (30-dRR) or an indication of whether surgical methods have improved.

Methods

To obtain a pooled estimate of SAE rate and 30-dRR following TKA, we searched Medline, Web of Science, Cochrane Library, and Google Scholar databases. Data were extracted by two authors following PRISMA guidelines. Eligibility criteria were defined prior to a comprehensive search. Studies were eligible if they were published in 2007 or later, described sequelae of TKA with patient N > 1000, and the SAE or 30-dRR rate could be calculated. SAEs included return to operating room, death or coma, venous thromboembolism (VTE), deep infection or sepsis, myocardial infarction, heart failure or cardiac arrest, stroke or cerebrovascular accident, or pneumonia.

Results

Of 248 references reviewed, 28 are included, involving 10,153,503 patients; this includes 9,483,387 patients with primary TKA (pTKA), and 670,116 patients with revision TKA (rTKA). For pTKA, the SAE rate was 5.7% (95% CI 4.4−7.2%, I2 = 100%), and the 30-dRR was 4.8% (95% CI 4.3−5.4%, I2 = 100%). For rTKA, the SAE rate was 8.5% (95% CI 8.3−8.7%, I2 = 77%), while the 30-dRR was 7.2% (95% CI 6.4−8.0%, I2 = 81%). Odds of 30-dRR following pTKA were about half that of rTKA (OR 0.57, 95% CI 0.53−0.62%, p < 0.001, I2 = 45%). Of patients who received pTKA, the commonest SAEs were VTE (1.22%; 95% CI 0.83−1.70%) and genitourinary complications including renal insufficiency or renal failure (1.22%; 95% CI 0.83−1.67%). There has been significant improvement in SAE rate and 30-dRR since 2010 (χ2 test < 0.001).

Conclusions

TKA procedures have a relatively low complication rate, and there has been a significant improvement in SAE rate and 30-dRR over the past decade.
5-year results of a newly implemented mechanical circulatory support program for terminal heart failure patients in a Swiss non-cardiac transplant university hospital
Authors: Schaeffer Thibault , Pfister Otmar , Mork Constantin , Mohacsi Paul , Rueter Florian , Scheifele Simon , Morgen Anne , Zenklusen Urs , Doebele Thomas , Maurer Markus , Erb Joachim , Fassl Jens , Cueni Nadine , Siegemund Martin , Pargger Hans , Gahl Brigitta , Osswald Stefan , Eckstein Friedrich , Grapow Martin
Published: March 2021

Background

In Switzerland, long-term circulatory support programs have been limited to heart transplant centers. In 2014, to improve the management of patients with end-stage heart failure not eligible for transplantation, we implemented a left ventricular assist device (LVAD) program for destination therapy at the University Hospital of Basel.

Methods

We described the program set-up with practical aspects. Patients aged 65 and above with therapy refractory end-stage heart failure without major contraindication for LVAD implantation were included. Younger patients with bridge-to-candidacy profile were also considered. Using the Kaplan-Meier estimate, we retrospectively analyzed the overall survival and freedom from major adverse events after LVAD implantation. We compared our results to internationally reported data.

Results

Between October 2014 and September 2019, 16 patients received an LVAD in our center. The mean age at implantation was 67.1 years. The mean EuroSCORE II was 24.4% and the median INTERMACS level was 4. Thirteen patients received an LVAD as destination therapy and three patients as bridge-to-candidacy. The overall survival was 87.5 and 70% at 1 and 2 years, respectively. Freedom from stroke was 81.3% at 1 and 2 years. Freedom from device infection was 67.7 and 58.7% at 1 and 2 years, respectively. Freedom from gastrointestinal bleeding was 75 and 56.3% at 1 and 2 years, respectively. Freedom from readmission was 50 and 31.3% and at 6 months and 1 year, respectively.

Conclusions

The Basel experience demonstrated the possible implementation of an LVAD program for destination therapy or bridge-to-candidacy in a non-transplant comprehensive heart-failure center with midterm survival results and freedom from major adverse events comparable to international registries. Patient selection remains crucial.

Trial registration

This study was registered on the ClinicalTrials.gov database (NCT04263012).
Newborn screening for spinal muscular atrophy in Germany: clinical results after 2 years
Authors: Vill Katharina , Schwartz Oliver , Blaschek Astrid , Gläser Dieter , Nennstiel Uta , Wirth Brunhilde , Burggraf Siegfried , Röschinger Wulf , Becker Marc , Czibere Ludwig , Durner Jürgen , Eggermann Katja , Olgemöller Bernhard , Harms Erik , Schara Ulrike , Kölbel Heike , Müller-Felber Wolfgang
Published: March 2021

Background

Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was to assess the impact of genetic newborn screening for SMA on outcome.

Methods

We provided clinical data from 43 SMA patients, identified via polymerase chain reaction of the SMN1 gene from dried blood spots between January 2018 and January 2020 in Germany. Follow-up included neurophysiological examinations and standardized physiotherapeutic testing.

Results

Detection of SMA with newborn screening was consistent with known incidence in Germany. Birth prevalence was 1:6910; 39.5% had 2 SMN2 copies, 23% had 3 SMN2 copies, 32.5% had 4 copies, and 4.5% had 5 copies of the SMN2 gene. Treatment with SMA-specific medication could be started at the age of 14–39 days in 21 patients. Pre-symptomatically treated patients remained throughout asymptomatic within the observation period. 47% of patients with 2 SMN2 copies showed early, presumably intrauterine onset of disease. These patients reached motor milestones with delay; none of them developed respiratory symptoms. Untreated children with 2 SMN2 copies died. Untreated children with 3 SMN2 copies developed proximal weakness in their first year. In patients with ≥ 4 SMN2 copies, a follow-up strategy of “watchful waiting” was applied despite the fact that one of them was treated from the age of 6 months. Two infant siblings with 4 SMN2 copies were identified with a missed diagnosis of SMA type 3.

Conclusion

Identification of newborns with infantile SMA and prompt SMA-specific treatment substantially improves neurodevelopmental outcome, and we recommend implementation in the public newborn screening in countries where therapy is available. Electrophysiology is a relevant parameter to support the urgency of therapy. There has to be a short time interval between a positive screening result and referral to a therapy-ready specialized treatment center.
Complex emergencies and the control and elimination of neglected tropical diseases in Africa: developing a practical approach for implementing safe and effective mapping and intervention strategies
Authors: Kelly-Hope Louise A. , Sanders Angelia M. , Harding-Esch Emma , Willems Johan , Ahmed Fatima , Vincer Fiona , Hill Rebecca
Published: March 2021

Background

Complex emergencies resulting from conflict and political instability are a major challenge for national neglected tropical diseases (NTDs) control and elimination programmes, especially in sub-Saharan Africa. Currently, there are no formal guidelines for national programmes to use and plan activities in these humanitarian situations, therefore the aim of this study was to develop a new methodological approach for making decisions about the implementation of safe and effective mapping and mass drug administration (MDA) intervention strategies.

Methods

The study focussed on the 47 World Health Organization’s African Region (AFR) countries. NTD data were based on five diseases controlled by preventive chemotherapy (PC; i.e. lymphatic filariasis, onchocerciasis, schistosomiasis, soil transmitted helminths, trachoma), obtained from the WHO data portals and The Global Trachoma Atlas for 2018. Data on complex emergencies were obtained from the Armed Conflict Location and Event Data Project for 2018–2019.

NTD and conflict data were summarised and mapped. A decision tree was developed using NTD mapping, endemicity, MDA and implementing partners data, together with conflict status information at district level. South Sudan was used as a case study, given its current nexus of high NTD prevalence, incidences of conflict, and the presence of a national NTD programme and supporting partners.

Results

For the five NTDs, between 26 and 41 countries required PC, 69.2–212.7 million people were treated with coverage between 54.8–71.4%. In total 15,273 conflict events were reported including high rates of violence against civilians (29.4%), protests (28.8%), and battles (18.1%). The decision tree process included four main steps including i) information gathering ii) determine a disease mapping strategy iii) determine an MDA implementation strategy and iv) create a disease and conflict database. Based on these steps, risk maps were created. The South Sudan case study on onchocerciasis found the majority of the districts requiring mapping or MDA had a conflict event, and required specialised methods adapted to context and risk, with support from implementation partners in selected areas.

Conclusions

The paper presents a new methodological approach for implementing safe and effective mapping and intervention strategies in NTD endemic countries with ongoing complex emergencies, which will help to address challenges and make progress toward the NTD Roadmap targets of 2030.
Characterizing individuals accessing mental health services in the UAE: a focus on youth living in Dubai
Authors: Barbato Mariapaola , Al Hemeiri Shaikha , Nafie Shorouk , Dhuhair Baraa A. , Dabbagh Nadia T.
Published: March 2021

Background

Most mental health issues develop during adolescence, therefore identifying youth mental health needs and pathways to care is critical to improve prevention. To date, studies have typically focused on Western samples, while the impact of cultural diversity on perception of health and illness, and pathways to care, remain poorly understood. To address the shortage of studies conducted in the Arab world, and particularly in the United Arab Emirates (UAE), the present investigation aims to identify the characteristics of youth accessing mental health services in Dubai.

Methods

Data was collected retrospectively from patients’ records at Rashid Hospital Child Psychiatry Service. Information collected included demographics, life stressors, symptoms duration, main diagnosis, and presence/absence of psychotic features in patients’ symptomatology. The relationship between demographic and clinical variables was explored using Chi-square tests and negative binomial regression models.

Results

The sample included 99 treatment-seeking young patients (mean age 15.3; SD = 1.7); 47.5 % were Emirati (UAE national) and 52.5 % were non-Emirati patients. In our treatment-seeking youth sample Depressive disorders represented the most frequent diagnosis, followed by Bipolar and related disorders, Anxiety and stress related disorders, and Schizophrenia and psychotic disorders. Compared to Emirati patients, non-Emirati patients were more likely to report relationships with friends as a source of stress. Female help-seekers, compared to males, were more likely to report stressful relationships with family members, and to receive a diagnosis of Depressive disorders. The duration of symptoms before seeking help was significantly predicted by family stress, gender, self-harm behavior, a symptomatology with psychotic features, and a diagnosis of Anxiety disorders.

Conclusions

The present study contributes to characterizing youth accessing mental health services at Rashid Hospital’s Child Psychiatry service in Dubai. An overall prevalence of poor family functioning among help-seeking youth, and the importance of peer support for expatriate youth were highlighted. Gender differences in perceived stressors, diagnoses and help-seeking behavior suggest the need to promote help-seeking among young boys. While presentation with psychotic features seems to lead to quicker access to medical care, self-harm and anxiety appear to delay help-seeking. The potential implications of our results for promoting youth wellbeing in the region are discussed.
Prediction of short-term mortality in acute heart failure patients using minimal electronic health record data
Authors: Radhachandran Ashwath , Garikipati Anurag , Zelin Nicole S. , Pellegrini Emily , Ghandian Sina , Calvert Jacob , Hoffman Jana , Mao Qingqing , Das Ritankar
Published: March 2021

Background

Acute heart failure (AHF) is associated with significant morbidity and mortality. Effective patient risk stratification is essential to guiding hospitalization decisions and the clinical management of AHF. Clinical decision support systems can be used to improve predictions of mortality made in emergency care settings for the purpose of AHF risk stratification. In this study, several models for the prediction of seven-day mortality among AHF patients were developed by applying machine learning techniques to retrospective patient data from 236,275 total emergency department (ED) encounters, 1881 of which were considered positive for AHF and were used for model training and testing. The models used varying subsets of age, sex, vital signs, and laboratory values. Model performance was compared to the Emergency Heart Failure Mortality Risk Grade (EHMRG) model, a commonly used system for prediction of seven-day mortality in the ED with similar (or, in some cases, more extensive) inputs. Model performance was assessed in terms of area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity.

Results

When trained and tested on a large academic dataset, the best-performing model and EHMRG demonstrated test set AUROCs of 0.84 and 0.78, respectively, for prediction of seven-day mortality. Given only measurements of respiratory rate, temperature, mean arterial pressure, and FiO2, one model produced a test set AUROC of 0.83. Neither a logistic regression comparator nor a simple decision tree outperformed EHMRG.

Conclusions

A model using only the measurements of four clinical variables outperforms EHMRG in the prediction of seven-day mortality in AHF. With these inputs, the model could not be replaced by logistic regression or reduced to a simple decision tree without significant performance loss. In ED settings, this minimal-input risk stratification tool may assist clinicians in making critical decisions about patient disposition by providing early and accurate insights into individual patient’s risk profiles.
MITF induces escape from innate immunity in melanoma
Authors: Sánchez-del-Campo Luis , Martí-Díaz Román , Montenegro María F. , González-Guerrero Rebeca , Hernández-Caselles Trinidad , Martínez-Barba Enrique , Piñero-Madrona Antonio , Cabezas-Herrera Juan , Goding Colin R. , Rodríguez-López José Neptuno
Published: March 2021

Background

The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown.

Methods

By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing.

Results

Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance.

Conclusion

Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.
Trends in reasons for emergency calls during the COVID-19 crisis in the department of Gironde, France using artificial neural network for natural language classification
Authors: Gil-Jardiné Cédric , Chenais Gabrielle , Pradeau Catherine , Tentillier Eric , Revel Philippe , Combes Xavier , Galinski Michel , Tellier Eric , Lagarde Emmanuel
Published: March 2021

Objectives

During periods such as the COVID-19 crisis, there is a need for responsive public health surveillance indicators in order to monitor both the epidemic growth and potential public health consequences of preventative measures such as lockdown. We assessed whether the automatic classification of the content of calls to emergency medical communication centers could provide relevant and responsive indicators.

Methods

We retrieved all 796,209 free-text call reports from the emergency medical communication center of the Gironde department, France, between 2018 and 2020. We trained a natural language processing neural network model with a mixed unsupervised/supervised method to classify all reasons for calls in 2020. Validation and parameter adjustment were performed using a sample of 39,907 manually-coded free-text reports.

Results

The number of daily calls for flu-like symptoms began to increase from February 21, 2020 and reached an unprecedented level by February 28, 2020 and peaked on March 14, 2020, 3 days before lockdown. It was strongly correlated with daily emergency room admissions, with a delay of 14 days. Calls for chest pain and stress and anxiety, peaked 12 days later. Calls for malaises with loss of consciousness, non-voluntary injuries and alcohol intoxications sharply decreased, starting one month before lockdown. No noticeable trends in relation to lockdown was found for other groups of reasons including gastroenteritis and abdominal pain, stroke, suicide and self-harm, pregnancy and delivery problems.

Discussion

The first wave of the COVID-19 crisis came along with increased levels of stress and anxiety but no increase in alcohol intoxication and violence. As expected, call related to road traffic crashes sharply decreased. The sharp decrease in the number of calls for malaise was more surprising.

Conclusion

The content of calls to emergency medical communication centers is an efficient epidemiological surveillance data source that provides insights into the societal upheavals induced by a health crisis. The use of an automatic classification system using artificial intelligence makes it possible to free itself from the context that could influence a human coder, especially in a crisis situation. The COVID-19 crisis and/or lockdown induced deep modifications in the population health profile.
Disulfide bond engineering of AppA phytase for increased thermostability requires co-expression of protein disulfide isomerase in Pichia pastoris
Authors: Navone Laura , Vogl Thomas , Luangthongkam Pawarisa , Blinco Jo-Anne , Luna-Flores Carlos H. , Chen Xiaojing , von Hellens Juhani , Mahler Stephen , Speight Robert
Published: March 2021

Background

Phytases are widely used commercially as dietary supplements for swine and poultry to increase the digestibility of phytic acid. Enzyme development has focused on increasing thermostability to withstand the high temperatures during industrial steam pelleting. Increasing thermostability often reduces activity at gut temperatures and there remains a demand for improved phyases for a growing market.

Results

In this work, we present a thermostable variant of the E. coli AppA phytase, ApV1, that contains an extra non-consecutive disulfide bond. Detailed biochemical characterisation of ApV1 showed similar activity to the wild type, with no statistical differences in kcat and KM for phytic acid or in the pH and temperature activity optima. Yet, it retained approximately 50% activity after incubations for 20 min at 65, 75 and 85 °C compared to almost full inactivation of the wild-type enzyme. Production of ApV1 in Pichia pastoris (Komagataella phaffi) was much lower than the wild-type enzyme due to the presence of the extra non-consecutive disulfide bond. Production bottlenecks were explored using bidirectional promoters for co-expression of folding chaperones. Co-expression of protein disulfide bond isomerase (Pdi) increased production of ApV1 by ~ 12-fold compared to expression without this folding catalyst and restored yields to similar levels seen with the wild-type enzyme.

Conclusions

Overall, the results show that protein engineering for enhanced enzymatic properties like thermostability may result in folding complexity and decreased production in microbial systems. Hence parallel development of improved production strains is imperative to achieve the desirable levels of recombinant protein for industrial processes.
A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia
Authors: Park Eun-Ah , Kim Juri , Shin Mee Young , Park Soon-Jung
Published: March 2021

Background

Polo-like kinases (PLKs) are conserved serine/threonine kinases that regulate the cell cycle. To date, the role of Giardia lamblia PLK (GlPLK) in cells has not been studied. Here, we report our investigation on the function of GlPLK to provide insight into the role of this PKL in Giardia cell division, especially during cytokinesis and flagella formation.

Methods

To assess the function of GIPLK, Giardia trophozoites were treated with the PLK-specific inhibitor GW843286X (GW). Using a putative open reading frame for the PLK identified in the Giardia genomic database, we generated a transgenic Giardia expressing hemagglutinin (HA)-tagged GlPLK and used this transgenic for immunofluorescence assays (IFAs). GlPLK expression was knocked down using an anti-glplk morpholino to observe its effect on the number of nuclei number and length of flagella. Giardia cells ectopically expressing truncated GlPLKs, kinase domain + linker (GlPLK-KDL) or polo-box domains (GlPLK-PBD) were constructed for IFAs. Mutant GlPLKs at Lys51, Thr179 and Thr183 were generated by site-directed mutagenesis and then used for the kinase assay. To elucidate the role of phosphorylated GlPLK, the phosphorylation residues were mutated and expressed in Giardia trophozoites

Results

After incubating trophozoites with 5 μM GW, the percentage of cells with > 4 nuclei and longer caudal and anterior flagella increased. IFAs indicated that GlPLK was localized to basal bodies and flagella and was present at mitotic spindles in dividing cells. Morpholino-mediated GlPLK knockdown resulted in the same phenotypes as those observed in GW-treated cells. In contrast to Giardia expressing GlPLK-PBD, Giardia expressing GlPLK-KDL was defective in terms of GIPLK localization to mitotic spindles and had altered localization of the basal bodies in dividing cells. Kinase assays using mutant recombinant GlPLKs indicated that mutation at Lys51 or at both Thr179 and Thr183 resulted in loss of kinase activity. Giardia expressing these mutant GlPLKs also demonstrated defects in cell growth, cytokinesis and flagella formation.

Conclusions

These data indicate that GlPLK plays a role in Giardia cell division, especially during cytokinesis, and that it is also involved in flagella formation.

Graphical Abstract