bluuebunny/crossref_metadata_2025 huggingface dataset:
P199 The reliability of using ultrasound for the detection of hypoechogenicity of enthesitis in patients with spondyloarthropathies
Authors: Aldahes Asma S , Wakefield Richard , Smith Kate
Published: April 2021

Background/Aims 

Enthesitis, which is the inflammation of the entheses area where the tendon or ligaments are attached into the bone, is considered a hallmark and pathological feature for spondyloarthropathies (SpA). The lower limb entheses are more prone to being affected than the upper extremity enthesis, the most common one is Achilles tendon where heel enthesitis is considered the most frequent finding in SpA patients. Ultrasound is widely used by rheumatologists because it has higher sensitivity and specificity in detecting enthesitis compared with clinical assessment. The abnormal characteristics of enthesitis in greyscale ultrasound includes the hypoechoic area at the insertion or body of the tendon due to the loss of the normal fibrillar pattern, increase in the tendon thickness, bone erosion, calcification and increase in Dopplar signals. Although ultrasound has many advantages compared with other imaging modalities, it is operator-dependent and the diagnosis is exposed to the subjectivity of the observer, which leads to the variability in defining the abnormal features of enthesitis. Using static ultrasound images of Achilles tendon entheses of patients with SpA, we first determined the intra- and inter-observer reliability of grading ‘hypoechogenicity’ using a panel of readers and second, compared a computerised pixel counting method against an expert consensus score to determine the level of agreement between approaches.

Methods 

Six participants (rheumatologists and sonographer) with experience in ultrasound scored the presence of hypoechogenicity in 100 static images of Achilles tendon entheses of patients with SpA. Two scoring systems were used- an OMERACT derived SQ system (0-3) of the whole enthesis and binary score system of the distal 2mm (0-1). The intra-class correlation coefficient (ICC) and Cohen's kappa was used to assess inter-observer reliability. The ImageJ software was used to measure the mean grey values (MGV) of the pixels within the enthesis.

Results 

The inter-observer reliability was good for using the SQ score (ICC 0.780 (95% CI 0.691-0.849) and moderate for the binary score (ICC 0.632 (95% CI 0.490-0.745)). There was no match between the results from the quantitative score of the pixels MGV and the expert semi-quantitative score.

Conclusion 

This study is novel as in that it has specifically evaluated the scoring of hypoechogenicity within the entheses of patients with SpA. It has demonstrated variation in scoring between observers and highlighted the challenges of image interpretation. A lack of correlation of expert scoring with the manual pixel MGV was limited by the image artefacts and different machine settings which may have implications as we work towards future AI systems.

Disclosure 

A.S. Aldahes: None. R. Wakefield: None. K. Smith: None.
Epidemiology of snakebites in Kuwait
Authors: Al-Sayegh Mohammed T , Hani Rihan Bani , Warrell David A , Amr Zuhair S
Published: April 2021

Fifty-two confirmed cases of snakebites in Kuwait were recorded during 2015–2019. The male:female ratio was almost 2:1 and 84.6% of the victims were between 1 and 20 y of age and 14.4% were >30 y. Snakebites peaked in October (23.1%) and July (17.3%), with the lowest number of recorded cases in March.
Association Between Benzodiazepine and Opioid Prescription and Mortality Among Patients in a Large Healthcare System
Authors: Mooney Larissa J. , Zhu Yuhui , Yoo Caroline K. , Wolitzky-Taylor Kate , Hser Yih-Ing
Published: April 2021

Objective:

Coprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system.

Methods:

Using data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality.

Results:

About 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15–1.55 per 10 mg/d increment) and opioids (OR = 1.04, 95%CI: 1.02–1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) = 3.83, 95%CI: 1.78–8.21).

Conclusions:

Study findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.
Montage-related Variability in the Characteristics of Envelope Following Responses
Authors: Urichuk Matthew , Easwar Vijayalakshmi , Purcell David
Published: April 2021

Objectives:

The study aimed to compare two electrode montages commonly used for recording speech-evoked envelope following responses.

Design:

Twenty-three normal-hearing adults participated in this study. EFRs were elicited by a naturally spoken, modified /susa∫i/ stimulus presented at 65 dB SPL monaurally. EFRs were recorded using two single-channel electrode montages: Cz-nape and Fz-ipsilateral mastoid, where the noninverting and inverting sites were the vertex and nape, and the high forehead and ipsilateral mastoid, respectively. Montage order was counterbalanced across participants.

Results:

Envelope following responses amplitude and phase coherence were significantly higher overall in the Cz-nape montage with no significant differences in noise amplitude. Post hoc testing on montage effects in response amplitude and phase coherence was not significant for individual stimuli. The Cz-nape montage also resulted in a greater number of detections and analyzed using the Hotelling’s T2.

Conclusions:

Electrode montage influences the estimated characteristics of speech-evoked EFRs.
The heterogeneity of population with high risk for melanoma and other skin cancer: a latent class analysis
Authors: Stojanović Larisa , Bajić Žarko
Published: April 2021

Objective

To examine whether there is heterogeneity in the risk factors for skin cancer among the high-risk population in Slovenia, a Central European country with the second-largest age-standardized melanoma-related mortality rate in Europe.

Methods

We analyzed data collected during the ‘Euromelanoma Day’ 2010–2019. The outcome was the prevalence of newly suspected skin cancer. The independent variables were 17 known risk factors and protective behaviors. We performed a latent class analysis with skin cancer as a covariate.

Results

We analyzed data from 1711 participants with a median (interquartile range) age of 52 (39–63) years, 52% of whom were women. During the 10 years, 81 cases of melanoma and 213 cases of other skin cancers were suspected. The model with three latent classes had the best fit. Two latent classes had a high risk for melanoma and other skin cancer: 3 and 19% respectively in class 2; 14 and 29% in class 3. The largest significant differences between the two high-risk classes were the older age and lower frequency of sunscreen use in high-risk class 2 and the number of atypical nevi, a large number of common moles, many moles as the primary motive to participate in Euromelanoma examination and having a skin phototype I or II in the highest-risk latent class 3.

Conclusions

There is heterogeneity in the risk factors for skin cancer among the Euromelanoma high-risk population. This heterogeneity should be tested in other countries, and if the findings are consistent, they should be used to refine secondary prevention programs.
Patient Release and Instructions for Lutetium Dotatate Radiopharmaceutical Therapy
Authors: Underwood James , Sturchio Glenn , Arnold Susan
Published: April 2021

Lutetium Dotatate radiopharmaceutical therapy (Lutathera) was approved by the United States Food and Drug Administration in 2018 and is used to treat somatostatin receptor positive neuroendocrine tumors. With all new radiopharmaceutical therapies, the radiation exposure to members of the public from the patient who received the therapy must be within regulatory limits and safe. If the patient will expose members of the public to too much radiation, the therapy must be performed on an inpatient basis. This paper shows that the administration of Lutathera can be done on an outpatient basis and provides safety and travel restrictions that should be communicated to the patient prior to leaving. The guidance presented herein serves as a basis for medical institutions looking to use Lutathera to treat patients.
Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes
Authors: El-Nimri Nevin W. , Manalastas Patricia Isabel C. , Zangwill Linda M. , Proudfoot James A. , Bowd Christopher , Hou Huiyuan , Moghimi Sasan , Penteado Rafaella C. , Rezapour Jasmin , Ekici Eren , Shoji Takuhei , Ghahari Elham , Yarmohammadi Adeleh , Weinreb Robert N.
Published: April 2021

Precis:

Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma.

Purpose:

The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes.

Materials and Methods:

Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups.

Results:

Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001).

Conclusions:

SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.
Cultivating Resilience Among Perinatal Care Providers During the Covid-19 Pandemic
Authors: Wright Erin M. , Carson Anna Melissa , Kriebs Jan
Published: April 2021

The Covid-19 pandemic has further illuminated the already existing need for methods of building resilience in perinatal caregivers. Using a scoping review approach, literature was examined to identify evidence-based models of resilience building in a cohort of perinatal clinicians. Research published between January 2015 and 2020 was evaluated using PubMed, CINAHL, EMBASE, and PsycINFO databases. Of the initial 3399 records reviewed, 2 qualitative studies met the inclusion criteria. Given the deleterious effects of Covid-19 on perinatal care providers, and in light of the paucity of available studies, personnel, time, and funding should be allocated for research to address these issues.
Preparing for the Worst or Hoping for the Best? The State of Fall Training in Prosthesis Users
Authors: Noble Charles , Fiedler Goeran
Published: April 2021

Introduction

The risk of accidental falls is greater in people with lower-limb loss than in their able-bodied peers. Most popular strategies to mitigate injuries from such falls include technical solutions that prevent falls or protect vulnerable body segments from destructive forces. Fall training is another effective intervention, but little evidence on its use in prosthesis users has been published. This research had the goal to investigate to what extent fall training is provided to the target population and what factors may be obstacles to its wider adoption.

Methods

An online questionnaire was developed and administered nationwide, targeting people with lower-limb loss. Descriptive statistics were used to describe the availability of fall training, and a logistic regression was performed to investigate variables that predict whether an individual receives fall training or not.

Results

A total of 180 responses was recorded, 166 of which were included in the analysis. More than two-thirds of respondents had not received fall training. Those who had physical therapy as part of their rehabilitation regimen were 3.7 times more likely to also have had fall training.

Discussion

Our data suggest that the potential benefits of providing fall training to people with lower-limb loss are not being fully realized. Interdisciplinary collaboration between prosthetists and therapists can help expand access to fall training interventions to better prepare patients for the likely event of an accidental fall.
Lipid effects of glucagon-like peptide 1 receptor analogs
Authors: Berberich Amanda J. , Hegele Robert A.
Published: April 2021

Purpose of review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming more prominent as a therapeutic choice in diabetes management and their use is being expanded to other indications, such as obesity. Dyslipidemia and cardiovascular disease are common co-morbidities in these populations and understanding the impact of this class of medications on the lipid profile may be an important consideration.

Recent findings

Several GLP-1RAs trials demonstrate them to be safe and potentially beneficial for cardiovascular outcomes; improvements in surrogate markers of atherosclerosis have also been observed. Lipid data collected as secondary outcomes from large clinical trials as well as some smaller dedicated trials show that GLP-1RAs can modestly lower low-density lipoprotein (LDL) and total cholesterol (C), and most show modest fasting triglyceride (TG) lowering. Effects on high-density lipoprotein-C have been less consistent. Some have also demonstrated substantial blunting of the postprandial rise in serum TGs. Favorable effects on lipoprotein metabolism, with reduced levels of small dense LDL particles and decreased atherogenic potential of oxidized LDL, have also been seen. Mechanisms underlying these observations have been investigated.

This review summarizes the data available on the lipid effects of GLP-1RAs, and explores the current understanding of the mechanisms underlying these observed effects.
The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma
Authors: Morichika Kazuho , Karube Kennosuke , Sakihama Shugo , Watanabe Risa , Kawaki Mamoru , Nishi Yukiko , Nakachi Sawako , Okamoto Shiki , Takahara Taishi , Satou Akira , Shimada Satoko , Shimada Kazuyuki , Tsuzuki Toyonori , Fukushima Takuya , Morishima Satoko , Masuzaki Hiroaki
Published: April 2021

On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as ≥40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P<0.001). Factors potentially activating STAT3, MYD88
L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P=0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.
Consensus Recommendations for Blood Culture Use in Critically Ill Children Using a Modified Delphi Approach*
Authors: Woods-Hill Charlotte Z. , Koontz Danielle W. , Voskertchian Annie , Xie Anping , Shea Judy , Miller Marlene R. , Fackler James C. , Milstone Aaron M.
Published: April 2021

Objectives:

Blood cultures are fundamental in evaluating for sepsis, but excessive cultures can lead to false-positive results and unnecessary antibiotics. Our objective was to create consensus recommendations focusing on when to safely avoid blood cultures in PICU patients.

Design:

A panel of 29 multidisciplinary experts engaged in a two-part modified Delphi process. Round 1 consisted of a literature summary and an electronic survey sent to invited participants. In the survey, participants rated a series of recommendations about when to avoid blood cultures on five-point Likert scale. Consensus was achieved for the recommendation(s) if 75% of respondents chose a score of 4 or 5, and these were included in the final recommendations. Any recommendations that did not meet these a priori criteria for consensus were discussed during the in-person expert panel review (Round 2). Round 2 was facilitated by an independent expert in consensus methodology. After a review of the survey results, comments from round 1, and group discussion, the panelists voted on these recommendations in real-time.

Setting:

Experts’ institutions; in-person discussion in Baltimore, MD.

Subjects:

Experts in pediatric critical care, infectious diseases, nephrology, oncology, and laboratory medicine.

Interventions:

None.

Measurements and Main Results:

Of the 27 original recommendations, 18 met criteria for achieving consensus in Round 1; some were modified for clarity or condensed from multiple into single recommendations during Round 2. The remaining nine recommendations were discussed and modified until consensus was achieved during Round 2, which had 26 real-time voting participants. The final document contains 19 recommendations.

Conclusions:

Using a modified Delphi process, we created consensus recommendations on when to avoid blood cultures and prevent overuse in the PICU. These recommendations are a critical step in disseminating diagnostic stewardship on a wider scale in critically ill children.
Laser-free super-resolution microscopy
Authors: Prakash Kirti
Published: April 2021

We report that high-density single-molecule super-resolution microscopy can be achieved with a conventional epifluorescence microscope set-up and a mercury arc lamp. The configuration termed as laser-free super-resolution microscopy (LFSM) is an extension of single-molecule localization microscopy (SMLM) techniques and allows single molecules to be switched on and off (a phenomenon termed as ‘blinking’), detected and localized. The use of a short burst of deep blue excitation (350–380 nm) can be further used to reactivate the blinking, once the blinking process has slowed or stopped. A resolution of 90 nm is achieved on test specimens (mouse and amphibian meiotic chromosomes). Finally, we demonstrate that stimulated emission depletion and LFSM can be performed on the same biological sample using a simple commercial mounting medium. It is hoped that this type of correlative imaging will provide a basis for a further enhanced resolution.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)’.
Serratia rhizosphaerae sp. nov., a novel plant resistance inducer against soft rot disease in tobacco
Authors: Son Jin-Soo , Hwang Ye-Ji , Lee Soo-Yeong , Ghim Sa-Youl
Published: April 2021

A novel Gram-negative, facultatively anaerobic, non-spore-forming and rod-shaped bacterial strain (KUDC3025T) was isolated from rhizospheric soil of Artemisia japonica subsp. littoricola collected from the Dokdo Islands, Republic of Korea and bacterial strain MYb239 was isolated from compost from Kiel, Germany. Phylogenetic analysis based on 16S rRNA gene sequences, multilocus genes (atpD, gyrB, infB and rpoB), and whole-genome sequences indicated that both strains belonged to the genus

Serratia

and were most closely related to

Serratia rubidaea

KCTC 2927T. The average nucleotide identity values based on blast and MUMmer, tetranucleotide usage pattern and genome-based digital DNA–DNA hybridization values were all below the 95.0 %/95.0 %/0.998/70 % cutoff points. The genome G+C content was 58.0 mol%. The cellular quinone content contained ubiquinone-8 and the major components in the fatty acid profile were C16 : 0, C17 : 0 cyclo and C14 : 0. The polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unknown amino lipids, two unknown phospholipids and an unknown lipid. Based on phenotypic, chemotaxonomic and genotypic data, strain KUDC3025T (DSM 106578T=CGMCC 1.18473T) and MYb239 represents a novel species, for which the name Serratia rhizosphaerae sp. nov. is proposed. Furthermore, strain KUDC3025T was able to suppress disease symptoms by priming the plant defence system components, including the salicylic acid and ethylene pathways, furthering our understanding of

Serratia

as potential plant growth promoting bacteria.
Impact of national and regional lockdowns on COVID-19 epidemic waves: Application to the 2020 spring wave in France
Authors: Roux Jonathan , Massonnaud Clément , Colizza Vittoria , Cauchemez Simon , Crépey Pascal
Published: April 2021

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like “where” and “when” still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increases. However, the public health costs associated with these delays tend to grow exponentially with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality and stress on the healthcare system.
Imputation of PaO2 from SpO2 values from the MIMIC-III Critical Care Database Using Machine-Learning Based Algorithms
Authors: Ren Shuangxia , Zupetic Jill , Nouraie Mehdi , Lu Xinghua , Boyce Richard D. , Lee Janet S.
Published: April 2021

Background

The partial pressure of oxygen (PaO2)/fraction of oxygen delivered (FIO2) ratio is the reference standard for assessment of hypoxemia in mechanically ventilated patients. Non-invasive monitoring with the peripheral saturation of oxygen (SpO2) is increasingly utilized to estimate PaO2 because it does not require invasive sampling. Several equations have been reported to impute PaO2/FIO2 from SpO2 /FIO2. However, machine-learning algorithms to impute the PaO2 from the SpO2 has not been compared to published equations.

Research Question

How do machine learning algorithms perform at predicting the PaO2 from SpO2 compared to previously published equations?

Methods

Three machine learning algorithms (neural network, regression, and kernel-based methods) were developed using 7 clinical variable features (n=9,900 ICU events) and subsequently 3 features (n=20,198 ICU events) as input into the models from data available in mechanically ventilated patients from the Medical Information Mart for Intensive Care (MIMIC) III database. As a regression task, the machine learning models were used to impute PaO2 values. As a classification task, the models were used to predict patients with moderate-to-severe hypoxemic respiratory failure based on a clinically relevant cut-off of PaO2/FIO2 ≤ 150. The accuracy of the machine learning models was compared to published log-linear and non-linear equations. An online imputation calculator was created.

Results

Compared to seven features, three features (SpO2, FiO2 and PEEP) were sufficient to impute PaO2/FIO2 ratio using a large dataset. Any of the tested machine learning models enabled imputation of PaO2/FIO2 from the SpO2/FIO2 with lower error and had greater accuracy in predicting PaO2/FIO2 ≤ 150 compared to published equations. Using three features, the machine learning models showed superior performance in imputing PaO2 across the entire span of SpO2 values, including those ≥ 97%.

Interpretation

The improved performance shown for the machine learning algorithms suggests a promising framework for future use in large datasets.
Predicting the end of Covid-19 infection for various countries using a stochastic agent-based model taking into account vaccination rates and the new mutant
Authors: Eissler Manfred
Published: April 2021

Using a stochastic, agent-based model, the course of infection since the first occurrence of a Covid-19 infection is simulated for various countries, taking into account the new, more infectious mutant and the vaccinations. The simulation shows that the course of infection for the United Kingdom (UK) and Israel is surprisingly good. For the other countries, an end date for the infection can be predicted based on the course of the simulation. For Germany, the course is calculated in a second scenario, assuming a higher vaccination rate.
Indirect Effects of COVID-19 on Maternal, Neonatal, Child, Sexual and Reproductive Health Services in Kampala, Uganda
Authors: Burt Jessica Florence , Ouma Joseph , Lubyayi Lawrence , Amone Alexander , Aol Lorna , Sekikubo Musa , Nakimuli Annettee , Nakabembe Eve , Mboizi Robert , Musoke Philippa , Kyohere Mary , Namara Emily , Khalil Asma , Le Doare Kirsty
Published: April 2021

Background: COVID-19 has impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown which severely limited the movements of individuals in Uganda will have impacted access to services.
Methods: An observational study, using routinely collected health data from Electronic Medical Records was carried out, utilising data from July 2019 to December 2020 in Kawempe district, Kampala. The mean and 95% confidence intervals were calculated pre-COVID (July 2019-February 2020) and post-COVID (March-December 2020). The means were compared using t-tests, and the monthly totals analysed as to whether they lay within or outside the normal range, compared to the previous 9 months.
Results: Antenatal attendances decreased 96% in April 2020 and remain below pre-COVID levels. We found a rise in adverse pregnancy outcomes for Caesarean sections (5%), haemorrhages related to pregnancy (51%), stillbirths (31%) and low-birth-weight (162%) and premature infant births (400%). We noted a drop in neonatal unit admissions, immunisation clinic attendance and delivery of all vaccinations except measles. There was an immediate drop in clinic attendance for prevention of mother to child transmission of HIV (now stabilised) and an increase of 348% in childhood malnutrition clinic attendance. Maternal and neonatal deaths, immediate post-natal care and contraceptive provision remained within normal limits.
Conclusion: The response to COVID-19 in Uganda has negatively impacted maternal, child and neonatal health, with the biggest and longest lasting impact seen in complications of pregnancy, stillbirths and low-birthweight infants likely due to delayed care-seeking behaviour. The decline in vaccination clinic attendance has implications for all vaccine-preventable diseases, with a cohort of infants currently unprotected. Further consideration of the impacts of restricting movement and limiting access to preventative services must be undertaken in responding to future pandemics if key maternal and child health services are to be maintained.
Household transmission of SARS-CoV-2 from humans to pets in Washington and Idaho: burden and risk factors
Authors: Meisner Julianne , Baszler Timothy V. , Kuehl Kathryn H. , Ramirez Vickie , Baines Anna , Frisbie Lauren A. , Lofgren Eric T. , DeAvila David M. , Wolking Rebecca M. , Bradway Dan S. , Wilson Hannah , Lipton Beth , Kawakami Vance , Rabinowitz Peter M.
Published: April 2021

SARS-CoV-2 is believed to have emerged from an animal reservoir; however, the frequency of and risk factors for inter-species transmission remain unclear. We carried out a community-based study of pets in households with one or more confirmed SARS-CoV-2 infection in humans. Among 119 dogs and 57 cats with completed surveys, clinical signs consistent with SARS-CoV-2 were reported in 20 dogs (21%) and 19 cats (39%). Out of 81 dogs and 32 cats sampled for testing, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive; this discordance may be due to delays in sampling. Respondents commonly reported close human-animal contact and willingness to take measures to prevent transmission to their pets. Reported preventative measures showed a slightly protective trend for both illness and seropositivity in pets, while sharing of beds and bowls had slight harmful effects.
Kaposi’s Sarcoma-associated Herpesvirus Promotes Mesenchymal-to-Endothelial Transition by Resolving the Bivalent Chromatin of PROX1 Gene
Authors: Ding Yao , Chen Weikang , Lu Zhengzhou , Wang Yan , Yuan Yan
Published: April 2021

Human mesenchymal stem cells (MSCs) are highly susceptible to Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, and the infection promotes mesenchymal-to-endothelial transition (MEndT) and acquisition of Kaposi’s sarcoma (KS)-like phenotypes. Increasing evidence suggests that KS may arise from KSHV-infected MSCs. To understand how KSHV induces MEndT and transforms MSCs to KS cells, we investigated the mechanism underlying KSHV-mediated MSC endothelial lineage differentiation. Like embryonic stem cells, MSC differentiation and fate determination are under epigenetic control. Prospero homeobox 1 (PROX1) is a master regulator that controls lymphatic vessel development and endothelial differentiation. We found that the PROX1 gene in MSCs harbors a distinctive bivalent epigenetic signature consisting of both active marker H3K4me3 and repressive marker H3K27me3, which poises expression of the genes, allowing timely activation upon differentiation signals or environmental stimuli. KSHV infection effectively resolved the bivalent chromatin by decreased H3K27me3 and increased H3K4me3 to activate the PROX1 gene. vIL-6 signaling leads to the recruitment of MLL2 and Set1 complexes to the PROX1 promoter to increase H3K4me3, and the vGPCR-VEGF-A axis is responsible for removing PRC2 from the promoter to reduce H3K27me3. Therefore, through a dual signaling process, KSHV activates PROX1 gene expression and initiates MEndT, which renders MSC tumorigenic features including angiogenesis, invasion and migration.
Super-resolution microscopy informs on the molecular architecture of alpha-synuclein inclusions in model systems and in the human brain
Authors: Weish Patrick , Lázaro Diana F. , Palmares Luís , Santos Patrícia I. , Stadelmann Christine , Höglinger Günter U. , Rizzoli Silvio O. , Outeiro Tiago F.
Published: April 2021

Lewy bodies (LBs) and Lewy neurites are pathological hallmarks of Parkinson’s disease and other progressive neurodegenerative disorders known as Lewy body diseases (LBD). These proteinaceous deposits are immunopositive for alpha-synuclein (aSyn) and several other proteins, as neurofilament components. The structural organization and composition of aSyn inclusions is still unclear and needs to be addressed in greater detail, as this may open novel avenues for our understanding of the disease-relevant pathological events.

In this study, we investigated the molecular architecture of aSyn inclusions, both in cell models and in human brain tissue, using state-of-art super resolution X10 Expansion microscopy (ExM). This approach physically expands specimens embedded into a swellable gel, preserving their biological information. Then, the specimen can be analyzed using standard epifluorescence microscopes, thereby obtaining nanoscale information.

The combination of different cell models, mouse and human brain tissue enabled us to distinguish different types aSyn assemblies (e.g. ring shape or tubular structures), and a conserved pattern of aSyn inclusions surrounded/encaged by intermediate filament proteins. Overall, X10 ExM enabled us to gain insight into the architecture and biology of aSyn inclusions and constitutes a powerful tool in the quest to understanding underlying disease mechanisms in synucleinopathies.
Engineering a super-secreting strain ofEscherichia coliby directed co-evolution of the multiprotein Tat translocation machinery
Authors: Taw May N. , Li Mingji , Kim Daniel , Rocco Mark A. , Waraho-Zhmayev Dujduan , DeLisa Matthew P.
Published: April 2021

Escherichia coliremains one of the preferred hosts for biotechnological protein production due to its robust growth in culture and ease of genetic manipulation. It is often desirable to export recombinant proteins into the periplasmic space for reasons related to proper disulfide bond formation, prevention of aggregation and proteolytic degradation, and ease of purification. One such system for expressing heterologous secreted proteins is the twin-arginine translocation (Tat) pathway, which has the unique advantage of delivering correctly folded proteins into the periplasm. However, transit times for proteins through the Tat translocase, comprised of the TatABC proteins, are much longer than for passage through the SecYEG pore, the translocase associated with the more widely utilized Sec pathway. To date, a high protein flux through the Tat pathway has yet to be demonstrated. To address this shortcoming, we employed a directed co-evolution strategy to isolate mutant Tat translocases for their ability to deliver higher quantities of heterologous proteins into the periplasm. Three super-secreting translocases were selected that each exported a panel of recombinant proteins at levels that were significantly greater than that observed for wildtype TatABC or SecYEG translocases. Interestingly, all three of the evolved Tat translocases exhibited quality control suppression, suggesting that increased translocation flux was gained by relaxation of substrate proofreading. Overall, our discovery of highly efficient translocase variants paves the way for the use of the Tat system as a powerful complement to the Sec pathway for secreted production of both commodity and high value-added proteins.
Systematic analysis of Epstein-Barr virus genes and their individual contribution to virus production and composition
Authors: Chen Yen-Fu Adam , Mocanu Bianca , Akidil Ezgi , Pich Dagmar , Mautner Josef , Hammerschmidt Wolfgang
Published: April 2021

Epstein-Barr virus (EBV), a member of the large herpesvirus family is a very complex humanγ-herpesvirus. Its complexity with respect to viral gene regulation, its preferred latent life style and technical difficulties are major obstacles, which hinder efficient virus generationin vitroto mass-produce or establish recombinant wild-type EBV or mutant derivatives. To explore conditions optimizing and improving virus production, we established and tested an EBV gene library with 77 expression plasmids and a set of designed shRNAs. With this tool set we investigated the contributions of individual viral genes in the context of virus synthesis and virion functions. Engineered virus stocks were systematically analyzed with respect to physical and bioparticle concentration, virus titer and virus uptake by primary human B cells, EBV’s target cellsin vivo. To quantitate virus uptake by these cells, we developed a novelß-lactamase-based assay that can monitor fusion events of the viral envelope with membranes of recipient cells at the level of single cells. Based on our findings, EBV does not encode a dominant regulator that governs virus production, but our results identified several EBV genes such as BALF4, BVLF1 and BKRF4, encoding a viral glycoprotein, a transcriptional regulator of late viral genes, and a possible tegument protein, respectively, that improve virus production regarding virus yield, virus composition and quality, and virus uptake by primary human B cells.

Importance

For more than 20 years HEK293 cells have been instrumental to produce virus stocks of recombinant EBV. The identification of this cell line as a source of infectious EB virions was unexpected because HEK293 cells are very distant from B cells and in particular plasma cells which produce EBV progenyin vivo. To our knowledge, no systematic analysis has addressed the fundamental question whether virus yield with respect to virus concentration, virion composition and functionality can be improved to produce recombinant EBV stocks in HEK293 cells. We tackled this question and analyzed 77 individual EBV genes for their possible contribution to virus yield. To analyze and compare different virus stocks we used established and developed novel assays to characterize important parameters of EB virions and their functions.
Deconvolving multiplexed histone modifications in single cells
Authors: Yeung Jake , Florescu Maria , Zeller Peter , de Barbanson Buys Anton , van Oudenaarden Alexander
Published: April 2021

Recent advances have enabled mapping of histone modifications in single cells1–12, but current methods are constrained to profile only one histone modification per cell. Here we present an integrated experimental and computational framework, scChIX (single-cell chromatin immunocleavage and unmixing), to map multiple histone modifications in single cells. scChIX multiplexes two histone modification profiles together in single cells, then computationally deconvolves the signal using training data from respective histone modification profiles. We first validate this method using purified blood cells and show that although the two repressive marks, H3K27me3 and H3K9me3, are generally mutually exclusive, the transitions between the two regions can vary between cell types. Next we apply scChIX to a heterogenous cell population from mouse bone marrow to generate linked maps of active (H3K4me1) and repressive (H3K27me3) chromatin landscapes in single cells, where coordinates in the active modification map correspond to coordinates in the repressive map. Linked analysis reveals that immunoglobulin genes in theIgkvregion are in a repressed chromatin state in pro-B cells, but become activated in B cells. Overall, scChIX unlocks systematic interrogation of the interplay between histone modifications in single cells.
Transition-metal complexes of group 12 with 1,1′-bis(phosphanyl)ferrocene ligands
Authors: Chaudhary Karan , Trivedi Manoj , Masram Dhanraj T. , Rath Nigam P.
Published: April 2021

The syntheses of four new cadmium and zinc complexes with 1,1′-bis(phosphanyl)ferrocene ligands and their phosphine chalcogenide derivatives are reported. The complexes were characterized by elemental analyses and IR,1H NMR,31P NMR and electronic absorption spectroscopy. The crystal structures of dichlorido[1-diphenylphosphinoyl-1′-(di-tert-butylphosphanyl)ferrocene-κ2O,P]cadmium(II), [CdCl2{(C17H14OP)(C13H22P)Fe}] or CdCl2(κ2P,O-dppOdtbpf) (1), bis[μ-(tert-butyl)(1′-diphenylphosphinoylferrocen-1-yl)phosphinato-κ3O,O′:O′′]bis[chloridozinc(II)], [Zn2{(C9H13O2P)(C17H14OP)Fe}2Cl2] or [ZnOCl{κ2O,O′-Ph2POFcPO2(t-Bu)}]2(2), 1,1′-bis(di-tert-butylthiophosphinoyl)ferrocene, [Fe(C13H22PS)2] or dtbpfS2(3), and [1,1′-bis(dicyclohexylphosphanyl)ferrocene-κ2P,P′][chlorido/cyanido(0.25/1.75)]zinc(II), [Zn(CN)1.75Cl0.25{(C17H26P)2Fe}] or Zn(CN)2(κ2-dcpf) (4), were determined crystallographically. Compound1has tetrahedral geometry in which the CdIIcentre is coordinated by one dppOdtbpf ligand in a κ2-manner and by two Cl atoms, while compound2displays a centrosymmetric dimeric unit in which two oxide atoms bridge the two Zn atoms to generate an eight-membered ring. Compound3revealed a sandwich structure with both phosphane groups sulfurized. In compound4, the ZnIIatom adopts a tetrahedral geometry by coordinating to the 1,1′-bis(dicyclohexylphosphanyl)ferrocene ligand in a κ2-manner and to two cyanide ligands.
Understanding the reliability of citizen science observational data using item response models
Authors: Santos‐Fernandez Edgar , Mengersen Kerrie
Published: April 2021

Citizen science projects have become increasingly popular in many fields, including ecology. However, the quality of this information is frequently debated within the scientific community. Modern citizen science implementations therefore require measures of the users' proficiency.

We introduce a new methodological framework of item response that quantifies a citizen scientist's ability, taking into account the difficulty of the task. We focus on citizen science programs involving the classification of images. Our approach accommodates spatial autocorrelation within the item difficulties, and provides deeper insights and relevant ecological measures of species and site‐related difficulties, discriminatory power and guessing behaviour. The identification of very capable versus less skilled participants can facilitate selective use of data in analyses and more targeted training programs for citizen scientists. This paper also addresses challenges in fitting such models to very large datasets.

We found that the suggested methods outperform the traditional item response models in terms of RMSE, accuracy and WAIC, based on leave‐one‐out cross‐validation on simulated and empirical data.

We present a comprehensive implementation using a case study of species identification in the Serengeti, Tanzania. The R and Stan codes are provided for full reproducibility. Multiple statistical illustrations and visualizations are given, which allow extrapolation to a wide range of citizen science ecological problems.
Craniofacial microsomia: Reflections on diagnosis and severity assessment based on a series of cases
Authors: Bergamini Luna Lira , Spineli‐Silva Samira , Félix Têmis Maria , Gil‐da‐Silva‐Lopes Vera L. , Vieira Tarsis P. , Ribeiro Erlane Marques , Xavier Ana Carolina , Lustosa‐Mendes Elaine , Fontes Marshall Ítalo Barros , Monlleó Isabella L.
Published: April 2021

This study aims to discuss diagnostic criteria and severity assessment for craniofacial microsomia (CFM). A series of 61 patients with diverse CFM phenotypes had their clinical data collected by experienced dysmorphologists using a single protocol. Genetic abnormalities were searched through karyotype and chromosomal microarray analysis. Sex ratio, prenatal risk factors, and recurrence rate corroborated the literature. Despite the wide variability of clinical findings, ear disruption was universal. Eight patients were assigned as syndromic, four of whom had demonstrable genetic alterations. The majority of patients (67.2%) fulfilled four known diagnostic criteria, while 9.8% fulfilled one of them. Data strengthened disruptions of the ear and deafness as a semiotically valuable sign in CFM. Facial impairment should consider asymmetry as a mild expression of microsomia. Spinal and cardiac anomalies, microcephaly, and developmental delay were prevalent among extra craniofacial features and should be screened before planning treatment and follow up. The severity index was able to recognize the less and the most affected patients. However, it was not useful to support therapeutic decisions and prognosis in the clinical scenario due to syndromic and non‐syndromic phenotypes overlapping. These issues make contemporary the debate on diagnostic methods and disease severity assessment for CFM. They also impact care and etiopathogenetic studies.
Long‐term surgical outcomes after resection of presacral tumours and risk factors associated with recurrence
Authors: Zhang Di , Sun Yizhou , Lian Lei , Hu Bang , Zhang Heng , Zou Qi , Huang Dandan , Ren Donglin
Published: April 2021

Aim

The incidence of presacral tumours is low and pertinent data on the management and outcomes after surgery are sparse. The aim of this study was to identify the risk factors for recurrence in patients with presacral tumours undergoing surgery at our institution.

Method

Patients undergoing resection of a presacral tumour between 2009 and 2019 were identified from a prospectively maintained database. Demographics, clinicopathological features, preoperative imaging, operative details, morbidity, mortality, recurrence and survival were investigated.

Results

A total of 122 patients were identified. There were 95 women (77.9%) and the median age was 34 years. The most common presenting symptoms included pelvic pain (n = 60, 49.2%) and recurrent abscesses or fistulas (n = 40, 32.8%). The accuracy of preoperative magnetic resonance imaging (MRI) in distinguishing malignant from benign tumours was 93.9%. Six patients underwent three‐dimensional computed tomography angiography (3D‐CTA) and preoperative interventional embolization. Procedures were performed using transabdominal (n = 9), posterior (n = 99) and combined abdominal and posterior (n = 14) approaches. There were 21 (17.2%) malignant and 101 (82.8%) benign tumours. The local recurrence rate was 33.3% for malignant tumours and 9.9% for benign tumours. Multivariate analysis revealed that recurrence of malignant tumours was associated with R1 resection while recurrence of benign tumours was associated with secondary resections and intraoperative lesion rupture.

Conclusion

Presacral tumours continue to be a diagnostic and therapeutic challenge. A multidisciplinary team, informed by modern imaging modalities, is essential for the management of presacral tumours.