bluuebunny/crossref_metadata_2025 huggingface dataset:
DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base
Authors: Rooper Lisa M. , Agaimy Abbas , Dickson Brendan C. , Dueber Julie C. , Eberhart Charles G. , Gagan Jeffrey , Hartmann Arndt , Khararjian Armen , London Nyall R. , MacMillan Christina M. , Palsgrove Doreen N. , Nix J. Stephen , Sandison Ann , Stoehr Robert , Truong Tra , Weinreb Ilan , Bishop Justin A.
Published: May 2021

A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. This study aims to characterize a larger cohort of carcinomas with DEK-AFF2 fusions to assess whether they truly constitute a distinctive entity. Among 27 sinonasal and skull base nonkeratinizing squamous cell carcinoma that were negative for human papillomavirus and Epstein-Barr virus, RNA sequencing identified DEK-AFF2 fusions in 13 cases (48%). Nine were centered in the nasal cavity, 2 in the middle ear/temporal bone, 1 in the nasopharynx, and 1 in the orbit. These tumors displayed recurrent histologic features including (1) complex endophytic and exophytic, frequently papilloma-like growth, (2) transitional epithelium with eosinophilic to amphophilic cytoplasm, (3) absent or minimal keratinization with occasional compact keratin pearls, (4) monotonous nuclei, and (5) prominent tumor-infiltrating neutrophils or stromal lymphocytes. This appearance not only overlaps with high-grade basaloid sinonasal carcinomas but also with benign papillomas and tumors reported as low-grade papillary Schneiderian carcinoma. However, DEK-AFF2 carcinomas showed frequent local recurrence, cervical lymph node metastases, and distant metastasis with 2 deaths from disease, confirming they are aggressive malignancies despite relatively bland histology. Overall, the distinctive molecular, histologic, and clinical features of DEK-AFF2 carcinomas suggest they represent a unique entity in the sinonasal region. This tumor merits increased pathologic recognition to better understand its prognostic and therapeutic implications.
Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion
Authors: Shibayama Takahiro , Shimoi Tatsunori , Mori Taisuke , Noguchi Emi , Honma Yoshitaka , Hijioka Susumu , Yoshida Masayuki , Ogawa Chitose , Yonemori Kan , Yatabe Yasushi , Yoshida Akihiko
Published: May 2021

ATF1, CREB1, and CREM, which encode the CREB family of transcription factors, are fused with EWSR1 or FUS in human neoplasms, such as angiomatoid fibrous histiocytoma. EWSR1/FUS-CREB fusions have recently been reported in a group of malignant epithelioid tumors with a predilection to the peritoneal cavity and frequent cytokeratin expression. Here, we studied 8 cytokeratin-positive abdominal malignancies with these fusions for further characterization. The tumors affected males (15 to 76 y old) and presented as intra-abdominal masses with concurrent or subsequent peritoneal dissemination, ascites, and/or metastases to the liver or lymph nodes. Four patients died of the disease within 18 to 140 months. Cases 1 to 5 showed multinodular growth of monomorphic epithelioid cells with focal serous cysts. Lymphoplasmacytic infiltration was prominent and was associated with systemic inflammatory symptoms. Two patients suffered from membranous nephropathy with nephrosis. The tumors displayed partly overlapping phenotypes with malignant mesothelioma, including diffuse strong expression of AE1/AE3 and WT1 and membranous positivity of sialylated HEG1, although calretinin was negative. Case 6 showed similar histology to cases 1 to 5, but expressed smooth muscle actin diffusely, lacked WT1 and HEG1, and harbored prominent pseudoangiomatous spaces. Cases 7 and 8 displayed dense growth of small oval to short spindle cells, with occasional molding and minor swirling, superficially resembling small cell carcinoma. Lymphoplasmacytic infiltration was not observed. The tumors were positive for AE1/AE3 and CD34 (focal), whereas calretinin, WT1, and HEG1 were negative. The detected fusions were FUS-CREM (n=4), EWSR1-ATF1 (n=2), EWSR1-CREB1 (n=1), and EWSR1-CREM (n=1). We confirmed the prior observation that these tumors do not fit perfectly with known entities and provided additional novel clinicopathologic information. The tumors require wider recognition because of more aggressive behavior than angiomatoid fibrous histiocytoma despite similar genetics, and potential misdiagnosis as unrelated diseases, such as neuroendocrine neoplasms.
Initial Results of Laparoscopic Proximal Gastrectomy With Double-tract Reconstruction Using Oblique Jejunogastrostomy Method on the Long-term Outcome of Postoperative Nutritional Status: A Propensity Score-matched Study
Authors: Kimura Kotaro , Ebihara Yuma , Tanaka Kimitaka , Nakanishi Yoshitsugu , Asano Toshimichi , Noji Takehiro , Kurashima Yo , Murakami Soichi , Nakamura Toru , Tsuchikawa Takahiro , Okamura Keisuke , Shichinohe Toshiaki , Hirano Satoshi
Published: May 2021

Background:

The aim of this study was to evaluate the long-term nutritional state of patients with gastric cancer who underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) using oblique jejunogastrostomy method (OJG).

Methods:

Medical records of 38 patients who underwent LPG-DTR using OJG (21 patients) or laparoscopic total gastrectomy with Roux-en-Y reconstruction (LTG-RY) (17 patients) between October 2011 and March 2018 were retrospectively reviewed. In these patients, clinicopathologic variables were analyzed using propensity score matching for age, sex, body mass index, American Society of Anesthesiologists physical state, clinical stage, and lymph node dissection. Operative outcomes and postoperative nutritional status were compared between the 2 groups.

Results:

A total of 16 patients were matched to analyze the LPG-DTR and LTG-RY groups. The serum hemoglobin, total protein, and albumin levels at 12 months postoperatively (P=0.008, 0.034, and 0.049) and serum hemoglobin level at 24 months (P=0.025) in the LPG-DTR group was significantly superior to those in the LTG-RY group.

Conclusions:

The postoperative nutritional status as long-term outcomes of patients who underwent LPG-DTR using OJG was significantly superior to those who underwent LTG-RY. The results hereby presented suggest that LPG-DTR using OJG for gastric cancer produces better postoperative nutritional status.
Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study
Authors: Chruscinski Andrzej , Juvet Stephen , Moshkelgosha Sajad , Renner Eberhard , Lilly Leslie , Selzner Nazia , Bredeson Christopher , Grant David , Adeyi Oyedele , Fischer Sandra , Demetris Anthony J. , Zhang Jianhua , Epstein Maor , Macarthur Meaghan , Clement Anne Marie , Khalili Korosh , Allan David , Altouri Sultan , Bence-Bruckler Isabelle , Cattral Mark , Fulcher Jill , Galvin Zita , Ghanekar Anand , Greig Paul , Huebsch Lothar , Humar Atul , Kew Andrea , Kekre Natasha , Kim Tae Kyoung , McDiarmid Sheryl , Martin Lisa , McGilvray Ian , Sabloff Mitchell , Sapisochin Gonzalo , Selzner Markus , Smith Robert , Tinckam Kathryn , Yi Tae Joon , Levy Gary , Atkins Harold
Published: May 2021

Background.

Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance.

Methods.

Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection, and cryopreserved. Immunoablation using busulfan, cyclophosphamide, and rabbit antithymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic, and clinical evidence of rejection while off immunosuppression at 2 y post-aHSCT.

Results.

Two of the 5 patients achieved operational tolerance with no clinical or histologic evidence of PSC progression or allorejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now >3 y after aHSCT. A fourth patient was weaned off immunosuppression but died 212 d after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T-cell clones, loss of autoantibodies, and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors.

Conclusions.

Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed render this specific protocol unsuitable for clinical adoption.
A step forward, but still inadequate: Australian health professionals’ views on the genetics and life insurance moratorium
Authors: Tiller Jane , Keogh Louise , McInerney-Leo Aideen , Belcher Andrea , Barlow-Stewart Kristine , Boughtwood Tiffany , Gleeson Penny , Dowling Grace , Prince Anya E.R. , Bombard Yvonne , Joly Yann , Delatycki Martin B , Winship Ingrid , Otlowski Margaret , Lacaze Paul
Published: May 2021

Background

In 2019, the Australian life insurance industry introduced a partial moratorium (ban) limiting the use of genetic test results in life insurance underwriting. The moratorium is industry self-regulated and applies only to policies below certain financial limits (eg AUD$500,000 of life cover).

Methods

We surveyed Australian health professionals (HPs) who discuss genetic testing with patients, to assess knowledge of the moratorium; reported patient experiences since its commencement; and HP views regarding regulation of genetic discrimination (GD) in Australia.

Results

Between April-June 2020, 166 eligible HPs responded to the online survey. Of these, 86% were aware of the moratorium, but <50% had attended related training/information sessions. Only 16% answered all knowledge questions correctly, yet 69% believed they had sufficient knowledge to advise patients. Genetics HPs’ awareness and knowledge were better than non-genetics HPs’ (p<0.05). There was some reported decrease in patients delaying/declining testing after the moratorium’s introduction, however 42% of HPs disagreed that patients were more willing to have testing post-moratorium. Although many (76%) felt the moratorium resolved some GD concerns, most (88%) still have concerns, primarily around self-regulation, financial limits and the moratorium’s temporary nature. Almost half (49%) of HPs reported being dissatisfied with the moratorium as a solution to GD. The majority (95%) felt government oversight is required, and 93% felt specific Australian legislation regarding GD is required.

Conclusion

While the current Australian moratorium is considered a step forward, most HPs believe it falls short of an adequate long-term regulatory solution to GD in life insurance.
Intrinsic capacity predicts negative health outcomes in older adults
Authors: Stolz Erwin , Mayerl Hannes , Freidl Wolfgang , Roller-Wirnsberger Regina , Gill Thomas M.
Published: May 2021

BACKGROUND

Monitoring trajectories of intrinsic capacity (IC) in older adults has been suggested by the WHO as a means to inform prevention to avoid or delay negative health outcomes. Due to a lack of longitudinal studies, it is currently unclear how IC changes over time and whether repeatedly measured IC predicts negative health outcomes.

METHODS

Based on 4,751 repeated observations of IC (range=0-100) during 21 years of follow-up among 754 older adults 70+ years, we assessed longitudinal trajectories of IC, and whether time-varying IC predicted the risk of chronic ADL disability, long-term nursing home stay, and mortality using joint models for longitudinal and time-to-event data.

RESULTS

Average IC declined progressively from 77 to 11 points during follow-up, with substantial heterogeneity between older adults. Adjusted for socio-demographics and chronic diseases, a one-point lower IC value was associated with a 7% increase in the risk of ADL disability, a 6% increase in the risk of a nursing home stay, and a 5% increase in mortality. Accuracy for 5- and 10-year predictions based on up to three repeated measurements of IC ranged between moderate and good (AUC = 0.76-0.82).

DISCUSSION

Our study indicates that IC declines progressively and that it predicts negative health outcomes among older adults. Therefore, regular monitoring of IC could work as an early warning system informing preventive efforts.
Variant-specific SARS-CoV-2 within-host kinetics
Authors: Elie Baptiste , Roquebert Bénédicte , Sofonea Mircea T. , Trombert-Paolantoni Sabine , Foulongne Vincent , Guedj Jérémie , Haim-Boukobza Stpéhanie , Alizon Samuel
Published: May 2021

Since early 2021, SARS-CoV-2 variants of concern (VOCs) have been causing epidemic rebounds in many countries. Their properties are well characterised at the epidemiological level but the potential underlying within-host determinants remain poorly understood. We analyse a longitudinal cohort of 6,944 individuals with 14,304 cycle threshold (Ct) values of qPCR VOC screening tests performed in the general population and hospitals in France between February 6 and August 21, 2021. To convert Ct values into numbers of virus copies, we performed an additional analysis using droplet digital PCR (ddPCR). We find that the number of viral genome copies reaches a higher peak value and has a slower decay rate in infections caused by Alpha variant compared to that caused by historical lineages. Following the evidence that viral genome copies in upper respiratory tract swabs are informative on contagiousness, we show that the kinetics of the Alpha variant translate into significantly higher transmission potentials, especially in older populations. Finally, comparing infections caused by the Alpha and Delta variants, we find no significant difference in the peak viral copy number. These results highlight that some of the differences between variants may be detected in virus load variations.
Strategies to Mitigate COVID-19 Resurgence Assuming Immunity Waning: A Study for Karnataka, India
Authors: Adiga Aniruddha , Athreya Siva , Lewis Bryan , Marathe Madhav V. , Rathod Nihesh , Sundaresan Rajesh , Swarup Samarth , Venkatramanan Srinivasan , Yasodharan Sarath
Published: May 2021

COVID-19 vaccination is being rolled out among the general population in India. Spatial heterogeneities exist in seroprevalence and active infections across India. Using a spatially explicit age-stratified model of Karnataka at the district level, we study three spatial vaccination allocation strategies under different vaccination capacities and a variety of non-pharmaceutical intervention (NPI) scenarios. The models are initialised using on-the-ground datasets that capture reported cases, seroprevalence estimates, seroreversion and vaccine rollout plans. The three vaccination strategies we consider are allocation in proportion to the district populations, allocation in inverse proportion to the seroprevalence estimates, and allocation in proportion to the case-incidence rates during a reference period.

The results suggest that the effectiveness of these strategies (in terms of cumulative cases at the end of a four-month horizon) are within 2% of each other, with allocation in proportion to population doing marginally better at the state level. The results suggest that the allocation schemes are robust and thus the focus should be on the easy to implement scheme based on population. Our immunity waning model predicts the possibility of a subsequent resurgence even under relatively strong NPIs. Finally, given a per-day vaccination capacity, our results suggest the level of NPIs needed for the healthcare infrastructure to handle a surge.
Dance Interventions for Individuals Post-Stroke - A Scoping Review Protocol
Authors: Kipnis Danielle , Kruusamäe Helena , King Miriam , Schreier Abigail , Quinn Lori , Shih Hai-Jung Steffi
Published: May 2021

The purpose of this scoping review will be to explore the current literature on dance interventions for individuals post-stroke. Specifically, we will conduct a systematic search of published studies to map the state of the literature on feasibility, intervention procedures, and efficacy of dance to improve health-related outcomes for individuals post-stroke. Stroke is the leading cause of long-term disability frequently causing motor and cognitive impairments that impact functional abilities. Dance inherently encompasses key principles of motor learning including cognitive-motor specific task practice, sensory feedback, and social engagement. Dance and music create an enriched environment, engaging emotion and promoting positive affect.

Electronic databases were searched in February 2021. Original, peer-reviewed studies will be included if they broadly describe the use of a dance intervention for individuals post-stroke. Studies including other neurological populations will be considered only if stroke results can be isolated. We will categorize studies based on dance style, study type, population characteristics, and study setting. We will narratively synthesize results, assessing feasibility, intervention procedures, and efficacy of dance to improve health-related outcomes in stroke survivors, including potential motor, cognitive, psychological, and social benefits.

This scoping review will be the first to broadly describe the existing literature on dance interventions for individuals post-stroke. We hope to identify trends in outcomes measures as well as reveal successes, limitations, and gaps in the literature to inform potential directions for future research in the field.
Impairment in acquisition of conditioned fear in schizophrenia: a pooled analysis of four studies
Authors: Tuominen Lauri , Romaniuk Liana , Milad Mohammed R. , Goff Donald C. , Hall Jeremy , Holt Daphne J.
Published: May 2021

Background

Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power.

Methods

To address this issue, data were pooled from 4 independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) during fear conditioning to stimuli that were paired (the CS+) and not paired (CS-) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS+ vs. CS-SCRs) and responses to CS+ and CS-separately were assessed.

Results

Acquisition of differential conditioned fear responses was significantly lower in individuals with schizophrenia than in healthy controls (Cohen’s d = 0.53). This effect was primarily related to a significantly higher response to the CS-stimulus in the schizophrenia compared to the control group. The magnitude of this response to the CS- in the schizophrenia group was correlated with the severity of delusional ideation. Other symptoms or antipsychotic dose were not associated with fear conditioning measures.

Conclusions

Individuals with schizophrenia who endorse delusional beliefs are over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of aberrant learning in psychosis.
Assessing multiplex tiling PCR sequencing approaches for detecting genomic variants of SARS-CoV-2 in municipal wastewater
Authors: Lin Xuan , Glier Melissa , Kuchinski Kevin , Mierlo Tenysha Ross-Van , McVea David , Tyson John R. , Prystajecky Natalie , Ziels Ryan M.
Published: May 2021

Wastewater-based genomic surveillance of the SARS-CoV-2 virus shows promise to complement genomic epidemiology efforts. Multiplex tiled PCR is a desirable approach for targeted genome sequencing of SARS-CoV-2 in wastewater due to its low cost and rapid turnaround time. However, it is not clear how different multiplex tiled PCR primer schemes or wastewater sample matrices impact the resulting SARS-CoV-2 genome coverage. The objective of this work was to assess the performance of three different multiplex primer schemes, consisting of 150bp, 400bp, and 1200bp amplicons, as well as two wastewater sample matrices, influent wastewater and primary sludge, for targeted genome sequencing of SARS-CoV-2. Wastewater samples were collected weekly from five municipal wastewater treatment plants (WWTPs) in the Metro Vancouver region of British Columbia, Canada during a period of increased COVID-19 case counts from February to April, 2021. RNA extracted from clarified influent wastewater provided significantly higher genome coverage (breadth and median depth) than primary sludge samples across all primer schemes. Shorter amplicons appeared more resilient to sample RNA degradation, but were hindered by greater primer pool complexity in the 150bp scheme. The identified optimal primer scheme (400bp) and sample matrix (influent) was capable of detecting the emergence of mutations associated with genomic variants of concern, of which the daily wastewater load significantly correlated with clinical case counts. Taken together, these results provide guidance on best practices for implementing wastewater-based genomic surveillance, and demonstrate its ability to inform epidemiology efforts by detecting genomic variants of concern circulating within a geographic region.

Importance

Monitoring the genomic characteristics of the SARS-CoV-2 virus circulating in a population can shed important insights into epidemiological aspects of the COVID-19 outbreak. Sequencing every clinical patient sample in a highly populous area is a difficult feat, and thus sequencing SARS-CoV-2 RNA in municipal wastewater offers great promise to augment genomic surveillance by characterizing a pooled population sample matrix, particularly during an escalating outbreak. Here, we assess different approaches and sample matrices for rapid targeted genome sequencing of SARS-CoV-2 in municipal wastewater. We demonstrate that the optimal approach is capable of detecting the emergence of SARS-CoV-2 genomic variants of concern, with strong correlations to clinical case data in the province of British Columbia. These results provide guidance on best practices on, as well as further support for, the application of wastewater genomic surveillance as a tool to augment current genomic epidemiology efforts.
Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment
Authors: Sekar Thillai V. , Elghonaimy Eslam A. , Swancutt Katy L. , Diegeler Sebastian , Gonzalez Isaac , Hamilton Cassandra , Leung Peter Q. , Meiler Jens , Martina Cristina E. , Whitney Michael , Aguilera Todd A.
Published: May 2021

In the rapidly advancing field of synthetic biology, there is a critical need for technology to discover targeting moieties for therapeutic biologics. We developed INSPIRE-seq, an approach that utilizes a nanobody library and next-generation sequencing to identify nanobodies selected for complex environments. INSPIRE-seq enables the parallel enrichment of immune cell-binding nanobodies that penetrate the tumor microenvironment. Clone enrichment and specificity varies across immune cell subtypes in the tumor, lymph node, and spleen. INSPIRE-seq identified a dendritic cell binding clone that binds PHB2. Single-cell RNA sequencing revealed a connection with cDC1s, and immunofluorescence confirmed nanobody-PHB2 colocalization along cell membranes. Structural modeling and docking studies assisted binding predictions and will guide nanobody selection. In this work, we demonstrate that INSPIRE-seq offers an unbiased approach to examine complex microenvironments and assist in the development of nanobodies, which could serve as active drugs, modified to become drugs, or used as targeting moieties.
The Evolutionary History of Small RNAs in the Solanaceae
Authors: Baldrich Patricia , Bélanger Sébastien , Kong Shuyao , Pokhrel Suresh , Tamim Saleh , Teng Chong , Schiebout Courtney , Gurazada Sai Guna Ranjan , Gupta Pallavi , Patel Parth , Razifard Hamid , Nakano Mayumi , Dusia Ayush , Meyers Blake C. , Frank Margaret H.
Published: May 2021

The Solanaceae or “nightshade” family is an economically important group that harbors a remarkable amount of diversity. To gain a better understanding of how the unique biology of the Solanaceae relates to the family’s small RNA genomic landscape, we downloaded over 255 publicly available small RNA datasets that comprise over 2.6 billion reads of sequence data. We applied a suite of computational tools to predict and annotate two major small RNA classes: (1) microRNAs (miRNAs), typically 20-22 nt RNAs generated from a hairpin precursor and functioning in gene silencing, and (2) short interfering RNAs (siRNAs), including 24-nt heterochromatic siRNAs (hc-siRNAs) typically functioning to repress repetitive regions of the genome via RNA-directed DNA methylation, as well as secondary phased siRNAs (phasiRNAs) and trans-acting siRNAs (tasiRNAs) generated via miRNA-directed cleavage of a Pol II-derived RNA precursor. Our analyses described thousands of small RNA loci, including poorly-understood clusters of 22-nt siRNAs that accumulate during viral infection. The birth, death, expansion, and contraction of these small RNA loci are dynamic evolutionary processes that characterize the Solanaceae family. These analyses indicate that individuals within the same genus share similar small RNA landscapes, whereas comparisons between distinct genera within the Solanaceae reveal relatively few commonalities.

ONE-SENTENCE SUMMARY

We use over 255 publicly-available small RNA datasets to characterize the small RNA landscape for the Solanaceae family.
Reflex single-gene non-invasive prenatal testing significantly increases the cost-effectiveness of carrier screening
Authors: Riku Shan , Hedriana Herman , Carozza Jacqueline A. , Hoskovec Jennifer
Published: May 2021

Objective

To evaluate the clinical and cost savings benefits of adoption of a carrier screen with reflex single-gene non-invasive prenatal test (sgNIPT) in prenatal care.

Method

A decision-analytic model was developed to compare carrier screen with reflex sgNIPT (maternal carrier status and fetal risk reported together) as first-line carrier screening to the traditional carrier screening workflow (positive maternal carrier screen followed by paternal screening to evaluate fetal risk). The model compared the clinical outcomes and cost effectiveness between the two screening methods. These results were used to simulate appropriate pricing for reflex sgNIPT.

Results

Reflex sgNIPT carrier screening detected 108 of 110 affected pregnancies per 100,000 births (98.5% sensitivity), whereas traditional carrier screening detected 46 of 110 affected pregnancies (41.5% sensitivity). The cost to identify one affected pregnancy was reduced by 62% in the reflex sgNIPT scenario compared to the traditional scenario. Adding together the testing cost savings and the savings from earlier clinical intervention made possible by reflex sgNIPT, the total cost savings was $37.6 million per 100,000 pregnancies. Based on these cost savings, we simulated appropriate reflex sgNIPT pricing range: if the cost to identify one affected pregnancy is the unit cost, carrier screening with reflex sgNIPT can be priced up to $1,859 per test (or $7,233 if sgNIPT is billed separately); if the cost per 100,000 pregnancies is the unit cost, carrier screening with sgNIPT can be priced up to $1,070 per test (or $2,336 if sgNIPT is billed separately).

Conclusion

Using the carrier screen with reflex sgNIPT as first-line screening improves the detection of affected fetuses by 2.4-fold and can save costs for the healthcare system. A real-life experience will be needed to assess the clinical utility and exact cost savings of carrier screen with reflex sgNIPT.
A systematic review and meta-analysis of non-workplace interventions to reduce time spent sedentary in adults
Authors: Hall Jessica Faye , Corepal Rekesh , Crocker Thomas F , Lam Natalie , Burton Louisa-Jane , Birch Karen , Carter Gill , Clarke David J , English Coralie , Farrin Amanda J , Fitzsimons Claire , Hall Jennifer , Holloway Ivana , Ozer Seline , Lawton Rebecca , Mead Gillian , Morton Sarah , Patel Anita , Forster Anne
Published: May 2021

Background

Sedentary behaviour has been the focus of considerable clinical, policy and research interest due to its detrimental effects on health and wellbeing. This systematic review aims to (1) develop a more precise description of different categories of interventions that aim to reduce sedentary time in adults by identifying specific components that form an intervention; (2) explore the effect of different categories of interventions in reducing time spent sedentary in adults.

Methods

Ten electronic databases, websites of relevant organisations (e.g. the Sedentary Behaviour Research Network), and relevant reviews were searched. Inclusion criteria: Randomised controlled trials (RCTs), including cluster and randomised cross-over trials, in the adult population (clinical and non-clinical). Any study including a measure of sedentary behaviour was included even if reducing sedentary behaviour was not the primary aim. Exclusion criteria: Interventions delivered in schools, colleges, or workplaces; studies investigating the immediate effects of breaking up sitting time as part of a supervised (usually laboratory-based) intervention. Two review authors conducted data extraction and quality assessment (GRADE approach).

Results

Searches identified 39,223 records, of which 85 studies met the inclusion criteria and were included in the review. Interventions shown to significantly reduce time spent sedentary were those which incorporated the provision of information, education, or support (advice/recommendations), in conjunction with either counselling (mean difference: -52.24 minutes/day; 95% CI: -85.37 to -19.10) or a form of structured/prescribed physical activity (standardised mean difference: -0.15; 95% CI: -0.23 to -0.07). However, this positive effect was not maintained at follow-up. No interventions were shown to break up prolonged sitting.

Conclusions

This review presents a novel way of categorising interventions according to the types of components they comprised. There is evidence that interventions might be effective in reducing time spent sedentary immediately post-intervention. There were limited studies measuring sustained behaviour change.
Assessment of mesalamine in the alterations of metabolic parameters in comorbid ulcerative colitis and metabolic syndrome patients: A retrospective study
Authors: Paniz Graziella R. , Arroyo-Mercado Fray M. , Ling Christina L. , Choi E. Eunice , Snow Harry E. , Rakov Neal E. , Castillo Eliseo F.
Published: May 2021

BACKGROUND & AIMS

It is unclear how the gut targeting medication mesalamine alters metabolic parameters associated with Metabolic Syndrome (MetS). We completed a retrospective analysis on ulcerative colitis (UC) and MetS comorbid patients receiving mesalamine to examine the effects of mesalamine on the metabolic risk factors associated with MetS.

METHODS

We performed a retrospective chart review using Cerner’s Health Facts (from July 2007 to July 2017). We identified UC patients with a MetS comorbidity and who were prescribed mesalamine within +/- 7 days of an encounter in which they were diagnosed with UC. We then collected the patient’s blood pressure, labs, and body measurement index (BMI) for each of these patient at the index date and the closest values to 12 months after the index date. We used analysis of covariance (ANCOVA) to determine the effect of mesalamine therapy in patients with both UC and MetS on the metabolic parameters after 12 months of treatment compared to baseline.

RESULTS

Our search of Cerner Health Facts identified 6,197 UC patients with concomitant MetS who were prescribed mesalamine. Of these individuals, 48% were female and 52% were male and within this cohort 88.3% received oral mesalamine and 11.7% received mesalamine via the rectal route. Oral mesalamine reduced fasting glucose levels and increased HDL cholesterol in these patients. C-reactive protein levels and erythrocyte sedimentation rate were also significantly reduced. Rectal mesalamine only reduced BMI. Further analysis revealed several MetS conditions risk factors were further improved when mesalamine was taken in the absence of medication for hypertension, hyperglycemia or dyslipidemia.

CONCLUSION

In a retrospective chart study of UC-MetS patients, we found oral mesalamine improved several metabolic parameters associated with MetS. Our findings suggest the PPAR agonist mesalamine that targets the gastrointestinal tract could prove beneficial in improving hypertension, hyperglycemia and dyslipidemia.
Emergency department admissions during COVID-19: explainable machine learning to characterise data drift and detect emergent health risks
Authors: Duckworth Christopher , Chmiel Francis P. , Burns Dan K. , Zlatev Zlatko D. , White Neil M. , Daniels Thomas W. V. , Kiuber Michael , Boniface Michael J.
Published: May 2021

Supervised machine learning algorithms deployed in acute healthcare settings use data describing historical episodes to predict clinical outcomes. Clinical settings are dynamic environments and the underlying data distributions characterising episodes can change with time (a phenomenon known as data drift), and so can the relationship between episode characteristics and associated clinical outcomes (so-called, concept drift). We demonstrate how explainable machine learning can be used to monitor data drift in a predictive model deployed within a hospital emergency department. We use the COVID-19 pandemic as an exemplar cause of data drift, which has brought a severe change in operational circumstances. We present a machine learning classifier trained using (pre-COVID-19) data, to identify patients at high risk of admission to hospital during an emergency department attendance. We evaluate our model’s performance on attendances occurring pre-pandemic (AUROC 0.856 95%CI [0.852, 0.859]) and during the COVID-19 pandemic (AUROC 0.826 95%CI [0.814, 0.837]). We demonstrate two benefits of explainable machine learning (SHAP) for models deployed in healthcare settings: (1) By tracking the variation in a feature’s SHAP value relative to its global importance, a complimentary measure of data drift is found which highlights the need to retrain a predictive model. (2) By observing the relative changes in feature importance emergent health risks can be identified.
Increased prevalence and clinical impact of hypocalcaemia in severe COVID-19 distinguishes it from other forms of infective pneumonia
Authors: Mehta Meera R , Ghani Hakim , Chua Felix , Draper Adrian , Calmonson Sam , Prabhakar Meghna , Shah Rijul , Navarra Alessio , Vaghela Tejal , Barlow Andrew , Vancheeswaran Rama
Published: May 2021

Background

Hypocalcaemia has been reported in the context of acute COVID-19, where it has been associated with an increased risk of hospitalisation and disease severity. Calcium is an important intracellular messenger that controls diverse cellular processes. Two other clinically important coronaviruses, SARS-CoV-1 and Middle East respiratory syndrome (MERS)-CoV, can use calcium ions to enter and replicate within host cells. Calcium may therefore be important in the pathophysiology of COVID-19 infection. We sought to investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity.

Methods

We conducted a single centre retrospective study of albumin-corrected serum calcium on adult patients with COVID-19 who presented between March 1stand May 16th2020. The primary outcome was maximal level of care based on the World Health Organization Clinical Progression Scale for COVID-19. Cases with community acquired pneumonia (CAP) and viral pneumonia (VP) were identified through a clinical database over three intervals (January to February 2018, January to February 2019 and September to December 2019).

Results

We analysed data from 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP. Hypocalcaemia (serum calcium <2.2mmol/L) was a specific and common clinical finding in patients with COVID-19 that was not present in other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with odds ratio of 2.33 for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by day 7-9 of admission, only in in survivors of COVID-19.

Conclusion

Hypocalcaemia may independently predict not only more severe but more progressive disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease. If calcium is ultimately shown to be critical to the entry and replication of SARS-CoV-2 in host cells, unravelling how this mechanism could be therapeutically targeted deserves more intensive examination.

Trial registration HRA

20/HRA/2344.
The indirect effect of mRNA-based Covid-19 vaccination on unvaccinated household members
Authors: Salo Jussipekka , Hägg Milla , Kortelainen Mika , Leino Tuija , Saxell Tanja , Siikanen Markku , Sääksvuori Lauri
Published: May 2021

Mass vaccination is effective in reducing SARS-CoV-2 infections among vaccinated individuals. However, it remains unclear how effectively Covid-19 vaccines prevent people from spreading the virus to their close contacts in real-world circumstances. Here, using nationwide administrative datasets on SARS-CoV-2 infections, vaccination records, demographics, and unique household IDs, we provide evidence about the direct and indirect effectiveness of Covid-19 vaccines in reducing infections among vaccinated individuals and their unvaccinated household members. Our estimates for adults imply indirect effectiveness of 8.7% (95% CI: -28.9 to 35.4) two weeks and 42.9% (95% CI: 22.3 to 58.1) 10 weeks after the first dose. We find that the indirect effect of Covid-19 vaccines is smaller and less precise for unvaccinated children aged between 3 to 18 years than for adults. These results provide household-level evidence that vaccines do not only protect vaccinated individuals but provide indirect protection to unvaccinated individuals in a real-world setting.
Modeling of the COVID-19 Cases in Gulf Cooperation Council (GCC) countries using ARIMA and MA-ARIMA models
Authors: Yagoub Rahamtalla , Eledum Hussein
Published: May 2021

Coronavirus disease 2019 (COVID-19) is still a great pandemic presently spreading all around the world. In Gulf Cooperation Council (GCC) countries, there were 1015269 COVID-19 confirmed cases, 969424 recovery cases, and 9328 deaths as of 30th Nov. 2020. This paper, therefore, subjected the daily reported COVID-19 cases of these three variables to some statistical models including classical ARIMA, kth SMA-ARIMA, kth WMA-ARIMA, and kth EWMA-ARIMA to study the trend and to provide the long-term forecasting of the confirmed, recovery, and death cases of the novel COVID-19 pandemic in the GCC countries. The data analyzed in this study covered the period starting from the first case of coronavirus reported in each GCC country to Nov 30, 2020. To compute the best parameter estimates, each model was fitted for 90% of the available data in each country, which is called the in-sample forecast or training data, and the remaining 10% was used for the out-of-sample forecast or testing model. The AIC was applied to the training data as a criterion method to select the best model. Furthermore, the statistical measure RMSE was utilized for testing data, and the model with the minimum AIC and minimum RMSE was selected. The main finding, in general, is that the two models WMA-ARIMA and EWMA-ARIMA, besides the cubic linear regression model have given better results for in-sample and out-of-sample forecasts than the classical ARIMA models in fitting the confirmed and recovery cases while the death cases haven’t specific models.
Non-pharmaceutical interventions and the emergence of pathogen variants
Authors: Ashby Ben , Smith Cameron A. , Thompson Robin N.
Published: May 2021

Abstract

Non-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, are important public health measures that can reduce pathogen transmission. In addition to playing a crucial role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply, restricting the availability of susceptible hosts, and altering the strength of selection for novel variants. Yet it is unclear how NPIs might affect the emergence of novel variants that are able to escape pre-existing immunity (partially or fully), are more transmissible, or cause greater mortality. We analyse a stochastic two-strain epidemiological model to determine how the strength and timing of NPIs affects the emergence of variants with similar or contrasting life-history characteristics to the wildtype. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross immunity to have a greater probability of emerging at intermediate levels of NPIs. This is because intermediate levels of NPIs allow an epidemic of the wildtype that is neither too small (facilitating high mutation supply), nor too large (leaving a large pool of susceptible hosts), to prevent a novel variant becoming established in the host population. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be implementation of strong, timely NPIs.
Minhee Analysis Package: An Integrated Software Package for Detection and Management of Spontaneous Synaptic Events
Authors: Kim Yong Gyu , Shin Jae Jin , Kim Sang Jeong
Published: May 2021

To understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.
RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells
Authors: Durand Sébastien , Bruelle Marion , Bourdelais Fleur , Bennychen Bigitha , Blin-Gonthier Juliana , Isaac Caroline , Huyghe Aurélia , Seyve Antoine , Vanbelle Christophe , Meyronet David , Catez Frédéric , Diaz Jean-Jacques , Lavial Fabrice , Ricci Emiliano P. , Ducray François , Gabut Mathieu
Published: May 2021

Embryonic stem cell (ESC) fate decisions are regulated by a complex molecular circuitry that requires tight and coordinated gene expression regulations at multiple levels from chromatin organization to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key regulatory pathways that efficiently control stem cell homeostasis. However, the molecular mechanisms underlying the regulation of these pathways remain largely unknown to date. Here, we analyzed the expression, in mouse ESCs, of over 300 genes involved in ribosome biogenesis and we identified RSL24D1 as the most differentially expressed between self-renewing and differentiated ESCs. RSL24D1 is highly expressed in multiple mouse pluripotent stem cell models and its expression profile is conserved in human ESCs. RSL24D1 is associated with nuclear pre-ribosomes and is required for the maturation and the synthesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors, including POU5F1 and NANOG, as well as components of the polycomb repressive complex 2 (PRC2). Consistently, RSL24D1 is required for mouse ESC self-renewal and proliferation. Taken together, we show that RSL24D1-dependant ribosome biogenesis is required to both sustain the expression of pluripotent transcriptional programs and silence developmental programs, which concertedly dictate ESC homeostasis.
A global dataset for the projected impacts of climate change on four major crops
Authors: Hasegawa Toshihiro , Wakatsuki Hitomi , Ju Hui , Vyas Shalika , Nelson Gerald C. , Farrell Aidan , Deryng Delphine , Meza Francisco , Makowski David
Published: May 2021

Reliable estimates of the impacts of climate change on crop production are critical for assessing the sustainability of food systems. Global, regional, and site-specific crop simulation studies have been conducted for nearly four decades, representing valuable sources of information for climate change impact assessments. However, the wealth of data produced by these studies has not been made publicly available. Here, we develop a global dataset by consolidating previously published meta-analyses and data collected through a new literature search covering recent crop simulations. The new global dataset builds on 8314 simulations from 203 studies published between 1984 and 2020. It contains projected yields of four major crops (maize, rice, soybean, and wheat) in 91 countries under major emission scenarios for the 21st century, with and without adaptation measures, along with geographical coordinates, current temperatures, local and global warming levels. This dataset provides a basis for a comprehensive understanding of the impacts of climate change on crop production and will facilitate the rapidly developing data-driven machine learning applications.