bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating paediatric hepatitis C prevalence in the United States
Authors: Rahal Harman , Boutros Sandra , Farhat Mohamad , Kullar Ravina , Rahal Kabir , Saab Sammy
Published: August 2020

Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates among women, given the assumption that most cases are vertically transmitted. Between 2001 and 2017, maternal HCV infection affected ~ 0.24% of all births, with prevalence increasing by at least 261%. On average, approximately 0.01% of the total number of live births were infected with HCV, with a 245% increase in the number of children born with the infection. HCV epidemiology has evolved, with women of childbearing age representing a greater proportion of infected individuals in the United States, and infants born to infected mothers being at risk. We therefore recommend a greater public health focus of HCV on the paediatric population.
Hepatitis A virus survival on drug paraphernalia
Authors: Medrzycki Magdalena , Kamili Saleem , Purdy Michael A.
Published: August 2020

The ongoing hepatitis A outbreaks in multiple states in the United States have concerned public health authorities since March 2017. The outbreaks have spread throughout 30 states and include primarily persons who use drugs, including persons who inject drugs (PWID) and persons experiencing homelessness. Contaminated drug injection paraphernalia and sharing of these items could potentially aid in transmission of hepatitis A virus (HAV) among these populations. We examined HAV survival on drug paraphernalia frequently shared among PWIDs. The effect of low pH on HAV survival using citric acid, which is frequently used by PWIDs during dose preparation, was investigated. We compared the plaque assay results with those concurrently obtained by qRT‐PCR to establish whether HAV RNA levels could be used as surrogates for plaque assay results. HAV suspended in minimal essential media at room temperature infected FRhK4 cells for more than 17 weeks. HAV remained viable in syringes/needles for up to 10 weeks depending on the gauge of the needles and the syringe dead volumes, and on cookers, tourniquets and cotton balls/filter surfaces for up to 4 weeks. HAV retained its infectivity for more than 10 weeks at pH as low as 2. In conclusion, our findings show that HAV survives and remains infective in or on injection drug use equipment for 1 to 10 weeks depending on the type of paraphernalia examined and environmental conditions. These findings suggest that contaminated drug paraphernalia can potentially facilitate the transmission of HAV within populations who share these items.
A noncanonical GATA transcription factor of Entamoeba histolytica modulates genes involved in phagocytosis
Authors: Huerta Miriam , Reyes Luz , García‐Rivera Guillermina , Bañuelos Cecilia , Betanzos Abigail , Díaz‐Hernández Mitzi , Galindo Ausencio , Bolaños Jeni , Cárdenas Helios , Azuara‐Liceaga Elisa , Chávez‐Munguía Bibiana , Orozco Esther
Published: August 2020

In this paper, we explored the presence of GATA in Entamoeba histolytica and their function as regulators of phagocytosis‐related genes. Bioinformatics analyses evidenced a single 579 bp sequence encoding for a protein (EhGATA), smaller than GATA factors of other organisms. EhGATA appeared phylogenetically close to Dictyostelium discoideum and Schistosoma mansoni GATA proteins. Its sequence predicts the presence of a zinc‐finger DNA binding domain and an AT‐Hook motif; it also has two nuclear localization signals. By transmission electron and confocal microscopy, anti‐EhGATA antibodies revealed the protein in the cytoplasm and nucleus, and 65% of nuclear signal was in the heterochromatin. EhGATA recombinant protein and trophozoites nuclear extracts bound to GATA‐DNA consensus sequence. By in silico scrutiny, 1,610 gene promoters containing GATA‐binding sequences appeared, including Ehadh and Ehvps32 promoters, whose genes participate in phagocytosis. Chromatin immunoprecipitation assays showed that EhGATA interact with Ehadh and Ehvps32 promoters. In EhGATA‐overexpressing trophozoites (NeoGATA), the Ehadh and Ehvps32 mRNAs amount was modified, strongly supporting that EhGATA could regulate their transcription. NeoGATA trophozoites exhibited rounded shapes, high proliferation rates, and diminished erythrophagocytosis. Our results provide new insights into the role of EhGATA as a noncanonical transcription factor, regulating genes associated with phagocytosis.
Electromagnetic interference effect of dental equipment on cardiac implantable electrical devices: A systematic review
Authors: Niu Yuting , Chen Yufei , Li Wenjing , Xie Ruiqin , Deng Xuliang
Published: August 2020

Background

The electromagnet interference (EMI) effect resulting from using dental equipment near cardiovascular implantable electronic devices (CIEDs) is controversial based on in vitro and in vivo studies. We aimed to summarize the available evidence to investigate the safety of using dental equipment on patients with CIEDs.

Methods

An electronic search was performed in PubMed, Embase, MEDLINE Ovid, and the Cochrane Library for relevant studies published between January 2000 and May 2020. The search strategy centered on terms related to dental devices and CIEDs. Two independent reviewers determined the final inclusion of the studies in the systematic review. The EMI effect was summarized based on different dental instruments detected in in vitro or in vivo studies.

Results

The primary search identified 84 articles, and 18 studies were finally included in this systematic review after exclusions. Most in vitro studies (n = 12) reported background noise or severe EMI affecting CIED function at a close distance from the lead tip or at a high sensitivity setting of CIEDs. In in vivo studies (n = 6), EMI that altered CIED function was not detected at clinical distance and sensitivity settings. The summary, based on electronic apex locators, ultrasonic devices, and electric pulp testers, demonstrated the compatibility of these common dental devices with CIEDs.

Conclusions

This systematic review indicates that most dental instruments can be used safely in routine dental practice. The EMI effect of dental equipment depends on the exposure distance and lead‐related parameters of the CIEDs.
Diagnostic concordance between pediatric emergency department physicians and dermatologists in a tertiary hospital in Mexico
Authors: Alba‐Rojas Erika L. , Morán‐Villaseñor Edna , Campos‐Cabrera Blanca L. , Aguirre‐Martínez Iliana L. , Vega‐Rangel Rosa V. , Cazares‐Ramírez Eduardo , Medina‐Vera Isabel , García‐Romero María Teresa
Published: August 2020

Background and Objectives

Skin diseases are a common reason for emergency department (ED) consultations; however, few studies have focused on pediatric patients. Diagnostic consistency between ED physicians and dermatologists varies from 43% to 58%, meaning many patients seeking emergency care may receive incorrect diagnoses and treatments. We aimed to determine the diagnostic concordance between ED physicians and pediatric dermatologists.

Methods

We conducted a prospective study including all pediatric patients (<18 years) who were seen for a skin condition at the ED from December 1, 2017, to June 1, 2018, and consented to participate. We classified diagnoses according to their etiology. Patients were diagnosed by ED trainees and attending physicians, followed by blinded pediatric dermatology trainees and attending physicians. We evaluated concordance using Fleiss's kappa coefficient (κ) with a 95% confidence interval. We further stratified the data by level of training.

Results

We included 185 patients. Inflammatory conditions were the most common reason for consultation, followed by infections; 10 patients required hospitalization. Concordance between diagnoses given at the ED and at the dermatology clinic was moderate (κ 0.472, 95% CI: 0.389‐0.455) with 62.7% agreement. Concordance between different diagnostic categories was lowest for autoimmune disorders and drug reactions (κ 0.392 with 95% CI: 0.248‐0.536 and κ 0.258 with 95% CI: 0.114‐0.402).

Conclusions

Diagnostic concordance between ED physicians and dermatologists was moderate and differed according to training level and diagnoses. Dermatological education for ED providers, specifically focusing on autoimmune disorders and drug reactions, may improve diagnostic accuracy and patient care.
Use of a T'LIFT transabdominal organ retraction device in two‐portal laparoscopic ovariectomy in dogs
Authors: Delaune Tiare , Matres‐Lorenzo Luis , Bernardé Antoine , Bernard Fabrice
Published: August 2020

Objective

To describe the use of the T'LIFT transabdominal organ retraction device to suspend ovaries during canine laparoscopic ovariectomy (LapOVE) and compare its use to a transabdominal suspension suture (TSS).

Design

Randomized clinical trial.

Animals

Client‐owned intact bitches (n = 30).

Methods

Dogs were randomly assigned either to group T, in which LapOVE was performed with the T'LIFT, or to group S, in which a TSS was used. Laparoscopic ovariectomy was performed by using a standard two‐portal protocol. Signalment (age, weight, body condition score [BCS], fat score of the ovarian pedicle [FSOP]), overall operative time, ovarian resection time, and perioperative complications were compared between groups.

Results

No significant differences were found between groups regarding age, weight, BCS, or FSOP. Surgical times were not significantly different between groups. No significant differences in major or minor complications were recorded. Overall operative time was significantly shorter for the last half of the cases compared with the first half, for the overall population, and within each group. Ovarian resection time for the last cases was significantly shorter compared with that for the first ones only in group T.

Conclusion

The T'LIFT was used to suspend ovaries for two‐portal LapOVE, with no major complications noted. There was no significant difference in surgical times or complications compared with transabdominal suturing.

Clinical significance

The T'LIFT can be considered as an alternative to transabdominal suture for ovarian suspension in dogs undergoing LapOVE.
Fake News Travels Fast: Exploring Misinformation Circulated Around Wu Lei’s Coronavirus Case
Authors: Li Bo , Scott Olan
Published: August 2020

This commentary analyzes how misinformation related to a coronavirus case of a star soccer player (i.e., Wu Lei) was spread widely on Chinese digital media and accepted by sports fans as the truth. The paper first examines the mechanisms by exploring how misinformation emerged and was disseminated. Then, the paper explores how social media and the fast-growing self-media in China exacerbate tendencies toward misinformation during the news production process, which poses a new threat to legacy media and journalists’ profession. The paper concludes by discussing new challenges faced by Chinese sports journalists in the new digital era after COVID-19.
Sports Television and the Continuing Search for Alternative Programming
Authors: Buehler Branden
Published: August 2020

The American sports television industry has scrambled to adjust to the loss of live sporting events in the wake of the coronavirus pandemic—a scramble clearly evidenced in programming schedules suddenly filled with replays of older event telecasts. However, rather than focusing on the apparent novelty of this type of substitute coronavirus programming, this article, instead, argues that the loss of live sporting events represents the amplification of a problem that television networks have already been grappling with for years: how to fill an ever greater number of outlets with sufficient year-round programming given a finite number of live events. With that in mind, this article proposes that many of the programming strategies that networks have turned to in the midst of the pandemic, including the expanded coverage of transactions (e.g., coverage of National Football League free agency) and the increased scheduling of documentaries (e.g., The Last Dance), have been familiar extensions of previously established alternative programming solutions.
Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization
Authors: Jia Jia , Jeon Eun Je , Li Mei , Richards Dylan J. , Lee Soojin , Jung Youngmee , Barrs Ryan W. , Coyle Robert , Li Xiaoyang , Chou James C. , Yost Michael J. , Gerecht Sharon , Cho Seung-Woo , Mei Ying
Published: August 2020

Motif analysis on evolutionarily conserved regions in laminin enabled the discovery of novel ligands for hydrogel development.
MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses
Authors: Bruchez Anna , Sha Ky , Johnson Joshua , Chen Li , Stefani Caroline , McConnell Hannah , Gaucherand Lea , Prins Rachel , Matreyek Kenneth A. , Hume Adam J. , Mühlberger Elke , Schmidt Emmett V. , Olinger Gene G. , Stuart Lynda M. , Lacy-Hulbert Adam
Published: August 2020

The CIITAdel keeps viruses at bay

A better understanding of cellular mechanisms involved in viral resistance is needed for the next generation of antiviral therapies. Bruchez
et al.
used a transposon-mediated gene-activation screen to search for previously unreported host restriction factors for Ebola virus (see the Perspective by Wells and Coyne). The authors found that a transcription factor, major histocompatibility complex class II transactivator (CIITA), induces resistance in human cell lines by directing the expression of the p41 isoform of the invariant chain (CD74). CD74 p41 then disrupts cathepsin-mediated Ebola glycoprotein processing, which prevents viral fusion and entry. CD74 p41 can also stymie the endosomal entry of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work should inform future treatments against cathepsin-dependent viruses such as filoviruses and coronaviruses. Additionally, the screening strategy used may serve as a blueprint for uncovering resistance mechanisms against other dangerous pathogens.

Science
, this issue p.
241
see also p.
167
Microbiota-modulated CART
+
enteric neurons autonomously regulate blood glucose
Authors: Muller Paul A. , Matheis Fanny , Schneeberger Marc , Kerner Zachary , Jové Veronica , Mucida Daniel
Published: August 2020

Metabolic signals from gut microbes

The gut is a stretchy, glandular, and highly innervated tube packed at its distal end with microorganisms. Disruption of the microbial community can lead to metabolic disorders such as obesity and diabetes. Muller
et al.
investigated how the microbiota interacts with the enteric nervous system to induce a metabolic outcome. A population of autonomous enteric neurons called CART
+
neurons are enriched in the ileum and colon, where most of the microbiota resides. Stimulation or ablation of the CART
+
neurons alters blood glucose levels, insulin, and feeding behavior. Furthermore, by manipulating the microbiota, the density of enteric neurons responds plastically in an inducible and reversible manner.

Science
, this issue p.
314
Improving Arsenic Tolerance of Pyrococcus furiosus by Heterologous Expression of a Respiratory Arsenate Reductase
Authors: Haja Dominik K. , Wu Chang-Hao , Ponomarenko Olena , Poole Farris L. , George Graham N. , Adams Michael W. W.
Published: August 2020

Arsenate respiratory reductases (Arr) are much less characterized than the detoxifying arsenate reductase system. The heterologous expression and characterization of an Arr from
Pyrobaculum aerophilum
in
Pyrococcus furiosus
provides new insights into the function of this enzyme. From
in vivo
studies, production of Arr not only enabled
P. furiosus
to use arsenate [As(V)] as a terminal electron acceptor, it also provided the organism with a higher resistance to arsenate and also, surprisingly, to arsenite [As(III)]. In contrast to the tungsten-containing oxidoreductase enzymes natively produced by
P. furiosus
, recombinant
P. aerophilum
Arr was much more active with molybdenum than with tungsten. It is also, to our knowledge, the only characterized Arr to be active with both molybdenum and tungsten in the active site.
Innovative approach to open abdomen: converting an enteroatmospheric fistula into an easily manageable stoma
Authors: Freund Michael Ron , Reissman Petachia , Spira Ram M , Topaz Moris
Published: August 2020

A 52-year-old super morbidly obese patient underwent elective laparoscopic conversion of a failed silastic ring vertical gastroplasty to a Roux-en-Y gastric bypass. Following surgery, she developed an anastomotic leak which required emergent laparotomy. The patient then suffered from a complex postoperative course during which she developed an intestinal fistula which freely drained into the wound and gradually led to its complete dehiscence. Her course was further complicated by the surfacing of an enteroatmospheric fistula. This devastating complication was managed by employing the TopClosure Tension Relief system. Using the inverse maturation technique, further described in this report, we were able to progressively approximate and invert the edges of the skin around the enteroatmospheric fistula, thereby facilitating its conversion to an easily manageable stoma. Using this technique, we were able to achieve delayed primary wound closure of a grade 4 open abdomen complicated by an enteroatmospheric fistula in just under 5 weeks’ time.
Denosumab-induced severe hypocalcaemia in a patient with vitamin D deficiency
Authors: Daga Natasha , Joseph Flavian
Published: August 2020

Postmenopausal women are at increased risk of osteoporosis. Osteoporotic fractures carry an increased risk of morbidity and mortality. Denosumab is a monoclonal antibody widely used for the treatment of osteoporosis by inhibiting osteoclast-induced bone resorption. Hypocalcaemia is a known side-effect of denosumab treatment. The majority of such cases have been described in patients with underlying metastatic cancer or chronic kidney disease. We present a patient who developed severe hypocalcaemia after administration of denosumab in the context of severe vitamin D deficiency and a normal kidney function. The management was further complicated by hypophosphatemia. Following replacement of vitamin D, the patient’s calcium and phosphate levels stabilised. The patient required intensive care monitoring for replacement of electrolytes. This case report emphasises the importance of screening and ongoing monitoring of risk factors for iatrogenic hypocalcaemia with denosumab treatment.
Adjuvant rituximab improves sensory ataxia in CIDP-related Sjögren syndrome
Authors: Rocha Raquel , Correia Filipe , Santos Andreia , Martins João
Published: August 2020

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune neuropathy characterised by insidious onset, progressive course, proximal and distal symmetrical weakness, and sensory impairment. It may affect patients of any age with varying degrees of clinical involvement and response rates to existing treatments. Sjögren syndrome (SS) is a systemic autoimmune disorder that primarily affects the exocrine glands causing a sicca syndrome. It may affect the peripheral nervous system, usually causing painful small fibre or pure sensory axonal neuropathy, ganglioneuronopathy or a predominantly sensory CIDP. We report the case of a 71-year-old man diagnosed with a debilitating and difficult-to-treat CIDP who, 5 years later, developed SS with pulmonary involvement. Due to lack of response to treatments other than periodic intravenous immunoglobulin (IVIg) every 12 days, we started adjuvant treatment with rituximab which increased the time interval between IVIg therapies by 50%, providing better quality of life for the patient.
Cardiac papillary fibroelastoma originating from the coumadin ridge and review of literature
Authors: Lak Hassan Mehmood , Kerndt Connor Charles , Unai Shinya , Maroo Anjli
Published: August 2020

Papillary fibroelastomas represent the second most common benign cardiac tumour, secondary only to cardiac myxoma. A majority of patients are asymptomatic on presentation. The most common clinical manifestations include stroke, transient ischaemic attack, myocardial infarction and angina. Echocardiography remains the primary imaging modality for identification of these tumours. The majority of papillary fibroelastomas arise from the valves. Simple surgical excision is the mainstay of treatment, carrying an excellent prognosis. We present an unusual case of cardiac papillary fibroelastoma originating from the coumadin ridge (CR) in a 70-year-old woman. The patient exhibited increasing paroxysms of her atrial fibrillation and was pursuing a MAZE procedure. Preoperatively, a transesophageal echocardiogram revealed a 0.7×1 cm intracardiac mass that had echocardiographic appearance of a fibroelastoma. Surgical resection and MAZE procedures were performed. The gross specimen and histopathology findings were consistent with papillary fibroelastoma. This case reports the seventh documented case of fibroelastoma originating from the CR.
Duplication cyst with midgut volvulus in a neonate: an unusual presentation
Authors: Pai Nitin G , Prabhu Santosh , Prabhakar Pavithra , Kumar Vijay
Published: August 2020

Incomplete intestinal fixation or malrotation of gut with midgut volvulus is one of the important causes of bilious vomiting in neonates. The incidence of malrotation of gut in population is 4% and that of duplication cyst is 1:4500. Patients with malrotation are prone to develop midgut volvulus due to their narrow mesenteric base demanding urgent surgical intervention. Common associated anomalies are intrinsic duodenal obstruction, internal hernias, caecal volvulus, anorectal malformations and Hirschsprung’s disease. The present case refers to a 4-day-old neonate who presented with malrotation of gut with reverse volvulus and an associated gastrointestinal duplication cyst, which is a rare association with only few reported case reports. After imaging with ultrasound and contrast radiograph, the baby underwent prompt surgical intervention in the form of Ladd’s procedure with resection and anastomosis of jejunal duplication cyst.
Novel approach to estimate tuberculosis transmission in primary care clinics in sub-Saharan Africa: protocol of a prospective study
Authors: Zürcher Kathrin , Morrow Carl , Riou Julien , Ballif Marie , Koch Anastasia Sideris , Bertschinger Simon , Liu Xin , Sharma Manuja , Middelkoop Keren , Warner Digby , Wood Robin , Egger Matthias , Fenner Lukas
Published: August 2020

Introduction

Tuberculosis (TB) transmission is difficult to measure, and its drivers are not well understood. The effectiveness of infection control measures at healthcare clinics and the most appropriate intervention strategies to interrupt transmission are unclear. We propose a novel approach using clinical, environmental and position-tracking data to study the risk of TB transmission at primary care clinics in TB and HIV high burden settings in sub-Saharan Africa.

Methods and analysis

We describe a novel and rapid study design to assess risk factors for airborne TB transmission at primary care clinics in high-burden settings. The study protocol combines a range of different measurements. We will collect anonymous data on the number of patients, waiting times and patient movements using video sensors. Also, we will collect acoustic sound recordings to determine the frequency and intensity of coughing. Environmental data will include indoor carbon dioxide levels (CO2 in parts per million) and relative humidity. We will also extract routinely collected clinical data from the clinic records. The number of Mycobacterium tuberculosis particles in the air will be ascertained from dried filter units using highly sensitive digital droplet PCR. We will calculate rebreathed air volume based on people density and CO2 levels and develop a mathematical model to estimate the risk of TB transmission. The mathematical model can then be used to estimate the effect of possible interventions such as separating patient flows or improving ventilation in reducing transmission. The feasibility of our approach was recently demonstrated in a pilot study in a primary care clinic in Cape Town, South Africa.

Ethics and dissemination

The study was approved by the University of Cape Town (HREC/REF no. 228/2019), the City of Cape Town (ID-8139) and the Ethics Committee of the Canton Bern (2019-02131), Switzerland. The results will be disseminated in international peer-reviewed journals.
Exploration of rural physicians’ lived experience of practising outside their usual scope of practice to provide access to essential medical care (clinical courage): an international phenomenological study
Authors: Konkin Jill , Grave Laura , Cockburn Ella , Couper Ian , Stewart Ruth Alison , Campbell David , Walters Lucie
Published: August 2020

Objectives

Rural doctors describe consistent pressure to provide extended care beyond the limits of their formal training in order to meet the needs of the patients and communities they serve. This study explored the lived experience of rural doctors when they practise outside their usual scope of practice to provide medical care for people who would otherwise not have access to essential clinical services.

Design

A hermeneutic phenomenological study.

Setting

An international rural medicine conference.

Participants

All doctors attending the conference who practised medicine in rural/remote areas in a predominantly English-speaking community were eligible to participate; 27 doctors were recruited.

Interventions

Semi-structured interviews were conducted. The transcripts were initially read and analysed by individual researchers before they were read aloud to the group to explore meanings more fully. Two researchers then reviewed the transcripts to develop the results section which was then rechecked by the broader group.

Primary outcome measure

An understanding of the lived experiences of clinical courage.

Results

Participants provided in-depth descriptions of experiences we have termedclinical courage. This phenomenon included the following features: Standing up to serve anybody and everybody in the community; Accepting uncertainty and persistently seeking to prepare; Deliberately understanding and marshalling resources in the context; Humbly seeking to know one’s own limits; Clearing the cognitive hurdle when something needs to be done for your patient; Collegial support to stand up again.

Conclusion

This study elucidated six features of the phenomenon ofclinical couragethrough the narratives of the lived experience of rural generalist doctors.
DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives
Authors: Perkhofer Lukas , Gout Johann , Roger Elodie , Kude de Almeida Fernando , Baptista Simões Carolina , Wiesmüller Lisa , Seufferlein Thomas , Kleger Alexander
Published: August 2020

Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homologous end joining and homologous recombination (HR). Defective HR, but also alterations in other DDR pathways, such asBRCA1,BRCA2,ATMandPALB2,occur frequently in both inherited and sporadic PDAC. Personalised treatment of pancreatic cancer is still in its infancy and predictive biomarkers are lacking. DDR deficiency might render a PDAC vulnerable to a potential new therapeutic intervention that increases the DNA damage load beyond a tolerable threshold, as for example, induced by poly (ADP-ribose) polymerase inhibitors. The Pancreas Cancer Olaparib Ongoing (POLO) trial, in which olaparib as a maintenance treatment improved progression-free survival compared with placebo after platinum-based induction chemotherapy in patients with PDAC and germlineBRCA1/2mutations, raised great hopes of a substantially improved outcome for this patient subgroup. This review summarises the relationship between DDR and PDAC, the prevalence and characteristics of DNA repair mutations and options for the clinical management of patients with PDAC and DNA repair deficiency.
Bayesian approach to interpreting somatic cancer sequencing data: a case in point
Authors: Yoon Ju-Yoon , Rosenbaum Jason N , Vergara Norge , Cohen Roger B , Wilson Robert B
Published: August 2020

Cancer lineage/tissue-of-origin assignment in cancers of unknown primary remains a challenge even when aided by massively parallel sequencing. The stakes are high for patients as many contemporary therapeutic strategies are disease-specific, and the biological differences can influence the patients’ responses. Herein, we provide an example of how Bayesian analysis can be used to merge data from clinical history, histology, immunohistochemistry (IHC) and cancer DNA sequencing to assist in tissue-of-origin assignment. Iterative Bayesian analysis is performed through a set of simple calculations to calculate the OR between the differential diagnoses. We illustrate a clinical case, where the distinction between a primary lung versus metastatic bladder cancer was aided meaningfully by iterative Bayesian analyses, incorporating IHC and sequencing data.
Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma
Authors: Ng Harry Ho Man , Lee Ren Yuan , Goh Siting , Tay Isabel Shu Ying , Lim Xinru , Lee Bernett , Chew Valerie , Li Huihua , Tan Benedict , Lim Sherlly , Lim Jeffrey Chun Tatt , Au Bijin , Loh Josh Jie Hua , Saraf Sahil , Connolly John Edward , Loh Tracy , Leow Wei Qiang , Lee Joycelyn Jie Xin , Toh Han Chong , Malavasi Fabio , Lee Ser Yee , Chow Pierce , Newell Evan W , Choo Su Pin , Tai David , Yeong Joe , Lim Tony Kiat Hon
Published: August 2020

Introduction

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality globally. Immune-checkpoint blockade (ICB) is one of the systemic therapy options for HCC. However, response rates remain low, necessitating robust predictive biomarkers. In the present study, we examined the expression of CD38, a molecule involved in the immunosuppressive adenosinergic pathway, on immune cells present in the tumor microenvironment. We then investigated the association between CD38 and ICB treatment outcomes in advanced HCC.

Methods

Clinically annotated samples from 49 patients with advanced HCC treated with ICB were analyzed for CD38 expression using immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF) and multiplex cytokine analysis.

Results

IHC and mIHC/IF analyses revealed that higher intratumoral CD38+cell proportion was strongly associated with improved response to ICB. The overall response rates to ICB was significantly higher among patients with high proportion of total CD38+cells compared with patients with low proportion (43.5% vs 3.9%, p=0.019). Higher responses seen among patients with a high intratumoral CD38+cell proportion translated to a longer median progression-free survival (mPFS, 8.21 months vs 1.64 months, p=0.0065) and median overall survival (mOS, 19.06 months vs 9.59 months, p=0.0295). Patients with high CD38+CD68+macrophage density had a better mOS of 34.43 months compared with 9.66 months in patients with low CD38+CD68+macrophage density. CD38himacrophages produce more interferon γ (IFN-γ) and related cytokines, which may explain its predictive value when treated with ICB.

Conclusions

A high proportion of CD38+cells, determined by IHC, predicts response to ICB and is associated with superior mPFS and OS in advanced HCC.
Deficits in verbal fluency in presymptomatic C9orf72 mutation gene carriers—a developmental disorder
Authors: Lulé Dorothée E , Müller Hans-Peter , Finsel Julia , Weydt Patrick , Knehr Antje , Winroth Ivar , Andersen Peter , Weishaupt Jochen , Uttner Ingo , Kassubek Jan , Ludolph Albert C
Published: August 2020

Background

A mutation in C9orf72 constitute a cross-link between amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). At clinical manifestation, both patient groups may present with either cognitive impairment of predominantly behaviour or language (in FTD) or motor dysfunctions (in ALS).

Methods

In total, 36 non-symptomatic mutation carriers from ALS or FTD families were examined, including 21 subjects with C9orf72 and 15 with SOD1 mutations. Data were compared with 91 age-matched, education-matched and gender-matched healthy subjects (56 were first-degree relatives from ALS or FTD families, 35 with no known family history of ALS/FTD). MRI scanning for diffusion tensor imaging was performed to map fractional anisotropy (FA). Subjects performed an extensive neuropsychological assessment to address verbal fluency, language, executive, memory and visuospatial function. Measurements were repeated after 12 months.

Results

C9orf72 expansion carriers performed significantly worse in verbal fluency and non-verbal memory and presented with distinct alterations in structural white matter integrity indicated by lower FA values in inferior and orbitofrontal cortical areas compared with carriers of SOD1 mutations or healthy subjects. Loss of structural integrity was associated with decreased verbal fluency performance. White matter alterations and cognitive performance showed no changes over 12 months in all subjects.

Discussion

Reduced verbal fluency performance seems to be a distinct clinical feature of C9orf72 carriers before symptomatic disease onset without evidence for change over time in our cohort. The results support the emerging hypothesis of a general disorder in development in addition to neurodegeneration in C9orf72 carriers.
Guillain-Barré syndrome in SARS-CoV-2 infection: an instant systematic review of the first six months of pandemic
Authors: Uncini Antonino , Vallat Jean-Michel , Jacobs Bart C
Published: August 2020

A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7–16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
Public knowledge of cardiovascular disease and response to acute cardiac events in three municipalities in Brazil
Authors: Bartlett Emily S , Flor Luisa S , Medeiros Danielle Souto , Colombara Danny V , Johanns Casey K , Camargo Vaz Fernando Antonio , Wilson Shelley , Duber Herbert C
Published: August 2020

Objective

To conduct a landscape assessment of public knowledge of cardiovascular disease risk factors and acute myocardial infarction symptoms, cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) awareness and training in three underserved communities in Brazil.

Methods

A cross-sectional, population-based survey of non-institutionalised adults age 30 or greater was conducted in three municipalities in Eastern Brazil. Data were analysed as survey-weighted percentages of the sampled populations.

Results

3035 surveys were completed. Overall, one-third of respondents was unable to identify at least one cardiovascular disease risk factor and 25% unable to identify at least one myocardial infarction symptom. A minority of respondents had received training in CPR or were able to identify an AED. Low levels of education and low socioeconomic status were consistent predictors of lower knowledge levels of cardiovascular disease risk factors, acute coronary syndrome symptoms and CPR and AED use.

Conclusions

In three municipalities in Eastern Brazil, overall public knowledge of cardiovascular disease risk factors and symptoms, as well as knowledge of appropriate CPR and AED use was low. Our findings indicate the need for interventions to improve public knowledge and response to acute cardiovascular events in Brazil as a first step towards improving health outcomes in this population. Significant heterogeneity in knowledge seen across sites and socioeconomic strata indicates a need to appropriately target such interventions.
Decline in stroke alerts and hospitalisations during the COVID-19 pandemic
Authors: Sharma Malveeka , Lioutas Vasileios-Arsenios , Madsen Tracy , Clark Judith , O'Sullivan Jillian , Elkind Mitchell S. V. , Willey Joshua Z. , Marshall Randolph S. , Selim Magdy H. , Greer David , Tirschwell David L. , Burton Tina , Boehme Amelia , Aparicio Hugo J.
Published: August 2020

Introduction

Patients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic. We investigated a decline in admissions for stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations.

Methods

We retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle. We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival.

Results

Compared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 (ptrend <0.001 for each). The declines coincided with state stay-at-home recommendations in late March. The greatest decline in hospital admissions was observed between 23 March and 19 April 2020, with a 31% decline compared with the corresponding weeks in 2019. Three of the five centres with 2019 and 2020 stroke alert data had a 46% decline in ED stroke alerts in late March and April 2020, compared with 2019. Median baseline NIHSS during these 4 weeks was 10 in 2020 and 7 in 2019. There was no difference in time from symptom onset to hospital arrival.

Conclusion

At these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic. There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data. Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke. Our findings underscore the indirect effects of this pandemic. Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis.
Drive-through testing for SARS-CoV-2 in symptomatic health and social care workers and household members: an observational cohort study
Authors: Parcell Benjamin J , Brechin Kathryn , Allstaff Sarah , Park Meg , Third Wendy , Bean Susan , Hind Chris , Farmer Rajiv , Chandler Daniel , Chalmers James D
Published: August 2020

The requirement for health and social care workers to self-isolate when they or their household contacts develop symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to critical staff shortages in the context of a pandemic. In this report, we describe the implementation of a drive-through testing service in a single National Health Service region in Scotland. From 17 March 2020 to 11 April 2020, 1890 SARS-CoV-2 reverse transcription PCR assay (RT-PCR) tests were performed. 22% of tests were positive. Allowing the remaining 78% of staff to return to work within 24 hours was estimated to save over 8000 working days during the peak pandemic period.
Exposure to health misinformation about COVID-19 and increased tobacco and alcohol use: a population-based survey in Hong Kong
Authors: Luk Tzu Tsun , Zhao Shengzhi , Weng Xue , Wong Janet Yuen-Ha , Wu Yongda Socrates , Ho Sai Yin , Lam Tai Hing , Wang Man Ping
Published: August 2020

Introduction

Health information about COVID-19 has been circulating in social networking sites, including unproven claims that smoking and alcohol drinking could protect against COVID-19. We examined if exposure to such claims was associated with changes in tobacco and alcohol consumption.

Methods

We conducted a population-based, landline and mobile phone survey of 1501 randomly sampled adults aged 18 years or older (47.5% male) in Hong Kong in April 2020. Respondents reported if they had ever seen claims that ‘smoking/alcohol drinking can protect against COVID-19’ from popular social networking platforms. Current tobacco and alcohol users reported if they had increased or reduced their consumption since the outbreak. Prevalence data were weighted by sex, age and education of the general adult population.

Results

19.0% (95% CI 16.8% to 21.4%) of all respondents reported having seen claims that ‘smoking/alcohol drinking can protect against COVID-19’ from social networking sites. Multinomial logistic regression showed that exposure to the claims was significantly associated with increased tobacco use (OR 2.37, 95% CI 1.08 to 5.20) in current tobacco users (N=280) and increased alcohol use (OR 4.16, 95% CI 2.00 to 8.67) in current drinkers (N=722), adjusting for sex, age, education level, alcohol/tobacco use status, home isolation, anxiety and depressive symptoms, and survey method.

Conclusion

Our results first showed that exposure to health misinformation that smoking/alcohol drinking can protect against COVID-19 was associated with self-reported increases in tobacco and alcohol consumption in Chinese during the pandemic.
Asymmetric Entrainment Structure of Pierce Oscillator Circuit
Authors: Ishimura Kazuyoshi , Inden Ryota , Komeno Naoto , Tokuda Isao T.
Published: August 2020

Experimental study is presented to uncover entrainment property of Pierce oscillator circuit (i.e., one of the most standard circuits for crystal oscillators) subject to sinusoidal external forcing. In contrast to the well-known Arnold tongues observed in a wide class of forced nonlinear systems, asymmetric shape was observed as an entrainment region of the circuit in two-dimensional parameter space spanned by the external forcing strength and frequency. Computation of the impedance curve revealed that the asymmetric shape is due to positive (inductive) or negative (capacitive) reactance of the Pierce circuit, which facilitates or inhibits the circuit oscillations. We extend this insight into two coupled Pierce circuits and show that, to efficiently achieve their synchronization, it is advantageous to drive a slow oscillator circuit by a fast circuit rather than to drive a fast circuit by a slow circuit. Our study provides a guideline on an optimal network configuration for coupled crystal oscillators, which may find applications in distributed digital clocks and wireless communication systems.
A Data-Driven Two-Stage Prediction Model for Train Primary-Delay Recovery Time
Authors: Gao Bowen , Ou Dongxiu , Dong Decun , Wu Yusen
Published: August 2020

Accurate prediction of train delay recovery is critical for railway incident management and providing passengers with accurate journey time. In this paper, a two-stage prediction model is proposed to predict the recovery time of train primary-delay based on the real records from High-Speed Railway (HSR). In Stage 1, two models are built to study the influence of feature space and model framework on the prediction accuracy of buffer time in each section or station. It is found that explicitly inputting the attribute features of stations and sections to the model, instead of implicit simulation, will improve the prediction accuracy effectively. For validation purpose, the proposed model has been compared with several alternative models, namely, Logistic Regression (LR), Artificial Neutral Network (ANN), Support Vector Machine (SVM) and Gradient Boosting Tree (GBT). The results show that its remarkable performance is better than other schemes. Specifically, when the error is extended to 3[Formula: see text]min, the proposed model can achieve up to the accuracy of 94.63%. It proves that our method has high value in practical engineering application. Considering the delay propagation of trains is a complex process, our future study will focus on building delay propagation knowledge base and dispatcher experience knowledge base.
The Turnout Abnormality Diagnosis Based on Semi-Supervised Learning Method
Authors: Shi Zeng Shu , Du Yiman , Du Tao , Shan Guochao
Published: August 2020

In China, the turnout abnormality very easily causes traffic accident or affects the efficiency due to the operating environment of railway transportation. The existing monitoring means are relatively backward, and mature automatic diagnosis method is lacking. In this study, a method based on semi-supervised learning algorithm for abnormal state diagnosis of turnout action curve is proposed, which is used to analyze and extract the electrical characteristics of the turnout by using the turnout action curve and the static and dynamic properties collected by the railway centralized monitoring system. The support vector machine model is used to construct the initial classifier with a small number of labeled samples, and the labeled samples are expanded from a large number of unlabeled samples. The switch curve is analyzed and diagnosed by using unlabeled data with a small amount of labeled data. The experimental results show that the method can automatically diagnose turnout electrical characteristics with high accuracy. While the cost of this method is relatively low compared with supervised learning, it can achieve higher accuracy and improve the practicability of fault diagnosis of turnout.