bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Resources for the Ex-Type ofPhytophthora citricola, and Well-Authenticated Isolates ofP. hibernalis,P. nicotianae, andP. syringae
Authors: Srivastava Subodh K. , Knight Leandra M. , Nakhla Mark , Abad Z. Gloria
Published: October 2021

Phytophthora is one of the most important genera of plant pathogens, with many members causing high economic losses worldwide. To build robust molecular identification systems, it is very important to have information from well-authenticated specimens and, in preference, the ex-type specimens. The reference genomes of well-authenticated specimens form a critical foundation for genetics, biological research, and diagnostic applications. In this study, we describe four draft Phytophthora genome resources for the ex-type of Phytophthora citricola BL34 (P0716 WPC) (118 contigs for 50 Mb), and well-authenticated specimens of P. syringae BL57G (P10330 WPC) (591 contigs for 75 Mb), P. hibernalis BL41G (P3822 WPC) (404 contigs for 84 Mb), and P. nicotianae BL162 (P6303 WPC) (3,984 contigs for 108 Mb) generated with MinION long-read high-throughput sequencing technology (Oxford Nanopore Technologies). Using the quality reads, we assembled high-coverage genomes of P. citricola with 291× coverage and 16,662 annotated genes; P. nicotianae with 205× coverage and 29,271 annotated genes; P. syringae with 76× coverage and 23,331 annotated genes, and P. hibernalis with 42× coverage and 21,762 annotated genes. With the availability of genome sequences and their annotations, we predict that these draft genomes will be accommodating for various basic and applied research, including diagnostics to protect global agriculture.
One Fictional Opioid Overdose in Eighteenth-century England and One Attempted Opioid Overdose in Nineteenth-century America
Authors: Frankenburg Frances R.
Published: October 2021

In today’s epidemic of opioid misuse, overdoses are not infrequent and can end in death. A fatal overdose is the culmination of a series of events that can be difficult to understand. Overdoses are not new, as is illustrated by two case reports from the past of overdoses on laudanum, a mixture of alcohol and opium. One was fictional and one was attempted, but they show how even 200 to 300 years ago people overdosed on opioids (or what they thought were opioids) when they found themselves in unbearable situations.
Operative Stabilization of Distal Radius Fractures Presenting With Ulnar Head Subluxation/Dislocation Addresses Distal Radioulnar Joint Instability Without Further Stabilization Procedures
Authors: Barger James , Lasa Santiago , Dell’Oca Alberto Fernandez , Jupiter Jesse
Published: October 2021

Objectives:

To determine the prevalence of ulnar head subluxation/dislocation in distal radius fracture and to discuss management, surgical outcomes, and relevant anatomy.

Setting:

Urban tertiary care hospital.

Patients/Participants:

Two hundred seventy-one patients with displaced distal radius fractures undergoing surgical management were reviewed to determine the incidence of ulnar head subluxation or dislocation using the Mino criteria defined by Mino et al.

Main Outcomes:

Postoperative computed tomography and radiographs were assessed for sigmoid notch and distal radioulnar joint (DRUJ) reduction and fracture healing. Range of motion, functional limitation, and pain were documented at final outcome.

Results:

Of the 271 cases, there were 8 cases of prereduction DRUJ subluxation/dislocation, including 2 frank dislocations and 6 subluxations (2.95%). All were treated with open reduction and internal fixation (ORIF) of the distal radius with a volar locked plate. In addition, 1 patient underwent ORIF of an associated distal ulnar shaft fracture and another, who had a grade 1 open fracture over the distal ulna, underwent open TFCC repair. The remaining 6 patients had closed reduction of the DRUJ without further stabilizing procedures. All had stable DRUJ joints following ORIF, both intra-operatively and at final follow-up. All ulnar heads were located within the DRUJ on post-op computed tomography; using the more sensitive radioulnar ratio there was residual ulnar head subluxation in 5/8 patients. Range of motion and functional outcome were excellent at an average of 133 weeks postoperatively. The DRUJ was stable at long-term follow-up in all patients.

Conclusions:

Ulnar head subluxation/dislocation is an uncommon injury in the setting of distal radius fracture. When present, it can usually be treated effectively with operative stabilization of the distal radius fracture without further stabilizing procedures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Avoid the In-Out-In Posterosuperior Femoral Neck Screw: The Use of the Piriformis Fossa Radiographic Landmark
Authors: Adams John D. (JD). , Walker J. Brock , Loeffler Markus
Published: October 2021

Objectives:

The most common screw placement across the femoral neck is the inverted triangle. The posterosuperior screw has a high incidence of cortical breach, creating an in-out-in (IOI) screw. This study examined the use of the radiographic landmark of the piriformis fossa (PF) to prevent screws being placed IOI. The hypothesis was that posterior screws placed below the PF inferior margin would prevent femoral neck cortex breach.

Methods:

Five bilateral cadaveric specimens were used to place 10 screws along the femoral neck posterosuperior cortex. On the AP view, 5 screws were placed in a traditional manner, below the femoral neck superior cortex but above the inferior margin of the PF (APF screws), and 5 were placed below the inferior margin of the PF (BPF). All 10 screws were placed inside the posterior cortex on the lateral view. After screw placement, each hip was dissected, and the femoral necks were evaluated for signs of cortical breach.

Results:

All screws placed below the PF inferior margin were contained within the femoral neck with no incidence of being IOI. All screws placed above the PF inferior margin breached the cortex to a varying degree. All screws were similar in relation to their distance from the posterior cortex on the lateral view, with the APF screws averaging 1.98 mm and the BPF screws averaging 1.82 mm (P value = 0.46).

Conclusions:

Placing the posterosuperior screw of the inverted triangle caudal to the PF inferior margin on the AP view seems to avoid cortical breach during percutaneous screw fixation of femoral neck fractures.
Percutaneous Reduction of Intra-Articular Posterior Wall Acetabular Rim Fragment: Surgical Technique and Case Series With an Average Follow-Up of 2 Years
Authors: Hadeed Michael M. , Parry Joshua A. , Stacey Stephen , Fader Ryan R. , Heare Austin , Mauffrey Cyril
Published: October 2021

Small posterior wall rim fractures are typically stable; however, if incarcerated in the joint, they must be removed. It is possible to reduce the morbidity associated with open approaches by addressing these incarcerated fragments in a percutaneous manner. This allows the restoration of joint congruity and removal of the osteochondral fragment from the joint space. The following report details the surgical technique to accomplish this, and the results of a case series of patients who underwent this technique. The advantages include limiting the morbidity of an open approach. However, the surgeon must be prepared to convert to an open approach if percutaneous removal does not accomplish the goals of surgery—a concentric, stable hip joint.
Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients
Authors: Block Jason M. , Madhok Jai , Owyang Clark G. , Merriman Kristen R. , Ruoss Stephen J. , Rao Vidya K.
Published: October 2021

OBJECTIVES:

Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients.

DESIGN:

Retrospective review and analysis.

SETTING:

Stanford University Hospital, a 605-bed tertiary care center.

PATIENTS:

Patients receiving inhaled epoprostenol in 2019.

INTERVENTIONS:

No interventions.

MEASUREMENTS AND MAIN RESULTS:

Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2–5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%).

CONCLUSIONS:

A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption’s requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.
Association of the Geriatric Nutritional Risk Index With the Survival of Patients With Non–Small Cell Lung Cancer After Nivolumab Therapy
Authors: Karayama Masato , Inoue Yusuke , Yoshimura Katsuhiro , Hozumi Hironao , Suzuki Yuzo , Furuhashi Kazuki , Fujisawa Tomoyuki , Enomoto Noriyuki , Nakamura Yutaro , Inui Naoki , Suda Takafumi
Published: October 2021

The nutritional status has the potential to affect cancer immunity. We evaluated the relationship between the nutritional status and the efficacy of nivolumab in patients with non–small cell lung cancer (NSCLC). This study was a post hoc analysis of a prospective, multicenter cohort study conducted at 14 institutions in Japan between July 2016 and December 2018. The Geriatric Nutritional Risk Index (GNRI), calculated from body weight and serum albumin, was evaluated in 158 patients with NSCLC who received nivolumab. GNRI was graded as low, moderate, and high. Low GNRI was associated with significantly shorter progression-free survival [median, 1.9 mo; 95% confidence interval (CI)=0.6–3.3 mo] than moderate (median, 4.0 mo; 95% CI=2.3–5.8 mo; P=0.017) and high GNRI (median, 3.0 mo; 95% CI=1.9–7.2 mo; P=0.014). Low GNRI was also linked to significantly shorter overall survival (OS) (median, 7.8 mo; 95% CI=2.6–12.0 mo) than moderate (median, 13.0 mo; 95% CI=9.6–15.2 mo; P=0.006) and high GNRI (median, 20.6 mo; 95% CI=15.6 mo–not reached; P<0.001). High GNRI was associated with significantly longer OS than moderate GNRI (P=0.015). In multivariate Cox proportional hazard analyses, increased GNRI was predictive of longer progression-free survival and OS, similarly as tumor programmed cell death-ligand 1 expression. In patients with NSCLC receiving nivolumab. GNRI was predictive of survival and may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.
Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV
Authors: Xia Huan , Huang Xiao-Jie , Hu Yue , Gao Li-Ying , Wu Yue , Wu Hao , Yan Zhong-Fang , Ma Ping
Published: October 2021

Background:

Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’ neuropsychiatric toxicity symptoms in a real-life setting.

Methods:

A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.

Results:

One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.

Conclusions:

The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
New Orthosis: The Thoracic Lumbar Sacral–Hip Spica Orthotic Sitting Frame
Authors: Okonski Temrah , Cabell Marlies Beerli
Published: October 2021

Introduction

This article describes the benefit of combining a thoracic lumbar sacral orthosis (TLSO) and a hip spica orthosis (HSO) to create a sitting frame for children with emerging neck and trunk control who cannot sit by themselves.

Materials and Methods

A child with motor disabilities who cannot sit independently benefits from a custom floor sitting frame. The sitting frame's thoracic lumbar sacral orthosis and hip spica orthosis are separate entities but are used together to allow a child to sit on the floor independently. Although the presented child does not need added head support, the TLSO-HSO sitting frame can be fabricated with cervical support. This sitting frame has a versatile joint allowing for movement between upright sitting and sitting with upper-limb weight bearing. The frame's hip joint can also be locked in different degrees of tilt. The described child uses the frame in a locked 90° upright position. Evaluation, fitting, fabrication, and reimbursement submission is explained.

Conclusions

Floor sitting is an important developmental milestone. Available equipment, such as floor sitters and compression garments intended to support a child in sitting, fail to sufficiently support all children with significant motor disabilities who have floor sitting goals. The TLSO-HSO sitting frame is a custom-made floor sitter that may give children with significant motor disabilities who have emerging neck and trunk control the support they need to independently sit on the floor. This orthosis has the potential to improve the lives of many children and their families as it can be used in both home and classroom settings and can give children with significant motor disabilities the opportunity to use their hands freely to play and to interact with peers during floor play time.

Clinical Relevance

Some children with severe motor disabilities cannot floor sit independently. The present study describes a new floor sitting frame that closes the gap between available products designed as these products do not meet the needs of all children with severe motor disabilities who have emerging neck and trunk control.
KCTD7-related progressive myoclonic epilepsy: report of three Indian families and review of literature
Authors: Narayanan Dhanya Lakshmi , Somashekar Puneeth H , Majethia Purvi , Shukla Anju
Published: October 2021

Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants inKCTD7, which encodes the BR-C,ttk and bab/pox virus and zinc finger domain-containing KCTD7 protein. We report four individuals from three Indian families presenting with an initial period of normal development, progressive myoclonic seizures followed by neuroregression and an abnormal electroencephalogram. We identified two novel missense variants, c.458G>C p.(Arg153Pro) and c.205C>G p.(Leu69Val) and one known disease-causing variant, c.280C>T p.(Arg94Trp) inKCTD7by exome sequencing. We review the literature of 67 individuals with variants inKCTD7. Our study expands the molecular spectrum ofKCTD7-related progressive myoclonic epilepsy.
Clonal hematopoiesis driven by DNMT3A and TET2 mutations: role in monocyte and macrophage biology and atherosclerotic cardiovascular disease
Authors: Cobo Isidoro , Tanaka Tiffany , Glass Christopher K. , Yeang Calvin
Published: October 2021

Purpose of review

Clonal hematopoiesis of indeterminate potential (CHIP), defined by the presence of somatic mutations in hematopoietic cells, is associated with advanced age and increased mortality due to cardiovascular disease. Gene mutations in DNMT3A and TET2 are the most frequently identified variants among patients with CHIP and provide selective advantage that spurs clonal expansion and myeloid skewing. Although DNMT3A and TET2 appear to have opposing enzymatic influence on DNA methylation, mounting data has characterized convergent inflammatory pathways, providing insights to how CHIP may mediate atherosclerotic cardiovascular disease (ASCVD).

Recent findings

We review a multitude of studies that characterize aberrant inflammatory signaling as result of DNMT3A and TET2 deficiency in monocytes and macrophages, immune cells with prominent roles in atherosclerosis. Although specific DNA methylation signatures associated with these known epigenetic regulators have been identified, many studies have also characterized diverse modulatory functions of DNTM3A and TET2 that urge cell and context-specific experimental studies to further define how DNMT3A and TET2 may nonenzymatically activate inflammatory pathways with clinically meaningful consequences.

CHIP, common in elderly individuals, provides an opportunity understand and potentially modify age-related chronic inflammatory ASCVD risk.
Social and Environmental Determinants of Health Among Family Caregivers of Older Adults
Authors: Savela Roosa-Maria , Nykänen Irma , Schwab Ursula , Välimäki Tarja
Published: October 2021

Background

Although the academic literature has focused on family caregivers’ health outcomes, little is known about the social and environmental determinants of health and the extent to which they relate to health disparities among family caregivers caring for older adults.

Objectives

The purpose of the study was to describe the prevalence of diseases and the association with social and environmental determinants of health among family caregivers caring for older adults in Finland.

Methods

A cross-sectional analysis was conducted. The study participants were interviewed on sociodemographic factors, comorbidity, and the World Health Organization Quality of Life Questionnaire. Independent-samples t-test, analysis of variance, and chi-square analyses were used to assess the social and environmental factors’ association with health outcomes.

Results

A total of 126 family caregivers participated in this study. The mean age of study participants was 74.4 years, and most were female, married, and from an urban area. Family caregivers’ older age and lower financial satisfaction were the main factors associated with the health inequalities. Older age was associated with age-related eye disorders, hearing impairment, coronary heart disease, and comorbidity. Family caregivers’ lower financial satisfaction was associated with diabetes, depression, and higher body mass index. Other factors linked to health disparities were family caregivers’ gender, educational attainment, and the municipality of living.

Discussion

This study provides evidence about family caregivers’ social and environmental determinants of health. To enhance health equity, nurse-led interventions, a life course approach, and intersectional actions are required.
Tattooing or Metallic Clip Placement? A Review of the Outcome Surrounding Preoperative Localization Methods in Minimally Invasive Anterior Resection Performed at a Single Center
Authors: Lin Chang-Lin , Chen Chou-Pin , Chiang Feng-Fan , Chen Chou-Chen , Chen Ming-Cheng , Chen Chih-Tien , Lin Chun-Yu , Cheng Hou-Hsuan , Shao Yen-Chen
Published: October 2021

Background:

For minimally invasive colorectal surgery, preoperative localization is a typical procedure. We here aimed to analyze compared 2 different localization methods in terms of short-term outcomes, like the operative outcome and postoperative complication rates based on real-world data.

Materials and Methods:

This was a retrospective analysis study conducted at a medical center. We enrolled patients who were presented with colonic tumor between January 1, 2016, and December 31, 2019, and they had undergone laparoscopic anterior resection in a single institution. Data included patient characteristics, operative outcome, length of hospital stay, and postoperative complications.

Results:

The preoperative localization group had a better resection margin (4 vs. 3 cm; P<0.001) and fewer procedures of intraoperative colonoscopy (4.67% vs. 18.22%; P=0.002). Lymph node harvest occurred more in patients with endoscopic tattooing procedures than with metallic clip procedures (25 vs. 20; P=0.031). No significant difference was found regarding postoperative complications and the length of hospital stay.

Conclusions:

Preoperative localization in a laparoscopic anterior resection led to better surgical planning and resection margin. The metallic clip placement was helpful in the preoperative localization and setting. The endoscopic tattooing method had a larger lymph node harvest and with fewer intraoperative colonoscopy.
Digital Cholangioscopy–assisted Nonradiation Endoscopic Retrograde Cholangiopancreatography for Retrieval of Common Bile Duct Stone
Authors: Feng Yadong , Xu Wei , Liu Yang , Sun Xiaomei , Liang Yan , Bu Chibin , Li Yuanyuan , Zhang Youyu , Zhang Jiong , Shi Ruihua
Published: October 2021

Background:

The use of nonradiation endoscopic retrograde cholangiopancreatography (NR-ERCP) for choledocholithiasis is still limited. Hereby, we introduced our experience of digital cholangioscopy (DCS)-assisted NR-ERCP for retrieval of common bile duct stones.

Methods:

Altogether, data of 132 patients who underwent DCS-assisted NR-ERCP for choledocholithiasis were collected. Procedure details, complications, and short-term follow-up were reviewed and analyzed and were compared with those of conventional endoscopic retrograde cholangiopancreatography (ERCP).

Results:

Routine stone extraction and laser lithotripsy were planned in 116 and 16 patients, respectively. Biliary access was successfully achieved by standard biliary cannulation and by advanced techniques in 99 and 33 patients, respectively. Complete stone removal was achieved in a single session in all patients. Routine stone extraction was performed in 117 patients, and laser lithotripsy was applied in 15 patients, among whom 14 patients with planned lithotripsy and 1 unexpected impacted stone found during the procedure. Unexpected right localized intrahepatic stones and purulent cholecystitis were found in 1 and 3 patients, respectively. Three mild and 1 moderate pancreatitis, 5 cases of hyperamylasemia, and 2 cases of leukocytosis occurred as complications. Short-term follow-up revealed no stone residual. Procedure details, technical success, and complications were not statistically different than conventional ERCP.

Conclusions:

DCS-assisted NR-ERCP is technically feasible, efficient, and safe for retrieval of common bile duct stones. This novel method is superior to conventional ERCP on detecting unexpected concomitant biliary diseases.
Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo
Authors: Al Shujairi Wisam-Hamzah , Kris Luke P. , van der Hoek Kylie , Cowell Evangeline , Bracho-Granado Gustavo , Woodgate Tahlia , Beard Michael R. , Carr Jillian M.
Published: October 2021

Viperin has antiviral function against many viruses, including dengue virus (DENV), when studied in cells in culture. Here, the antiviral actions of viperin were defined both in vitro and in a mouse in vivo model of DENV infection. Murine embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip−/−) showed enhanced DENV infection, accompanied by increased IFN-β and induction of ISGs; IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In contrast, subcutaneous challenge of immunocompetent WT and vip−/− mice with DENV did not result in enhanced infection. Intracranial infection with DENV resulted in body weight loss and neurological disease with a moderate increase in mortality in vip−/− compared with WT mice, although this was not accompanied by altered brain morphology, immune cell infiltration or DENV RNA level in the brain. Similarly, DENV induction of IFN-β, IFIT1, CXCL-10, IRF7 and TNF-α was not significantly different in WT and vip−/− mouse brain, although there was a modest but significant increase in DENV induction of IL-6 and IfI27la in the absence of viperin. NanoString nCounter analysis confirmed no significant difference in induction of a panel of inflammatory genes in WT compared to vip−/− DENV-infected mouse brains. Further, polyI:C stimulation of bone marrow-derived macrophages (BMDMs) induced TNF-α, IFN-β, IL-6 and Nos-2, but responses were not different in BMDMs generated from WT or vip−/− mice. Thus, while there is significant evidence of anti-DENV actions of viperin in some cell types in vitro, for DENV infection in vivo a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses.
Multicenter evaluation of the FilmArray Meningitis/Encephalitis assay in a routine setting
Authors: Maelegheer Karel , Reynders Marijke , Floré Katelijne , Vanacker Jos , Vanlaere Elke , Cartuyvels Reinoud , Raymaekers Marijke
Published: October 2021

Introduction.The FilmArray Meningitis/Encephalitis (FA-ME) Panel (Biofire, Salt Lake City, Utah, US) enables fast and automated detection of 14 pathogens in cerebrospinal fluid (CSF).

Gap statement.The performance of the FA-ME panel in a real routine setting has not yet been described and could lead to better patient management in cases of good performance.

Aim.This multicenter study verified the FA-ME panel analytical performance in a routine hospital setting.

Methodology.Between April 2016 and April 2018, 454 CSF samples were analysed with the FA-ME panel and compared with routine diagnostics. In cases of discrepancy or lack of a comparator result, a profound analysis based on patient records and other laboratory results was performed.

Results.A first analysis of 65 frozen samples, suspicious for meningitis had a 89 % concordance with routine diagnostics. The limit of detection (LOD) was confirmed for all pathogens except forStreptococcus agalactiaeand a strain ofHaemophilus influenzae (Escherichia coli K1andCryptococcus gattiiLOD experiments were not performed). The routine evaluation showed a positive result in 114 (25 %) clinical samples for at least one target. In three samples co-infections were found. After discrepancy analysis, overall sensitivity was 98 % (false negative FA-ME results for one HSV2, two HSV1 and two parechovirus). Four FA-ME results were considered false positive (two HHV6, one VZV and oneE. coli K1), resulting in an overall specificity of >99 %. A clinical added value of the assay was seen in the diagnosis of eight cases of bacterial meningitis.

Conclusion.Because of its rapidity and ease of use, the FA-ME panel has great potential in the diagnosis of central nervous infections. Implementation can improve clinical management, but costs and analytical limitations need to be addressed to convince clinicians and laboratories of its value.
Multi-locus sequence typing reveals genotypic similarity in Nigerian Cryptococcus neoformans AFLP1/VNI of environmental and clinical origin
Authors: Chidebelu Paul E. , Nweze Emeka I. , Meis Jacques F. , Cogliati Massimo , Hagen Ferry
Published: October 2021

Introduction

Pigeon droppings are among the major environmental sources of Cryptococcus neoformans AFLP1/VNI, from where the organism infects susceptible humans and animals resulting in cryptococcosis. Until now, C. neoformans AFLP1B/VNII was the only molecular type reported in Nigeria. Effective clinical treatment of this infection has occasionally been stymied by the emergence of antifungal non-susceptible, and resistant strains of C. neoformans AFLP1/VNI.

Hypothesis/Gap Statement

Pigeon droppings harbour C. neoformans and HIV/AIDS patients are among the susceptible population to develop cryptococcal infection. Epidemiological data on cryptococcal prevalence is limited in Nigeria.

Aim

To investigate the environmental prevalence of C. neoformans in South-eastern Nigeria and compare the isolates with other lineages by using molecular and microbiological tools.

Methodology

A total of 500 pigeon droppings and 300 blood samples of HIV/AIDS patients were collected, respectively, from five market squares and three tertiary healthcare centres within the Nsukka area of South-eastern Nigeria. The antifungal susceptibility of the C. neoformans isolates to amphotericin B, fluconazole, 5-fluorocytosine, itraconazole, voriconazole, posaconazole, and isavuconazole was investigated based on the CLSI M27-A3 protocol. Yeasts were identified by MALDI-TOF MS, thereafter Cryptococcus MLST was performed according to the International Society for Human and Animal Mycology (ISHAM) consensus scheme.

Results

C. neoformans was recovered from 6 (1.2 %) pigeon droppings and 6 (2 %) blood cultures of HIV/AIDS patients. Molecular analyses indicated that all cryptococcal isolates belong to serotype A and the AFLP1/VNI molecular type with sequence type (ST)32. Infection with C. neoformans was independent of sex and age of the patients investigated. All C. neoformans isolates were susceptible to the seven antifungal agents.

Conclusion

This is the first report on the prevalence of C. neoformans AFLP1/VNI (ST32) in environmental and clinical samples from Nigeria. The antifungal susceptibility indicates that antifungal resistance by C. neoformans is yet a rare occurrence in Nigeria.
Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY
Authors: Hulme William J , Williamson Elizabeth J , Green Amelia , Bhaskaran Krishnan , McDonald Helen I , Rentsch Christopher T , Schultze Anna , Tazare John , Curtis Helen J , Walker Alex J , Tomlinson Laurie , Palmer Tom , Horne Elsie , MacKenna Brian , Morton Caroline E , Mehrkar Amir , Fisher Louis , Bacon Seb , Evans Dave , Inglesby Peter , Hickman George , Davy Simon , Ward Tom , Croker Richard , Eggo Rosalind M , Wong Angel YS , Mathur Rohini , Wing Kevin , Forbes Harriet , Grint Daniel , Douglas Ian J , Evans Stephen JW , Smeeth Liam , Bates Chris , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , Sterne Jonathan AC , Hernán Miguel , Goldacre Ben
Published: October 2021

Objectives

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers.

Design

Cohort study, emulating a comparative effectiveness trial.

Setting

Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform.

Participants

317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable.

Interventions

Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out.

Main outcome measures

Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination.

Results

The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27).

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.
Differentiating COVID-19 and dengue from other febrile illnesses in co-epidemics: Development and internal validation of COVIDENGUE scores
Authors: Gérardin Patrick , Maillard Olivier , Bruneau Léa , Accot Frédéric , Legrand Florian , Poubeau Patrice , Manaquin Rodolphe , Andry Fanny , Bertolotti Antoine , Levin Cécile
Published: October 2021

Background

From a cohort study, we developed two scores to discriminate coronavirus 2019 (COVID-19) from dengue and other febrile illnesses (OFIs).

Methods

All subjects suspected of COVID-19 who attended the SARS-CoV-2 testing center of Saint-Pierre hospital, Reunion, between March 23 and May 10, 2020, were assessed for identifying predictors of both infectious diseases from a multinomial logistic regression model. Two scores were developed after weighting the odd ratios then validated by bootstrapping.

Results

Over 49 days, 80 COVID-19, 60 non-severe dengue and 872 OFIs were diagnosed. The translation of the best fit model yielded two scores composed of 11 criteria: contact with a COVID-19 positive case (+3 points for COVID-19; 0 point for dengue), return from travel abroad within 15 days (+3/-1), previous individual episode of dengue (+1/+3), active smoking (−3/0), body ache (0/+5), cough (0/-2), upper respiratory tract infection symptoms (−1/-1), anosmia (+7/-1), headache (0/+5), retro-orbital pain (−1/+5), and delayed presentation (>3 days) to hospital (+1/0). The area under the receiver operating characteristic curve was 0.79 (95%CI 0.76-0.82) for COVID-19 score and 0.88 (95%CI 0.85-0.90) for dengue score. Calibration was satisfactory for COVID-19 score and excellent for dengue score. For predicting COVID-19, sensitivity was 97% at the 0-point cut-off and specificity 99% at the 10-point cut-off. For predicting dengue, sensitivity was 97% at the 3-point cut-off and specificity 98% at the 11-point cut-off.

Conclusions

The COVIDENGUE scores proved discriminant to differentiate COVID-19 and dengue from OFIs in the context of SARS-CoV-2 testing center during a co-epidemic.
Medical genetics workforce in Brazil: practitioners, services, and disease distribution
Authors: Bonilla Carolina , Sortica Vinicius Albuquerque , Schuler-Faccini Lavinia , Matijasevich Alicia , Scheffer Mário C.
Published: October 2021

Purpose

In anticipation of the implementation of personalized medicine (PM) in Brazil we assessed the demographic characteristics of its medical genetics workforce together with the distribution of rare genetic diseases (RGD) and hereditary cancer syndromes (HCS) across municipalities in the country.

Methods

We used demographic data from an earlier report on medical specialties, and open databases providing summarized data on the public and private healthcare systems, for the years 2019 and 2020. In the public system we considered RGD live births and hospitalizations, and HCS mortality. In the private system we obtained data on RGD, HCS and genetic counselling appointments.

Results

The 332 registered medical geneticists (MGs) were mostly female, attended a public medical school, and were predominantly registered in the Southeast. The distribution of MGs overlapped the country-wise distribution of all types of genetic disease and service examined, indicating that ∼30% of the patient population has access to a MG specialist.

Conclusion

The Brazilian MG workforce is concentrated in the richest and most populated areas and while it covers a significant proportion of the population there are vast regions with very limited services. The public health system should address these inequalities for a successful transition to PM.
Persistence of antibody and T cell responses to the Sinopharm/BBIBP-CorV vaccine in Sri Lankan individuals
Authors: Jeewandara Chandima , Aberathna Inoka Sepali , Pushpakumara Pradeep Darshana , Kamaladasa Achala , Guruge Dinuka , Wijesinghe Ayesha , Gunasekera Banuri , Tanussiya Shyrar , Kuruppu Heshan , Ranasinghe Thushali , Dayarathne Shashika , Dissanayake Osanda , Gamalath Nayanathara , Ekanayake Dinithi , Jayamali Jeewantha , Jayathilaka Deshni , Dissanayake Madushika , Jayadas Tibutius Thanesh , Mudunkotuwa Anushika , Somathilake Gayasha , Harvie Michael , Nimasha Thashmi , Danasekara Saubhagya , Wijayamuni Ruwan , Schimanski Lisa , Rijal Pramila , Tan Tiong K. , Dong Tao , Townsend Alain , Ogg Graham S. , Malavige Gathsaurie Neelika
Published: October 2021

Background

To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals.

Methods

SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second dose of the vaccine. ACE2 receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays.

Results

193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. 14.3% to 16.7% individuals in the 20 to 39 age groups had detectable antibodies to the RBD of the WT and VOC, while the positivity rates of those >60 years of age was <10%. 14/49 (28.6%) had IFNγ ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined after 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40 to 59 (p=0.0007) and ≥60 (p=0.005) age groups.

Conclusions

Antibody responses declined in all age groups, especially in those >60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.
Applying Behavioral Nudges in a Dietary Comparator for Surgical Trials: Developing the MediDiet
Authors: Zhang Irene Y. , Norwitz Daniel , Drewnowski Adam , Agrawal Nidhi , Flum David R. , Liao Joshua M.
Published: October 2021

Introduction

The Mediterranean diet is being studied as an alternative to surgery for common gastrointestinal conditions. However, dietary change can be challenging. “Nudges” – behavioral science strategies seeking to influence cognitive processes to promote good behaviors – may help. We conducted a pilot study evaluating the acceptability of the MediDiet, a behaviorally designed dietary intervention incorporating nudges and recommendations based on the Mediterranean Diet.

Methods

We conducted a three-phase pilot study involving parallel randomized surveys of U.S. adults. After completing a validated questionnaire assessing dietary consistency with a Mediterranean diet, participants were randomized to feedback containing no nudge versus nudge: peer comparison; peer comparison + positive affect induction; or default. Participants then rated their positive and negative emotions, motivation for dietary change, and interest in recipes. Responses were analyzed using baseline covariate-adjusted regression.

Results

Among 1,709 participants, 56% were men, 73% were White, and the mean age was 38. In response to dietary feedback, participants reported low negative emotions, high positive emotions, moderate motivation for dietary change and high interest in recipes. Nudges did not affect the extent of negative (p=0.104) or positive (p=0.34) emotions, motivation (p=0.139), or interest (p=0.86). In exploratory analyses, those with moderate and high consistency with the Mediterranean diet, with or without nudges, reported lower negative affect, greater positive affect, greater motivation, and greater interest in recipes, than the minimally consistent, no nudge group.

Conclusion

Delivering dietary feedback based on the Mediterranean diet using behavioral nudges was acceptable among U.S. adults, rousing positive reactions without triggering negative ones. As early evidence, this pilot study provides the basis for testing nudge-based dietary guidance among individuals with symptomatic gallstones, diverticulitis, and other gastrointestinal diseases.

Highlights

The MediDiet is being developed as a novel, behaviorally designed dietary intervention for the non-operative management of common gastrointestinal conditions including symptomatic gallstones and diverticulitis, classically managed with surgery.

In this exploratory pilot study, delivering dietary feedback based on the Mediterranean diet using behavioral nudges was acceptable among U.S. adults.

This foundational work will help serve as the basis for testing nudge-based dietary guidance among individuals with symptomatic gallstones, diverticulitis, and other gastrointestinal diseases, and ultimately conducting clinical trials to compare dietary interventions to surgical management for these conditions.
Fetal brain growth and infant autistic traits
Authors: Aydin Ezra , Tsompanidis Alex , Chaplin Daren , Hawkes Rebecca , Allison Carrie , Hackett Gerald , Austin Topun , Padaigaitė Eglė , Gabis Lidia V. , Sucking John , Holt Rosemary , Baron-Cohen Simon
Published: October 2021

Background

Research indicates that structural differences exist in the brains of individuals who later display developmental conditions (e.g., autism). To date only a handful of studies have explored the relationship between fetal brain growth and later infant outcomes, with a particular focus on fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. We investigate whether fetal brain measurements correlate with the emergence of autistic traits in toddlers.

Method

219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. A 2D ultrasound was performed at 12-, 20- and between 26-30-weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). 178 infants were subsequently followed up at 18-20 months of age and completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT) to observe early autistic traits.

Results

HC was larger in males than in females in both the second and third trimester. There was a significant positive association between TCD size at 20 weeks and Q-CHAT scores at 18-20 months of age, found in both univariate and multivariate analyses, and this remained significant after controlling for sex.

Conclusion

There is a positive relationship between cerebellar (TCD) development at 20 weeks’ gestation and the later emergence of autistic traits (at 18-20 months of age). Atypical neurodevelopment may start prenatally. If replicated these findings could facilities early diagnosis and improved outcomes.