bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty in the Time of Corona
Authors: Jiwani Zishan , Cadwell Olivia G. , Parnes McKenna , Brown Adam D.
Published: January 2021

The recent COVID-19 pandemic is having profound impacts on every sector of society, and New York City (NYC) emerged as an early epicenter of the disease. Given the novelty and scale of the disease, information surrounding COVID-19 has been marked by considerable uncertainty and confusion. Although various factors have been associated with COVID-19 distress, little is known about the relations between levels of intolerance of uncertainty (IU) and anxiety symptoms and behaviors. This cross-sectional study sought to examine potential correlates and pathways between anxiety and precautionary behaviors with the two levels of IU: prospective and inhibitory. Individuals from NYC (N = 99) completed an online survey through Amazon Mechanical Turk. Findings revealed that fear of COVID-19 accounts for associations between prospective IU and greater anxiety symptoms and behaviors, whereas precaution adherence accounts for associations between prospective IU and reduced anxiety symptoms and behaviors. In addition, precaution adherence accounts for associations between inhibitory IU and greater anxiety symptoms and behaviors. The results shed light on ways in which variations in IU may be associated with anxiety symptoms and behaviors in the context of COVID-19 and future pandemic scenarios.
Impacts of Changing Sexual Behavior on Chlamydia and Gonorrhea Burden Among US High School Students, 2007 to 2017
Authors: Goodreau Steven M. , Pollock Emily D. , Wang Li Yan , Aslam Maria V. , Barrios Lisa C. , Dunville Richard L. , Rosenthal Elizabeth M. , Hamilton Deven T. , Katz David A. , Rosenberg Eli S.
Published: January 2021

Background

Rates of adolescent sexual activity have long been declining in the United States. We sought to estimate the number of cases of gonorrhea and chlamydia averted over 1 decade associated with these declines and associated costs saved.

Methods

We analyzed data from the Centers for Disease Control and Prevention's Youth Risk Behavior Survey of US high school students from 2007 to 2017 and combined it with epidemiological estimates drawn from the literature to parameterize a dynamic population transmission model. We compared transmissions from observed behavioral trends with a counterfactual scenario that assumed sexual behaviors from 2007 remained constant for 10 years. We calculated outcomes by age and for 3 racial/ethnic groups (Hispanic, non-Hispanic Black, and non-Hispanic White adolescents) who vary on underlying burden and amount of behavioral change.

Results

We estimated 1,118,483 cases of chlamydia and 214,762 cases of gonorrhea were averted (19.5% of burden across all ages). This yielded $474 million (2017 dollars) savings in medical costs over the decade. The largest number of averted cases (767,543) was among Black adolescents, but the largest proportion (28.7%) was among Hispanic adolescents.

Conclusions

Whatever its origins, changing sexual behavior among adolescents results in large estimated reductions in STI burden and medical costs relative to previous cohorts. Although diagnoses among adolescents have not declined at this rate, multiple explanations could make these apparently divergent trends consistent. Efforts to continue supporting effective sex education in and out of school along with STI screening for adolescents should reinforce these gains.
Syphilitic Spinal Disease: An Old Nemesis Revisited. A Case Series and Review of Literature
Authors: Koh Pei Xuan , Neo Shermyn Xiumin , Chiew Hui Jin , Singh Dinesh Rambachan , Saini Monica , Chen Zhiyong
Published: January 2021

Syphilitic spinal disease is a rare condition caused by the spirochete Treponema pallidum, either from direct spirochete involvement of the cord or as a consequence of indirect spirochete involvement of the meninges, blood vessels, or the vertebral column. After the introduction of penicillin therapy in the 1940s, it has become an increasingly rare condition. We report 3 challenging cases of syphilitic spinal disease presenting as myelopathy—1 with an extra-axial gumma of tertiary syphilis causing cord compression and 2 with tabes dorsalis complicated by tabetic spinal neuroarthropathy—each presenting a diagnostic dilemma to their treating physicians. We also review the literature for updates on modern investigative modalities and discuss pitfalls physicians need to avoid to arrive at the diagnosis.
Rapid Absolute Neutrophil Count Testing Guides Targeted Antimicrobial Therapy in Febrile Pediatric Oncology Patients
Authors: Gerber Nicole , Vella Adam , Racine-Brzostek Sabrina , Platt Shari L.
Published: January 2021

Objectives

It is well established that early antibiotic administration leads to improved outcomes in febrile neutropenic patients. To achieve this, many institutions administer empiric antibiotics to all febrile oncology patients in the emergency setting, before knowing their neutropenic status. This study evaluates the role of rapid absolute neutrophil count (ANC) testing in the targeted antimicrobial management of nonneutropenic febrile oncology patients.

Methods

We conducted a retrospective review of patients 19 years or younger presenting to the pediatric emergency service with an oncologic process and fever or history of fever. We examined the administration of antibiotics and outcomes in nonneutropenic patients.

Results

We included 101 patient encounters, representing 62 distinct patients. The rapid ANC test influenced antibiotic management in 94% (95/101) of patient encounters and resulted in no antibiotics or targeted antibiotic therapy in 88% (60/68) of nonneutropenic patients. Use of the rapid ANC test to guide treatment would have spared antibiotic administration in 68% (46/68) of well-appearing nonneutropenic patients with no alternate indication. No well-appearing, nonneutropenic patient had a positive blood culture, and only 1 required hospital admission on a repeat visit.

Conclusions

The rapid ANC is a useful tool to balance the goal of early antibiotic administration in febrile neutropenic oncology patients while promoting antibiotic stewardship in this vulnerable population.
Positron Emission Tomography Imaging of Programmed Death 1 Expression in Cancer Patients Using 124I-Labeled Toripalimab
Authors: Wang Shujing , Zhu Hua , Ding Jin , Wang Feng , Meng Xiangxi , Ding Lixin , Zhang Yan , Li Nan , Yao Sheng , Sheng Xinan , Yang Zhi
Published: January 2021

Purpose

Although anti–programmed cell death molecule-1 (PD-1)/PD-1 ligand therapy has achieved remarkable success in oncology field, the low response rate and lack of accurate prognostic biomarker identifying benefiting patients remain unresolved challenges. This study developed a PD-1 targeting radiotracer 124I-labeled toripalimab (124I-JS001) for clinical PET imaging and evaluated its biodistribution, safety, and dosimetry in human.

Methods

Patients with melanoma or urologic cancer confirmed by pathology were enrolled. 124I-JS001 PET/CT and PET/MR were performed with or without coinjection of 5 mg unlabeled JS001, and 18F-FDG PET was undertaken within 1 week.

Results

Eight melanoma and 3 urologic cancer patients were enrolled. No adverse events were noticed during the whole examination after the injection of 124I-JS001 and an acceptable dosimetry of 0.236 mSv/MBq was found. 124I-JS001 PET/CT showed high uptake in spleen and liver and slight uptake in bone marrow and lung. All primary and metastatic tumor lesions in 11 patients demonstrated different levels of uptake of 124I-JS001 with SUVmax ranging from 0.2 to 4.7. With coinjection of unlabeled JS001, the uptake in spleen was reduced significantly (P < 0.05), whereas tumor uptake and tumor background ratio increased significantly (P < 0.05). Four patients undertook regional 124I-JS001 PET/MR. All tumor lesions were detected effectively with abnormal MR signal on PET/MR, whereas PET/MR detected liver lesions more sensitively than PET/CT.

Conclusions

The first-in-human study demonstrated 124I-JS001 was a safe tracer for PET with acceptable dosimetry, and the PET/CT results showed a favorable biodistribution. PET/MR could detect liver lesions more sensitively than PET/CT.
Advancing the Specialty of Plastic Surgery While Helping and Supporting Other Surgical Services at an Academic Medical Center
Authors: Pu Lee L.Q. , Song Ping
Published: January 2021

While helping and supporting other surgical services at our academic medical center, we noticed that many clinical problems presented to our plastic surgery team are truly unique and challenging. Many of the necessary reconstructive procedures, performed by the senior author, had never been published in plastic surgery textbooks or the literature before. Because of the plastic surgeon's creative problem-solving ability, we use reconstructive treatment plans that also innovate and advance the field of plastic surgery. In this case series, we share our experience with creative solutions for the management of novel and challenging clinical problems faced by our plastic surgery service. The resultant and effective solutions for each challenging case have all been published in reputable plastic surgery journals by the senior author. Once published, our inventive reconstructive solutions can be harnessed by other plastic surgeons and trainees and new standardized techniques or solutions for these unique and challenging clinical problems can be established. Ultimately, plastic surgeons can evolve their specialty through helping and supporting other surgical services at an academic medical center by establishing innovative solutions for ever arising challenging clinical problems. Once again, the plastic surgery team in a tertiary hospital supports many surgical services so that more complex surgical procedures can be performed safely and complications from other surgical services can be managed successfully. Therefore, adequate support for a plastic surgery service, by the hospital or department, is critical in developing a strong plastic surgery program at an academic medical center.
Repair of Small-Size Wound With Achilles Tendon Exposure With Proximal Pedicled Cutaneous Neurovascular Flap
Authors: Yang Yun-fa , Gao Xiao-sheng , Liu Zai-li , Huang Jian-wen , Wang Jian-wei , Xu Zhong-he
Published: January 2021

Objective

To investigate the clinical outcomes associated with repairing of small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap in the dorsolateral foot.

Methods

After thorough debridement, 16 cases with small-sized wounds of Achilles tendon exposure were repaired by proximal pedicled cutaneous neurovascular flap of the dorsolateral foot, and their clinical outcomes were observed.

Results

All the flaps in the 16 cases survived completely, excluding the marginal part necrosis in 1 case, and all the wounds were healed. The 2-point discrimination of the flaps was 14.53 ± 1.55 mm (range, 12–17 mm) in patients without sural nerve injury after 3 to 18 months follow-up. No discomfort was felt in wearing normal shoes by all the 16 patients.

Conclusions

It is reasonable to repair the small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap of dorsolateral foot due to its effective repair of the wound, relatively uncomplicated surgery, and had satisfactory healing recovery.
Implementation of Distance-Based Simulation Training Programs for Healthcare Professionals
Authors: Vera Magdalena , Kattan Eduardo , Cerda Tomas , Niklitshek Jessie , Montaña Rodrigo , Varas Julian , Corvetto Marcia A.
Published: January 2021

Summary Statement

The sudden rise of critically ill patients secondary to the SARS-CoV-2 pandemic has triggered a surge in healthcare response. This project's goal was to provide essential cognitive and technical skills to healthcare professionals returning to the workforce or reassigned to critical care clinical duties during the COVID-19 pandemic. The plan included the implementation of 4 distance-based simulation training programs, with asynchronous personalized feedback. The courses allowed the acquisition of skills for the complete critical care patient management chain: use of personal protection equipment, use of a high-flow nasal cannula, endotracheal intubation, and prone positioning. Participants logged into the platform, reviewed material, practiced while recording the session, and uploaded the video through the training platform. The expert tutor remotely delivered asynchronous feedback. Participants trained remotely until achieving course approval. Remote-based simulation seems a feasible and attractive alternative to provide adequate educational solutions, especially for remote and rural areas.
Predicting Cognitive Impairment in Cerebrovascular Disease Using Spoken Discourse Production
Authors: Roberts Angela , Aveni Katharine , Basque Shalane , Orange Joseph B. , McLaughlin Paula , Ramirez Joel , Troyer Angela K. , Gutierrez Stephanie , Chen Angie , Bartha Robert , Binns Malcolm A. , Black Sandra E. , Casaubon Leanne K. , Dowlatshahi Dar , Hassan Ayman , Kwan Donna , Levine Brian , Mandzia Jennifer , Sahlas Demetrios J. , Scott Christopher J. M. , Strother Stephen , Sunderland Kelly M. , Symons Sean , Swartz Richard
Published: January 2021

Purpose:

Dementia due to cerebrovascular disease (CVD) is common. Detecting early cognitive decline in CVD is critical because addressing risk factors may slow or prevent dementia. This study used a multidomain discourse analysis approach to determine the spoken language signature of CVD-related cognitive impairment.

Method:

Spoken language and neuropsychological assessment data were collected prospectively from 157 participants with CVD as part of the Ontario Neurodegenerative Disease Research Initiative, a longitudinal, observational study of neurodegenerative disease. Participants were categorized as impaired (n = 92) or cognitively normal for age (n = 65) based on neuropsychology criteria. Spoken language samples were transcribed orthographically and annotated for 13 discourse features, across five domains. Discriminant function analyses were used to determine a minimum set of discourse variables, and their estimated weights, for maximizing diagnostic group separation.

Results:

The optimal discriminant function that included 10 of 13 discourse measures correctly classified 78.3% of original cases (69.4% cross-validated cases) with a sensitivity of 77.2% and specificity of 80.0%.

Conclusion:

Spoken discourse appears to be a sensitive measure for detecting cognitive impairment in CVD with measures of productivity, information content, and information efficiency heavily weighted in the final algorithm.
Augmenting Communicative Environments for People With Acquired Neurogenic Disorders
Authors: Hengst Julie A. , Sherrill Martha H.
Published: January 2021

This theoretical review article describes situated discourse analysis (SDA) and explores its implications for communication sciences and disorders. Drawing on situated theories of cognition and communication, SDA aims to understand real-time communicative processes of people engaging in complex sociocultural activities in specific sociomaterial environments. For SDA, discourse points first to the multimodal processes, not the products, of communicative interactions people engage in, and recognizes that these processes are fundamentally complex, distributed, and emergent. The article begins by defining SDA and describing four theoretical principles that guide this approach. We illustrate ways SDA might alter and advance theory, research, and clinical practice by considering its application to understanding the use of augmentative and alternative communication (AAC) technologies by adults with neurogenic communication disorders and their routine partners. We then explore empirical evidence from a methodologically diverse set of cases. The first considers Mialet's (2012) ethnographic study of Stephen Hawking and his use of AAC technologies, which highlights the complex, distributed, and emergent nature of situated discourse. We turn then to our clinical experiences, reflecting on what we have learned from our clients who have creatively repurposed technologies to remediate their activities and to mediate successful interactions and situated learning. Finally, we discuss a participatory design research project that used SDA as a guide for the innovative design of PIMs, pseudo-intelligent mediators (i.e., devices that sense the environment and act as active agents to mediate interactions). We conclude the article with a discussion of ways SDA contributes to and advances our research and clinical practice.
Neuropathic pain-induced cognitive dysfunction and down-regulation of neuronal pentraxin 2 in the cortex and hippocampus
Authors: Wang Rongguo , Man Yuanyuan , Zhou Meiyan , Zhu Yangzi , Wang Liwei , Yang Jianping
Published: January 2021

Evidence from both basic and clinical science suggests that neuropathic pain can induce cognitive dysfunction. However, these results are mainly based on a series of behavioral tests, there is a lack of quantitative variables to indicate cognitive impairment. Neuronal activity-regulated pentraxin (NPTX2) is a ubiquitously expressed, secreted protein in the nervous system. NPTX2 has been implicated to be involved in a variety of neuropathic diseases including Parkinson’s disease, ischemia, and Alzheimer’s disease. In a mouse model of chronic pain, NPTX2 is involved in the regulation of inflammatory responses. Here, we employ a variety of behavioral approaches to demonstrate that mice with chronic neuropathic pain have cognitive impairment and exhibit an increased anxiety response. The expression of NPTX2, but not NPTX1, was down-regulated in the hippocampus and cortex after chronic neuropathic pain exposure. The modulation effect of NPTX2 on cognitive function was also verified by behavioral tests using Nptx2 knock-out mice. Above all, we conclude that downregulation of NPTX2 induced by neuropathic pain may serve as an indicator of a progressive cognitive dysfunction during the induction and maintenance of spared nerve injury.
Predictors of discontinuation and hospitalization during long-acting injectable antipsychotic treatment in patients with schizophrenia spectrum disorder
Authors: Üçok Alp , Yağcioğlu Elif Anil , Aydin Memduha , Kara İlayda Arjen , Erbasan Vefa , Türkoğlu Özge , Ergün Simge , Chousein Mourat Giousouf , Oktar Nilgün , Uçar Nihat , Köroğlu Begüm Saba , Ozan Elif
Published: January 2021

The aim of this study was to evaluate discontinuation and hospitalization rates in patients with schizophrenia spectrum disorder who were treated with long-acting injectable (LAI) antipsychotics. We recorded clinical data about the period before the LAI treatment, when LAI treatment was initiated, and during the LAI treatment. Variables related to early (<8 weeks) and other LAI discontinuations and hospitalization were analyzed. Out of 452 patients, 14.4% of them discontinued their LAI treatment before 8 weeks, another 24.8% of the patients stopped their LAI by themselves later. Early discontinuers were younger, had shorter duration of illness, and less educated. Sixty-two (27.2%) of the patients were hospitalized under LAI treatment and 40% of the hospitalizations occurred in initial 6 months. Rate of hospitalization was 36.1% in the group who discontinued LAI after 8 weeks. In logistic regression analysis, younger age, history of combined antipsychotic treatment, number of hospitalizations before LAI, use of LAI for less than 6 months and alcohol abuse under LAI treatment were found related to hospitalization. Our findings suggested that discontinuation and hospitalization are still common among the patients who were treated with LAI antipsychotics.
Thiomicrorhabdus sediminis sp. nov. and Thiomicrorhabdus xiamenensis sp. nov., novel sulfur-oxidizing bacteria isolated from coastal sediments and an emended description of the genus Thiomicrorhabdus
Authors: Liu Xuewen , Chen Baoping , Lai Qiliang , Shao Zongze , Jiang Lijing
Published: January 2021

Two novel Gram-strain-negative and rod-shaped bacteria, designated strain G1T and G2T, were isolated from sediment samples collected from the coast of Xiamen, PR China. The cells were motile by a single polar flagellum. Growth of strain G1T occurred at 10–40 °C (optimum, 30 °C), at pH 6.0–9.0 (optimum, pH 7.5) and with 5–1530 mM NaCl (optimum, 510 mM), while the temperature, pH and NaCl concentration ranges for G2T were 4–45 °C (optimum, 28 °C), pH 5.5–8.0 (optimum, pH 6.5) and 85–1530 mM NaCl (optimum, 340 mM). The two isolates were obligate chemolithoautotrophs capable of using thiosulfate, sulfide, elemental sulphur or tetrathionate as an energy source. Strain G1T used molecular oxygen or nitrite as an electron acceptor, while strain G2T used molecular oxygen as the sole electron acceptor. The dominant fatty acids of G1T and G2T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16 : 0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The DNA G+C content of G1T and G2T were 45.1 and 48.3 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain G1T and G2T were members of the genus

Thiomicrorhabdus

, and most closely related to

Thiomicrorhabdus hydrogeniphila

MAS2T (96.0 %) and

Thiomicrorhabdus indica

13-15AT (95.4 %), respectively. The 16S rRNA gene sequence similarity between strains G1T and G2T was 95.8 %. Based on the phylogenetic, genomic and phenotypic data presented here, the isolate strains represent novel species of the genus

Thiomicrorhabdus

, for which the names Thiomicrorhabdus sediminis sp. nov. (type strain G1T=MCCC 1A14511T=KCTC 15841T) and Thiomicrorhabdus xiamenensis sp. nov. (type strain G2T=MCCC 1A14512T=KCTC 15842T) are proposed.
Streptomyces dysideae sp. nov., isolated from a marine Mediterranean sponge Dysidea tupha
Authors: Glaeser Stefanie P. , Rückert Christian , Abdelmohsen Usama Ramadan , Winkler Anika , Blom Jochen , Goesmann Alexander , Kalinowski Jörn , Hentschel Ute , Busse Hans-Jürgen , Kämpfer Peter
Published: January 2021

A Gram-stain-positive bacterium, strain RV15T, forming an extensively branched substrate mycelium and aerial hyphae that differentiate into spiral chains of spores, was isolated from a marine spongeDysidea tuphacollected from Rovinj (Croatia). Comparison of 16S rRNA gene sequences showed that strain RV15Tis a member of the genusStreptomyceswith highest sequence similarity to the type strains ofStreptomyces caeruleatus(98.8 %), Streptomyces cyaneochromogenes(98.6 %) andStreptomyces shaanxiensis(98.5 %). Sequence similarities to all otherStreptomycestypes strains were below 98.5 %. The multilocus sequence analysis-based evolutionary distance, the average nucleotide identity value and the genome-to-genome distance of strain RV15Tand the type strain ofS. caeruleatuswere clearly below the species cut-off values. Strain RV15Texhibited a quinone system composed of the major menaquinones MK-9(H4), MK-9(H6) and MK-9(H2), typical for the genusStreptomyces. The polar lipid profile of strain RV15Tconsisted of the predominant compounds diphosphatidylglycerol and phosphatidylethanolamine, moderate amounts of phosphatidylinositol, phosphatidylinositol mannoside, an unidentified lipid and an unidentified phospholipid. Major polyamines were spermine and spermidine. The diagnostic diaminoacid of the peptidoglycan wasmeso-diaminopimelic acid. The major fatty acids were iso C16 : 0, anteiso C17 : 1 ω9cand anteiso C17 : 0. The results of physiological and biochemical tests allowed further phenotypic differentiation of strain RV15Tfrom its most-related species and hence clearly merits species status. We propose the nameStreptomyces dysideaesp. nov. with the type strain RV15T(=DSM 42110T=LMG 27702T).
Association between COVID-19 mortality and population level health and socioeconomic indicators
Authors: Kandula Sasikiran , Shaman Jeffrey
Published: January 2021

With the availability of multiple COVID-19 vaccines and the predicted shortages in supply for the near future, it is necessary to allocate vaccines in a manner that minimizes severe outcomes. To date, vaccination strategies in the US have focused on individual characteristics such as age and occupation. In this study, we assess the utility of population-level health and socioeconomic indicators as additional criteria for geographical allocation of vaccines. Using spatial autoregressive models, we demonstrate that 43% of the variability in COVID-19 mortality in US counties can be explained by health/socioeconomic factors, adjusting for case rates. Of the indicators considered, prevalence of chronic kidney disease and proportion of population living in nursing homes were found to have the strongest association. In the context of vaccine rollout globally, our findings indicate that national and subnational estimates of burden of disease could be useful for minimizing COVID-19 mortality.
SNAI2-mediated direct repression ofBIMprotects rhabdomyosarcoma from ionizing radiation
Authors: Wang Long , Hensch Nicole R. , Bondra Kathryn , Sreenivas Prethish , Zhao Xiang Ru , Chen Jiangfei , Baxi Kunal , Campos Rodrigo Moreno , Gryder Berkley , Pomella Silvia , Rota Rossella , Chen Eleanor Y. , Khan Javed , Houghton Peter J. , Ignatius Myron S.
Published: January 2021

Ionizing radiation (IR) and chemotherapy are the mainstays of treatment for patients with rhabdomyosarcoma (RMS). Yet, the molecular mechanisms that underlie the success or failure of radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator of IR sensitivity in normal and malignant stem cells through its repression of the proapoptotic BH3-only genePUMA.Here, we demonstrate a clear correlation between SNAI2 expression levels and radiosensitivity across multiple RMS cell lines. Moreover, modulatingSNAI2levels in RMS cells through its overexpression or knockdown can alter radiosensitivityin vitroandin vivo.SNAI2 expression reliably promotes overall cell growth and inhibits mitochondrial apoptosis following exposure to IR, with either variable or minimal effects on differentiation and senescence, respectively. Importantly,SNAI2knockdown results in a striking increase in expression of the proapoptotic BH3-only geneBIM,and ChIP-seq experiments establish that SNAI2 is a direct repressor ofBIM.Since the P53 pathway is nonfunctional in the RMS cells used in this study, we have identified a new, P53-independent SNAI2/BIM axis that could potentially predict clinical responses to IR treatment and be exploited to improve RMS therapy.

Highlights

SNAI2 expression levels are directly correlated with protection from radiation in rhabdomyosarcoma.

Loss of SNAI2 primes rhabdomyosarcomas for IR-induced apoptosis.

SNAI2 directly represses the expression of the proapoptotic BH3-only geneBIM.
Stringency of the containment measures in response to COVID-19 inversely correlates with the overall disease occurrence over the epidemic wave
Authors: Mezencev R. , Klement C.
Published: January 2021

Non-pharmaceutical interventions (NPIs) were the only viable choice to mitigate or suppress transmission of COVID-19 in the absence of efficient and safe vaccines. Moreover, the importance of some NPIs is likely to remain in the future, at least in specific settings, in which the limited vaccination coverage and the high rate of contacts would enable further disease transmission. Nonetheless, the benefits of NPIs have been questioned with respect to their effectiveness and societal costs. In this study of 28 European countries during the first wave of epidemic we demonstrate a significant inverse correlation between the stringency of adopted containment measures and cumulative incidences of the confirmed COVID-19 cases. Our results indicate that early implementation of the stringent containment measures prior to detection of the first confirmed case, and rapid ramp-up of containment stringency after the first case was diagnosed, were instrumental for lowering the number of COVID-19 cases during the epidemic wave. The impact of delayed adoption of containment measures could not be fully attenuated by later adoption of even more stringent community containment.
Lumipulse G SARS-CoV-2 Ag Assay Evaluation for SARS-CoV-2 Antigen Detection Using 594 Nasopharyngeal Swab Samples from Different Testing Groups
Authors: Menchinelli Giulia , Bordi Licia , Liotti Flora Marzia , Palucci Ivana , Capobianchi Maria Rosaria , Sberna Giuseppe , Lalle Eleonora , Romano Lucio , Angelis Giulia De , Marchetti Simona , Sanguinetti Maurizio , Cattani Paola , Posteraro Brunella
Published: January 2021

Compared to RT-PCR, lower performance of antigen detection assays, including the Lumipulse G SARS-CoV-2 Ag assay, may depend on specific testing scenarios. We tested 594 nasopharyngeal swab samples from individuals with COVID-19 (RT-PCR cycle threshold [Ct] values ≤40) or non-COVID-19 (Ct values ≤40) diagnoses. RT-PCR positive samples were assigned to diagnostic, screening, or monitoring groups of testing. With a limit of detection of 1.2 × 104 SARS-CoV-2 RNA copies/ml, Lumipulse showed positive percent agreement (PPA) of 79.9% (155/194) and negative percent agreement of 99.3% (397/400), whereas PPAs were 100% for samples with Ct values of <18 or 18–<25 and 92.5% for samples with Ct values of 25–<30. By three groups, Lumipulse showed PPA of 87.0% (60/69), 81.1% (43/53), or 72.2% (52/72), respectively, whereas PPA was 100% for samples with Ct values of <18 or 18–<25, and was 94.4%, 80.0%, or 100% for samples with Ct values of 25–<30, respectively. RT-PCR positive samples were also tested for SARS-CoV-2 subgenomic RNA and, by three groups, testing showed that PPA was 63.8% (44/69), 62.3% (33/53), or 33.3% (24/72), respectively. PPAs dropped to 55.6%, 20.0%, or 41.7% for samples with Ct values of 25–<30, respectively. All 101 samples with a subgenomic RNA positive result had a Lumipulse assay’s antigen positive result, whereas only 54 (58.1%) of remaining 93 samples had a Lumipulse assay’s antigen positive result. In conclusion, Lumipulse assay was highly sensitive in samples with low RT-PCR Ct values, implying repeated testing to reduce consequences of false-negative results.
Efficacy and Safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients
Authors: Farrokhi Pegah , Sadeghi Alireza , sharifi Mehran , Dadvand Payam , Riechelmann Rachel , Moghaddas Azadeh
Published: January 2021

Purpose

This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.

Method

This retrospective cohort study(2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least two years. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint.

Results

Of included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank <0.001). FLOT regimen showed 84. 4% ORR, was notably higher than other groups (p-value<0. 01).

Conclusions

For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.
Left ventricular strain does not differentiate amyloidogenic profiles in at-risk individuals withTTRVal142Ile
Authors: Kontorovich Amy R. , Zhao Wenli , Gavalas Michael , Hashemi Helen , Liao Steve L. , Rashed Eman R. , Mitter Sumeet S. , Trivieri Maria Giovanna , Lerakis Stamatios , Kenny Eimear E. , Abul-Husn Noura S.
Published: January 2021

Objectives

To identify echocardiographic signatures featuring left ventricular longitudinal strain (LS) associated with genetic risk for cardiac amyloidosis (CA) due to theTTRVal142Ile (V142I) variant in African American (AA) and Hispanic/Latinx (H/L) individuals.

Background

Hereditary transthyretin amyloidosis (hATTR) can cause CA in ∼60-70% of older V142I carriers, but amyloid deposition progresses over many years. Disease-modifying therapy for CA is now available and early initiation is a priority for improving outcomes. Genomic screening programs and familial cascade genetic testing uncover pre-symptomatic V142I carriers, yet no guidelines exist for early CA detection.

Methods

Exome sequencing data linked to electronic health records (EHRs) of BioMebiobank participants were queried for AA or H/LTTR- andTTR+ (V142I) subjects without hATTR diagnoses and with prior echocardiograms suitable for retrospective LS analysis. Systemic “red flag” features of ATTR were extracted from EHRs ofTTR+ subjects. Speckle tracking echocardiography was retrospectively applied to determine global (GLS) and segmental LS. Relative apical sparing (RAS) was calculated.

Results

57TTR+ and 46TTR-age- and ancestry-matched subjects were included. GLS declined with age in females but not males, and was abnormal (<16%) in 18 (31.6%)TTR+ and 7 (15.2%)TTR-subjects (p = 0.066). Apical sparing was observed in 13 (22.8%)TTR+ and 11 (23.9%)TTR-subjects (p = 1.0). After adjusting for relevant demographic and echocardiographic covariates, neither GLS nor RAS was associated withTTR+ V142I status. Red flag features were not associated with GLS or RAS inTTR+ subjects.

Conclusions

Neither GLS nor RAS were significantly different betweenTTR+ andTTR-subjects. Since >50% ofTTR+ subjects were ≥ 60 years old, penetrance of CA by echocardiography among unselected V142I carriers may be lower than previously estimated. These findings indicate that surveillance for CA in individuals at increased genetic risk due to V142I should not rely solely on echocardiography, even with LS.
THE AIRBORNE CONTAGIOUSNESS OF RESPIRATORY VIRUSES: A COMPARATIVE ANALYSIS AND IMPLICATIONS FOR MITIGATION
Authors: Mikszewski A. , Stabile L. , Buonanno G. , Morawska L.
Published: January 2021

Background

The infectious emission rate is a critical input parameter for airborne contagion models, but data are limited due to reliance on estimates from chance superspreading events. A predictive estimation approach for the quanta emission rate (ERq) was recently proposed for SARS-CoV-2 using the droplet volume concentration of various expiratory activities. This study assesses the strength of the approach and uses novel predictive estimates of ERq to compare the contagiousness of respiratory pathogens.

Methods

We applied the predictive approach to SARS-CoV-1, SARS-CoV-2, MERS, measles virus, adenovirus, rhinovirus, coxsackievirus, seasonal influenza virus and Mycobacterium tuberculosis (TB) and compared ERq estimates to values reported in literature. We calculated infection risk in a prototypical classroom and barracks to assess the relative ability of ventilation to mitigate airborne transmission.

Results

Our median standing and speaking ERq estimate for SARS-CoV-2 (2.6 quanta hour (h)-1) is similar to active, untreated TB (3.1 h-1), higher than seasonal influenza (0.17 quanta h-1), and lower than measles virus (15 quanta h-1). We calculated event reproduction numbers above 1 for SARS-CoV-2, measles virus, and untreated TB in both the classroom and barracks for an activity level of standing and speaking at low, medium and high ventilation rates of 2.3, 6.6 and 14 liters per second per person, respectively.

Conclusions

Our predictive ERq estimates are consistent with the range of values reported over decades of research. In congregate settings, current ventilation standards are unlikely to control the spread of viruses with upper quartile ERq values above 10 quanta h-1, such as SARS-CoV-2, indicating the need for additional control measures.
In-silicoStructural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP40) of Marburg Virus: A Causative Agent of MAVD
Authors: Quazi Sameer , Golani Tanya , Akhta Nashat , Thomas Christina Elsa , Haider Zeshan
Published: January 2021

The Marburg virus (MARV) is reported to induce extreme hemorrhagic fever (MHF) with a high degree of infectivity and lethality in both human and non-human primates. An appropriate vaccination for this virus’s treatment is not yet usable, and thus needs intensive attempts on multiple scales. In this study, we employed the Computer-Aided Drug Design (CADD) based approach to identify the drug-like compounds inhibiting the replication of the Viral protein (VP40) of MARV. Our database search using an online database “PubChem” retrieved ∼3000 compounds structure-based similarity. Lipinski’s rule was applied to evaluate further the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with VP40 based on S-score (lower than reference Favipiravir inhibitor) and root-mean-square-deviation (RMSD) value (probably less than 2) using AutoDock 4.2. Resultantly, ∼100 compounds were identified having strong interaction with VP40 of MARV. After evaluating their binding energy using the AutoDock 4.2 software, four compounds (CID-67534452, CID-72201087, CID-123273976, CID-153708661) were identified that showed strongest binding energy with VP40 of MARV and strong inhibition effect than the Favipiravir. Robust binding energy, useful ADMET parameters and drug-likeness suggest that these candidates “CID-67534452, CID-72201087, CID-123273976, CID-153708661” have tremendous potential to stop the replication of MARV, hence might lead to the cure of MAVD.
Population Pharmacokinetics of Oxcarbazepine: A Systematic Review
Authors: Chen Yue-ting , Wang Chen-yu , Yin Yi-wei , Li Zi-ran , Lin Wei-wei , Zhu Min , Jiao Zheng
Published: January 2021

Introduction

Oxcarbazepine is commonly used as a first-line drug in the treatment of partial seizures. Due to the high pharmacokinetic variability of oxcarbazepine, many population pharmacokinetic models have been developed to optimise the dosing regimen of oxcarbazepine.

Areas covered

This review summarize the published population pharmacokinetic studies of oxcarbazepine in children and adults. The quality of the identified reports from the PubMed and Embase databases was also evaluated. We also explored the significant covariates that may have an impact on the dosage regimen and clinical use of oxcarbazepine.

Expert Opinion

The oxcarbazepine dose regimen was dependent on weight and co-administration with enzyme-inducing medications. In order to achieve more accurate treatment, we should establish PK / PD model of OXC to evaluate the effectiveness of dose adjustment from pharmacodynamic indicators. Furthermore, exploring the pharmacokinetic in specifical patients, such as infants is essential to improve its safety.

Article highlights

In this review, we identified weight, renal function, and co-administered medications as covariates that most likely to influence oxcarbazepine pharmacokinetics.

Comparing to adult patients, paediatric patients show a higher clearance per kilogramme weigh which lead to higher doses per kilogramme; they may also require therapeutic drug monitoring owing to a larger variation in clearance.

Further studies are essential to evaluate oxcarbazepine pharmacokinetics in special populations such as infants.
Passing the Test: A Model-based analysis of safe school-reopening strategies
Authors: Bilinski Alyssa , Salomon Joshua A. , Giardina John , Ciaranello Andrea , Fitzpatrick Meagan C.
Published: January 2021

Background

The COVID-19 pandemic has induced historic educational disruptions. In December 2020, at least two-thirds of US public school students were not attending full-time in-person education. The Biden Administration has expressed that reopening schools is a priority.

Objective

To compare risks of SARS-COV-2 transmission in schools across different school-based prevention strategies and levels of community transmission.

Design

We developed an agent-based network model to simulate transmission in elementary and high school communities, including home, school, and inter-household interactions.

Setting

We parameterized school structure based on average US classrooms, with elementary schools of 638 students and high schools of 1,451 students. We varied daily community incidence from 1 to 100 cases per 100,000 population.

Patients (or Participants)

We simulated students, faculty/staff, and adult household members.

Interventions

We evaluated isolation of symptomatic individuals, quarantine of an infected individual’s contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening.

Measurements

We projected transmission among students, staff and families during one month following introduction of a single infection into a school. We also calculated the number of infections expected for a typical 8-week quarter, contingent on community incidence rate.

Results

School transmission risk varies according to student age and community incidence and is substantially reduced with effective, consistent mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular, frequent testing due to the subclinical nature of most infections in children. Teacher vaccination can reduce transmission to staff, while asymptomatic screening both improves understanding of local circumstances and reduces transmission, facilitating five-day schedules at full classroom capacity.

Limitations

There is uncertainty about susceptibility and infectiousness of children and low precision regarding the effectiveness of specific prevention measures, particularly with emergence of new variants.

Conclusion

With controlled community transmission and moderate school-based prevention measures, elementary schools can open with few in-school transmissions, while high schools require more intensive mitigation. Asymptomatic screening should be a key component of school reopenings, allowing reopening at higher community incidence while still minimizing transmission risk.
Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria
Authors: Reiker Theresa , Golumbeanu Monica , Shattock Andrew , Burgert Lydia , Smith Thomas A. , Filippi Sarah , Cameron Ewan , Penny Melissa A.
Published: January 2021

Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We propose a using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability.
The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
Authors: Karlinsky Ariel , Kobak Dmitry
Published: January 2021

Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the expected mortality, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no global, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 94 countries and territories, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in several worst-affected countries (Peru, Ecuador, Bolivia, Mexico) the excess mortality was above 50% of the expected annual mortality. At the same time, in several other countries (Australia, New Zealand) mortality during the pandemic was below the usual level, presumably due to social distancing measures decreasing the non-COVID infectious mortality. Furthermore, we found that while many countries have been reporting the COVID-19 deaths very accurately, some countries have been substantially underreporting their COVID-19 deaths (e.g. Nicaragua, Russia, Uzbekistan), sometimes by two orders of magnitude (Tajikistan). Our results highlight the importance of open and rapid all-cause mortality reporting for pandemic monitoring.
Specific pattern of melanin-concentrating hormone (MCH) neuron degeneration in Alzheimer’s disease and possible clinical implications
Authors: Mladinov Mihovil , Oh Jun Yeop , Petersen Cathrine , Eser Rana , Li Song Hua , Theofilas Panos , Spina Salvatore , Seeley William W. , Bittencourt Jackson C. , Neylan Thomas C. , Grinberg Lea T.
Published: January 2021

Study Objectives

The lateral hypothalamic area (LHA) is one of the key regions orchestrating sleep and wake control. It is the site of wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons, which share a close anatomical and functional relation. The aim of the study was to investigate the degeneration of MCH neurons in Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), and relate the new findings to our previously reported pattern of degeneration of wake-promoting orexinergic neurons

Methods

Post-mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH- and tau-antibodies on formalin-fixed, celloidin embedded tissue was performed.

Results

There was no difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non-MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantlyhigherin AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons waslowerthan the proportion of tau+ non-MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p<0.001).

Conclusions

MCH neurons are more vulnerable to AD than PSP pathology. High burden of tau-inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD, contributing to wake-sleep disorders in AD. Further experimental research is needed to understand why MCH neurons are more resistant to tau-toxicity compared to orexinergic neurons.

STATEMENT OF SIGNIFICANCE

This is the first study to investigate the involvement of melanin-concentrating hormone (MCH) neurons in patients with Alzheimer’s disease and progressive supranuclear palsy. MCH neurons are key regulators of sleep and metabolic functions, and one of the major neuronal populations of the lateral hypothalamic area (LHA), but still underexplored in humans. Uncovering the pathology of this neuronal population in neurodegenerative disorders will improve our understanding of the complex neurobiology of the LHA and the interaction between MCH and orexinergic neurons. This new knowledge may open new strategies for treatment interventions. Further, this study represents a fundament for future research on MCH neurons and the LHA in tauopathies.