bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical therapeutic effects of combined methotrexate and other chemotherapeutic agents in treating children and young patients with osteosarcoma
Authors: Peng Cheng , Ren Zhinan , Zhu Jian , Zhang Panke , Cao Shuyan , Hao Yingjie
Published: April 2021

Background:

Osteosarcoma is one of the most common primary bone tumour in children and young patients, and the third most common among adults. Its main treatment option is currently based on neoadjuvant or adjuvant chemoradiotherapy along with the lesion's surgical resection. The current study's primary aim is to examine the clinical therapeutic impacts of combined methotrexate, along with other chemotherapeutic agents to treat children and young adults suffering from osteosarcoma.

Methods:

We will perform a comprehensive literature search in English database (PubMed, EMBASE, Cochran Library CINAHL, and PsycINFO) and Chinese database (Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database, and WanFang Database) with no language restriction from their inception to the search date. Additionally, two independent authors will screen the works of literature obtained from these databases, obtain information, and examine the risks of data included for the studies’ bias. Furthermore, we intend to employ the Q statistics as well as I
2 statistics to calculate heterogeneity among each study's analysis. Accordingly, we will utilize the funnel plots and Egger test to assess the possibility of publication bias where relevant.

Results:

The current study aims to provide significant information regarding the clinical therapeutic impacts of combines methotrexate along with other chemotherapeutic agents to treat children and young adults suffering from osteosarcoma.

Conclusions:

The present study will generate compelling evidence of combined methotrexate as well as other chemotherapeutic agents for osteosarcoma among children and young adults. Also, it will provide clinical practice suggestions.

Ethics and dissemination:

The study is founded upon published data. Therefore, there is no requirement for ethics approval.

OSF registration number:

March 26, 2021.osf.io/a23rc. (https://osf.io/a23rc/)
Risk factors for post-traumatic stress disorder in acute trauma patients
Authors: Tang Furong , Tan Jianghong , Guo Xi , Huang Jinlian , Yi Jinhua , Wang Lang
Published: April 2021

Background:

Post-traumatic stress disorder (PTSD) is one of the most commonly reported mental health consequences, followed by disasters and traumatic events, either natural or man-made. At present, there are no unified results for the prevalence rate of PTSD in patients suffering from acute trauma and related influencing factors. Therefore, the purpose of this study is to systematically evaluate the existing literatures, thus obtaining a comprehensive estimation of the combined prevalence rate of PTSD and related factors in trauma patients, so as to provide evidence support for clinical disease prediction models and intervention strategies.

Methods:

Published articles will be retrieved from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Research reports will be searched in March 2021. STATA 14.0 software will be applied for data analysis. Mantel–Haenszel fixed effect model or DerSimonian–Laird random effect model will be selected to estimate the pooled prevalence of PTSD in patients with acute trauma and associated factors.

Results:

We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.

Conclusions:

The results of this analysis can be used to establish a risk prediction model of PTSD in patients experiencing acute trauma, so as to provide intervention strategies.

OSF Registration Number:

DOI 10.17605/OSF.IO/Z275U.
Effect of a confirmatory testing algorithm on early acute HIV diagnosis in Korea
Authors: Wang Jin-Sook , Sim Hyo-Jung , Park Su-Jin , Park Gye-Ryeng , Kang Chun , Chung Yoon-Seok
Published: April 2021

The 17 Provincial Institutes of Health and Environment (PIHEs) in Korea use HIV antibody, antigen, and Western blot assays for confirmatory testing of HIV infection. The Korea Disease Control and Prevention Agency (KDCA) has further included p24 antigen neutralization and nucleic acid tests (NATs) since 2015. Our study aimed to investigate the effect of this new testing algorithm on the confirmation rate of HIV infection.

Annual changes, from 2012 through 2017, in positive or indeterminate HIV confirmatory results were compared for the two algorithms between the PIHEs and the KDCA. Fiebig stages and Western blot p31 band were used to identify the diagnostic proportions of acute or early chronic HIV for the two algorithms.

The number of positive cases in the samples requested from PIHEs for reconfirmation by the KDCA has steadily increased from 10.3% in 2014 to 33.3% in 2017. However, the number of indeterminate cases dropped sharply, from 71.9% in 2014 to 14.0% in 2017. The results for the p31 reactive band were 27.4% and 88.4% for the KDCA and PIHEs, respectively. Of positive cases reported by the KDCA, 22.9% were in the early acute stage and Fiebig stages I to II.

The new testing algorithm has improved the diagnosis of HIV infections in the early acute stage. Early confirmatory diagnosis can prevent secondary transmission of HIV and provide early treatment opportunities for people living with HIV infection.
Clinical study on acupuncture treatment of hypertension with hyperactivity of liver yang
Authors: Wu Jiaojuan , Zhang Xudong , Zhao Jiping , Xue Yanjun , Yu Pengcheng , Wu Xiaoli , Liu Qingguo
Published: April 2021

Introduction:

Hypertension can lead to different degrees complications of cardiovascular and cerebrovascular, and increase the risk of sudden death. Acupuncture has become a complementary alternative therapy for hypertension because of its antihypertensive and nontoxic side effects. However, there is still lack of evidence-based medicine evidence for an effective acupuncture antihypertensive prescription. The purpose of this study is to evaluate the effect of a special acupuncture prescription on hypertension with hyperactivity of liver yang.

Methods:

In this randomized controlled trial, we will recruit 56 hypertensive patients with hyperactivity of liver yang. Then the patients will be randomly divided into control group and experimental group. The control group will be treated with western medicine, and the experimental group will be treated with medicine combined with acupuncture. The intervention will last 4 weeks. The indices will be collected before acupuncture, after acupuncture, and 2 weeks after acupuncture. The primary outcome will be 24-hour ambulatory blood pressure. The secondary outcomes will be clinic blood pressure, anxiety and depression score, and the syndrome score of hyperactivity of liver yang. The auxiliary indicators will be blood pressure load values and salt sensitivity risk rate. The exploratory indicator will be acupoint diagnosis. The safety evaluation indicator will be incidence of adverse events.

Discussion:

The results of this study will provide favorable evidence for the efficacy and safety of acupuncture in reducing blood pressure, and explore the positive reaction acupoints which related to hypertension.
Effectiveness and acceptability of myoinositol in prevention of gestational diabetes mellitus
Authors: Wang Li , Cheng Hong , Wang Xue , Zheng Linmei
Published: April 2021

Background:

The existing meta-analyses and randomized studies on myoinositol are of poor quality, with small sample sizes, and involve a homogeneous population. The general applicability of these findings to the National Health Service is unclear. We thus conduct this new high-quality systematic review and meta-analysis to assess the efficacy and safety of myoinositol in pregnant woman.

Methods:

The study protocol will be developed and executed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. All of the following inclusion criteria in the PICOS order will be met by the studies included in our meta-analysis:

The following electronic databases will be searched: PubMed, Scopus, EMBASE, and Cochrane Library databases. The Cochrane risk of bias tool will be used to evaluate the risk of bias of the included randomized trials by 2 independent reviewers.

Results:

We will perform a meta-analysis using standard techniques for the outcomes.

Conclusions:

It was hypothesized that myoinositol supplementation could increase the action of endogenous insulin and prevent GDM and its complications.

Trial registration:

10.17605/OSF.IO/9W8DV.
Cold scissors versus electrosurgery for hysteroscopic adhesiolysis
Authors: Yang Liuqing , Wang Ling , Chen Yun , Guo Xiaoshi , Miao Chenyun , Zhao Ying , Li Lu , Zhang Qin
Published: April 2021

Background:

Intrauterine adhesion seriously affects reproductive health in women. Hysteroscopic adhesiolysis using cold scissors or electrosurgery is the main treatment, although there is no consensus on the preferable method. This review aimed to compare the efficacy and safety of these methods for treating moderate to severe intrauterine adhesion.

Methods:

PubMed, EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure were searched on April 30, 2020. Randomized controlled trials and observational studies that were published in all languages (must contain English abstracts) and compared hysteroscopic cold scissors with electrosurgery for the treatment of intrauterine adhesion were included. Mean differences, odds ratios, and 95% confidence intervals (CIs) were reported. Bias was evaluated using the Cochrane Risk of Bias assessment tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Data were analyzed using RevMan software (Review Manager version 5.3, The Cochrane Collaboration, 2014). Two researchers independently extracted data and assessed the quality of the included studies. If a consensus was not reached, a third researcher was consulted.

Results:

Nine studies (n = 761; 6 randomized controlled trials and 3 retrospective studies) were included. The intrauterine adhesion recurrence rate with second look hysteroscopy was significantly lower (odds ratio = 0.30, 95% CI = 0.16–0.56; P = .0002) with hysteroscopic cold scissors than with electrosurgery. The total operation time was significantly shorter (mean difference = –7.78, 95% confidence interval = –8.50 to –7.07; P < .00001), intraoperative blood loss was significantly lower (mean difference = –9.88, 95% CI = –11.25 to –8.51; P < .00001), and the menstrual flow rate was significantly higher (odds ratio = 4.36, 95% confidence interval = 2.56–7.43; P < .00001) with hysteroscopic cold scissors than with electrosurgery. There were no significant differences in the pregnancy rate. One complication (1 perforation case, hysteroscopic cold scissors group) was reported.

Conclusions:

Hysteroscopic cold scissors is more efficient in preventing intrauterine adhesion recurrence, increasing the menstrual flow, reducing intraoperative blood loss, and shortening the operation time.
Clinical therapeutic effects of trastuzumab in HER2-positive breast cancer patients
Authors: Tong Chuanming , Wang Chuan , Yang Kun
Published: April 2021

Background:

Despite the developments in diagnosis and treatment of HER2-positive metastatic breast cancer, there is a high likelihood in the development of resistance to trastuzumab. In general, HER2-positive patients with deteriorated health face negative clinical outcomes. The present study is conducted to systematically explore the medicinal properties of trastuzumab in HER2-positive breast cancer patients.

Methods:

Randomized controlled trials investigating the clinical properties of including trastuzumab to treat HER2-positive breast cancer cases will be sourced by exploring these online-based databases: MEDLINE, BIOSIS, China National Knowledge Infrastructure (CNKI), Cochrane Library, EMBASE, Central Register of Controlled Trials, and WanFang. Two independent authors will screen the literature, gather data, and assess the quality of selected studies. The significance of the relationship between the medical properties of trastuzumab when incorporated to treat HER2-positive breast cancer cases will be evaluated according to the relative risk, mean differences or standardized mean differences, and 95% confidence interval.

Results:

The outcomes from this review shall be issued in a journal that will be reviewed by peers.

Conclusion:

The conclusions presented in this review will serve as a reference for clinical practitioners and scholars to determine whether trastuzumab is an effective and safety intervention for treating HER2-positive breast cancer patients.

Ethics and dissemination:

Since this study is a systematic review of published studies, an ethical approval is not needed.

Systematic review registration number:

March 31, 2021.osf.io/wvqkf (https://osf.io/wvqkf/).
Primary vaginal malignant melanoma
Authors: Guo Na , Zhang Jiawen
Published: April 2021

Rationale:

Primary vaginal malignant melanoma is a sporadic and very aggressive tumor that is treated through surgery or radiotherapy combined with chemotherapy. Since most cases are diagnosed at an advanced stage, the operation range is extensive, the quality of life is poor, and the prognosis is gloomy.

Patient concerns:

A 58-year-old woman presented irregular water-like leukorrhea for 1 month after 6 years of menopause. Positron emission tomography-computed tomography revealed a 3.1 × 2.6 × 3.2 mass on the middle and lower part of the right vaginal wall. A gynecological examination revealed a 2 to 3 cm exophytic black mass in the lower-right part of the vaginal orifice. This mass was 2 cm from the urethral orifice. Furthermore, the mucosa of the anterior inferior vaginal wall had blackened and thickened, and there were some scattered black dots at the medial labia minora.

Diagnosis:

Due to the patient's symptoms with radiographic findings, the postmenopausal woman was diagnosed with primary vaginal malignant melanoma.

Interventions:

Surgery was done to remove the mass. The patient also underwent inguinal lymph node dissection, received immunotherapy, and was treated with nivolumab.

Outcomes:

After a 6-month follow-up period, the patient underwent a routine gynecological examination with negative radiological results. Moreover, no local recurrence or distant metastases were found.

Lessons:

This patient showed a good response to immunotherapy. With this treatment method, the prognosis is better for advanced-stage women, especially those who cannot endure the surgery. Local lesion resection and inguinal lymph node dissection combined with immunotherapy are recommended. The case reported here may help treat similar clinical cases.
Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis
Authors: Yang Jing , Du Jichen , Zhao Jing , Liu Haichao , Zhang Lvming , Cai Lina , Wang Qi , Han Bailin , Cui Jiangbo
Published: April 2021

Introduction

: Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disorder, frequently accompanied by the presence of neoplasms, comprising a spectrum of paraneoplastic syndrome.

Patient concerns:

A 56-year-old man was admitted for deterioration in memory and aberrant psychological behaviors, which lasted for at least 20 days

Diagnosis:

The patient was diagnosed as anti-AMPAR encephalitis and 4 months later, he was diagnosed with small cell lung cancer.

Interventions:

Once diagnosis for anti-AMPAR encephalitis was confirmed, methylprednisolone was prescribed with initial dose 500 mg/d for 14 days until the patient returned to pre-illness state. Then he was discharged with oral treatment with corticosteroids. Following the diagnosis of small cell lung cancer, he received 5 rounds of chemotherapy, including carboplatin and etoposide.

Outcomes:

After taken the prescription of Methylprednisolone for anti-AMPAR encephalitis, he returned to pre-illness state and was discharged. In April 21, 2017, after symptoms of respiratory system showed up, he was diagnosed with small cell lung cancer and he eventually died of respiratory failure.

Conclusion:

Though progress has been made in recent years in diagnosis and treatment for autoimmune encephalitis, it is challenging to diagnose due to the similarity in clinical findings with other autoimmune or infectious encephalitis. In addition, it is necessary for these patients to regularly have tumor screening, considering AMPAR antibody encephalitis is closely associated with neoplasm, and the incidence of paraneoplastic syndrome is 63% to 70%.
Transient infantile hypertriglyceridemia with jaundice
Authors: Wang Jun , Sun Fang , Xu Pengfei , Zhang Yufeng , Sun Xinrong , Deng Huiling
Published: April 2021

Rationale:

Transient infantile hypertriglyceridemia (HTGTI) is a rare autosomal recessive inherited disease caused by inactivating mutations in the glycerol-3-phosphate dehydrogenase 1 gene. To date, only a few patients have been reported worldwide. The symptoms of the affected individuals present a certain degree of transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis in early infancy. However, the clinical characteristics and pathogenesis of this disease are remain unclear.

Patient concerns:

A one month and twenty-five days old girl was admitted to hospital because of persisted jaundice and hepatomegaly for fifty days.

Diagnose:

The girl was diagnosed with HTGTI coincident with a noval mutation in glycerol-3-phosphate dehydrogenase 1.

Intervention:

She was advised to take low-fat diet and supplement of medium-chain fatty acids.

Outcomes:

Her jaundice was gradually normal at the age of 4 months without any treatment, and hypertriglyceridemia were normal at the age of 13 months, but still had elevated transaminases and hepatic steatosis.

Lessons:

Jaundice may be a novel phenotype in HTGTI. The report contributes to the expansion of HTGTI's gene mutation spectrum and its clinical manifestations.
Postoperative new-onset atrial fibrillation causing acute embolic occlusion of the superior mesenteric artery
Authors: Cho Jinbeom , Lee Dosang
Published: April 2021

Rationale:

Postoperative atrial fibrillation following noncardiac surgery increases mortality, length of hospital stay, and medical expenses; moreover, compared to nonvalvular atrial fibrillation, it poses a similar risk of thromboembolic complications. In this report, we discuss our decision-making process for diagnosis and treatment in case with unexpected postoperative new-onset atrial fibrillation causing acute mesenteric ischemia.

Patient concerns:

A 78-year-old male patient received varicose vein stripping and ligation in his right leg. The patient was previously healthy with no known comorbidities. The next day after surgery, he complained of sudden epigastric pain unresponsive to conservative treatment, and new-onset atrial fibrillation was observed on electrocardiography.

Diagnoses:

An abdominal computed tomography scan revealed acute embolic occlusion of the superior mesenteric artery

Interventions:

Emergent surgical embolectomy was performed successfully. The time to operation from the recognition of abdominal pain was 6 h. Surgical critical care was performed for life-threatening ischemic reperfusion injury.

Outcomes:

The patient was discharged from the hospital on the 40th postoperative day.

Lessons:

Atypical postoperative abdominal pain unresponsive to conservative treatment should be considered a surgical emergency, and a high level of clinical suspicion for acute mesenteric ischemia is required. Preoperative electrocardiography and postoperative telemetry might be helpful in some asymptomatic patients.
Dual-construct fixation is recommended in ipsilateral femoral neck fractures with infra-isthmus shaft fracture
Authors: Wei Yi Ping , Lin Kai Cheng
Published: April 2021

The aim of this study was to evaluate the risk factors related to osteosynthesis failure in patients with concomitant ipsilateral femoral neck and shaft fractures, including old age; smoking habit; comminuted fragments; infra-isthmus fracture; angular malreduction; unsatisfactory reduction (fracture gap >5 mm); and treatment with single construct.

Patients over the age of 20 with concomitant ipsilateral femoral neck and shaft fractures diagnosed at a level one medical center between 2003 and 2019 were included. Treatment modalities included single construct with/without an antirotational screw for the neck and dual constructs. Radiographic outcomes were assessed from anteroposterior and lateral hip radiographs at follow-up. Fisher exact test was used to analyze categorical variables. The presence of avascular necrosis of the femoral head, delayed union, atrophic or hypertrophic nonunion of the femoral shaft fracture, and loss of reduction were identified as factors related to treatment failure.

A total of 22 patients were included in this study. The average age was 58.5 years, and the majority was male (68.2%). The minimum radiographic follow-up duration was 12 months, and the median follow-up time was 12 (interquartile range 12–24) months.

Femoral neck osteosynthesis failed in 3 patients, whereas femoral shaft osteosynthesis failed in 12 patients. Fisher exact test demonstrated the failure of femoral shaft osteosynthesis was significantly more frequent in the single-construct cohort in 16 infra-isthmus femoral fracture cases (P = .034).

In ipsilateral femoral neck and infra-isthmus shaft fractures, it is better to treat the neck and shaft fractures with separate implants (dual constructs).

In a dual-construct cohort, separate plate fixation of the femoral shaft achieved a better result in terms of bone union than retrograde nailing of the shaft (bone union rate: 4/8 vs 0/2).
Stereo-EEG Evaluation and Surgical Treatment in Patients With Drug-Resistant Focal Epilepsy Associated With Nodular Heterotopia
Authors: Durica Sarah R. , Caruso James P. , Podkorytova Irina , Ding Kan , Hays Ryan , Lega Bradley , Perven Ghazala
Published: April 2021

Purpose:

Nodular heterotopia (NH) is a common cause of drug-resistant epilepsy. Only limited studies detail the treatment of NH with laser interstitial thermal therapy and none analyze the relation between epileptogenicity and NH location.

Methods:

We retrospectively studied nine patients with drug-resistant epilepsy and NH who underwent stereoelectroencephalography and subsequent epilepsy surgery. Nodular heterotopia in the frontal lobes or along the bodies of the lateral ventricles was classified as anterior NH. Nodular heterotopia in the trigones, temporal or occipital horns, or temporal lobes was classified as posterior NH. Nodular heterotopia in both anterior and posterior locations was classified as diffuse NH. Interictal and ictal stereoelectroencephalography were analyzed, and patients were followed postoperatively to assess outcomes.

Results:

Of the six patients who underwent nine laser interstitial thermal therapy procedures either in isolation or in combination with other surgical therapies, four patients were Engel Ia, one was Engel IIb, and one was Engel IIIa, with an average follow-up of 22.8 months. All patients with posterior NH had interictal epileptiform abnormalities and seizures originating from the posterior NH. None of the patients with anterior NH had epileptiform activity recorded from their NH.

Conclusion:

Laser interstitial thermal therapy alone or in combination with other surgical therapies is an effective treatment in those with drug-resistant epilepsy because of NH, even in those with extensive NH and broad seizure onset. We observed a trend suggesting that posterior NH are more likely to be epileptogenic compared with anterior NH and recommend that in patients with anterior NH, alternative epilepsy etiologies and stereoelectroencephalography implantation strategies be considered.
Metabolic buffer analysis reveals the simultaneous, independent control of ATP and adenylate energy ratios
Authors: Hancock Edward J. , Krycer James R. , Ang Jordan
Published: April 2021

Determining the underlying principles behind biological regulation is important for understanding the principles of life, treating complex diseases and creating de novo synthetic biology. Buffering—the use of reservoirs of molecules to maintain molecular concentrations—is a widespread and important mechanism for biological regulation. However, a lack of theory has limited our understanding of its roles and quantified effects. Here, we study buffering in energy metabolism using control theory and novel buffer analysis. We find that buffering can enable the simultaneous, independent control of multiple coupled outputs. In metabolism, adenylate kinase and AMP deaminase enable simultaneous control of ATP and adenylate energy ratios, while feedback on metabolic pathways is fundamentally limited to controlling one of these outputs. We also quantify the regulatory effects of the phosphagen system—the above buffers and creatine kinase—revealing which mechanisms regulate which outputs. The results are supported by human muscle and mouse adipocyte data. Together, these results illustrate the synergy of feedback and buffering in molecular biology to simultaneously control multiple outputs.
Turing instability in an economic–demographic dynamical system may lead to pattern formation on a geographical scale
Authors: Zincenko Anna , Petrovskii Sergei , Volpert Vitaly , Banerjee Malay
Published: April 2021

Spatial distribution of the human population is distinctly heterogeneous, e.g. showing significant difference in the population density between urban and rural areas. In the historical perspective, i.e. on the timescale of centuries, the emergence of densely populated areas at their present locations is widely believed to be linked to more favourable environmental and climatic conditions. In this paper, we challenge this point of view. We first identify a few areas at different parts of the world where the environmental conditions (quantified by the temperature, precipitation and elevation) show a relatively small variation in space on the scale of thousands of kilometres. We then examine the population distribution across those areas to show that, in spite of the approximate homogeneity of the environment, it exhibits a significant variation revealing a nearly periodic spatial pattern. Based on this apparent disagreement, we hypothesize that there may exist an inherent mechanism that may lead to pattern formation even in a uniform environment. We consider a mathematical model of the coupled demographic-economic dynamics and show that its spatially uniform, locally stable steady state can give rise to a periodic spatial pattern due to the Turing instability, the spatial scale of the emerging pattern being consistent with observations. Using numerical simulations, we show that, interestingly, the emergence of the Turing patterns may eventually lead to the system collapse.
Modelling the impact of household size distribution on the transmission dynamics of COVID-19
Authors: Liu Pengyu , McQuarrie Lisa , Song Yexuan , Colijn Caroline
Published: April 2021

Under the implementation of non-pharmaceutical interventions such as social distancing and lockdowns, household transmission has been shown to be significant for COVID-19, posing challenges for reducing incidence in settings where people are asked to self-isolate at home and to spend increasing amounts of time at home due to distancing measures. Accordingly, characteristics of households in a region have been shown to relate to transmission heterogeneity of the virus. We introduce a discrete-time stochastic epidemiological model to examine the impact of the household size distribution in a region on the transmission dynamics. We choose parameters to reflect incidence in two health regions of the Greater Vancouver area in British Columbia and simulate the impact of distancing measures on transmission, with household size distribution the only different parameter between simulations for the two regions. Our result suggests that the dissimilarity in household size distribution alone can cause significant differences in incidence of the two regions, and the distributions drive distinct dynamics that match reported cases. Furthermore, our model suggests that offering individuals a place to isolate outside their household can speed the decline in cases, and does so more effectively where there are more larger households.
Challenges in forming inferences from limited data: a case study of malaria parasite maturation
Authors: Peters Madeline A. E. , Greischar Megan A. , Mideo Nicole
Published: April 2021

Inferring biological processes from population dynamics is a common challenge in ecology, particularly when faced with incomplete data. This challenge extends to inferring parasite traits from within-host infection dynamics. We focus on rodent malaria infections (Plasmodium berghei), a system for which previous work inferred an immune-mediated extension in the length of the parasite development cycle within red blood cells. By developing a system of delay-differential equations to describe within-host infection dynamics and simulating data, we demonstrate the potential to obtain biased estimates of parasite (and host) traits when key biological processes are not considered. Despite generating infection dynamics using a fixed parasite developmental cycle length, we find that known sources of measurement bias in parasite stage and abundance data can affect estimates of parasite developmental duration, with stage misclassification driving inferences about extended cycle length. We discuss alternative protocols and statistical methods that can mitigate such misestimation.
Quantifying biologically essential aspects of environmental light
Authors: Nilsson Dan-E. , Smolka Jochen
Published: April 2021

Quantifying and comparing light environments are crucial for interior lighting, architecture and visual ergonomics. Yet, current methods only catch a small subset of the parameters that constitute a light environment, and rarely account for the light that reaches the eye. Here, we describe a new method, the environmental light field (ELF) method, which quantifies all essential features that characterize a light environment, including important aspects that have previously been overlooked. The ELF method uses a calibrated digital image sensor with wide-angle optics to record the radiances that would reach the eyes of people in the environment. As a function of elevation angle, it quantifies the absolute photon flux, its spectral composition in red–green–blue resolution as well as its variation (contrast-span). Together these values provide a complete description of the factors that characterize a light environment. The ELF method thus offers a powerful and convenient tool for the assessment and comparison of light environments. We also present a graphic standard for easy comparison of light environments, and show that different natural and artificial environments have characteristic distributions of light.
Probability distributions of helminth parasite burdens within the human host population following repeated rounds of mass drug administration and their impact on the transmission breakpoint
Authors: Collyer Benjamin S. , Anderson Roy M.
Published: April 2021

The existence of multiple stable equilibria in models of parasitic helminth transmission was a ground-breaking discovery over 30 years ago. An implication of this discovery, that there is a level of infection below which transmission cannot self-sustain called the transmission breakpoint, has in part motivated the push towards the elimination of many human diseases caused by the multiple species of helminth worldwide. In the absence of vaccines, the predominant method in this push towards elimination is to repeatedly administer endemic populations with anthelmintic drugs, over several treatment rounds, in what has become to be known as mass drug administration (MDA). MDA will inevitably alter the distribution of parasite burdens among hosts from the baseline distribution, and significantly, the location of the transmission breakpoint is known to be dependent on the level of aggregation of this distribution—for a given mean worm burden, more highly aggregated distributions where fewer individuals harbour most of the burden, will have a lower transmission breakpoint. In this paper, we employ a probabilistic analysis of the changes to the distribution of burdens in a population undergoing MDA, and simple approximations, to determine how key aspects of the programmes (including compliance, drug efficacy and treatment coverage) affect the location of the transmission breakpoint. We find that individual compliance to treatment, which determines the number of times an individual participates in mass drug administration programmes, is key to the location of the breakpoint, indicating the vital importance to ensure that people are not routinely missed in these programmes.
Interleukin-6 receptor genetic variation and tocilizumab treatment response to COVID-19
Authors: Almarzooq Ammar Ali
Published: April 2021

Interleukin-6 receptor (IL6R) stimulates the inflammatory pathways as part of the acute-phase response to infection. Tocilizumab is a monoclonal antibody that inhibits both membrane-bound and soluble IL6R and is used to treat inflammatory conditions, including COVID-19. Despite the disproportionate incidence of COVID-19 among underserved, racial, and ethnic minority populations, the efficacy of tocilizumab in hospitalized COVID-19 patients from these populations is unclear. In this work, three genetic markers for the IL6R gene were analyzed across diverse ethnic backgrounds to identify population differences in response to tocilizumab treatment. Genetic structure analyses showed that African populations were significantly different from other described populations. In addition, mapped frequencies of these alleles showed that Sub-Saharan African populations were 3.4x more likely to show an impaired response to tocilizumab than East Asian populations, and 1.8x more likely than European ancestry populations. Existing IL6R genotype results may identify populations at increased therapeutic failure risk. As results from current clinical trials on the efficacy of tocilizumab treatment for extreme COVID-19 infections are conflicting, more studies are needed across diverse patient backgrounds to better understand the genetic factors necessary to predict treatment efficacy. This work demonstrates how pharmacogenomics studies can elucidate genetic variation on treatment efficacy on COVID-19.
Trends of SARS-CoV-2 antibody prevalence in selected regions across Ghana
Authors: Quashie Peter Kojo , Mutungi Joe Kimanthi , Dzabeng Francis , Oduro-Mensah Daniel , Opurum Precious C. , Tapela Kesego , Udoakang Aniefiok John ,   WACCBIP COVID-19 Team, Asante Ivy , Paemka Lily , Kumi-Ansah Frederick , Quaye Osbourne , Amoako Emmanuella , Armah Ralph , Kilba Charlyne , Boateng Nana Afia , Ofori Michael , Kyei George B. , Bediako Yaw , Ndam Nicaise , Abugri James , Ansah Patrick , Ampofo William K. , Mutapi Francisca , Awandare Gordon A.
Published: April 2021

To estimate the level of community exposure to SARS-CoV-2 in Ghana, we conducted phased seroprevalence studies of 2729 participants in selected locations across Ghana. Phase I screening (August 2020) covered a total of 1305 individuals screened at major markets/lorry stations, major shopping malls, hospitals and research institutions involved in COVID-19 work. The screening was performed using a strip-in-cassette lateral flow type Rapid Diagnostic Test (RDT) kit that simultaneously and separately detected IgM and IgG antibodies against SARS-CoV-2 nucleocapsid protein. In Phase I, 252/1305 (19%) tested positive for IgM or IgG or both. Exposure rate was significantly higher among individuals tested at markets/lorry stations (26.9%) compared to those at Shopping Malls (9.4%). The 41–60-years age group had the highest exposure rate (27.2%). People with only a basic level or no formal education had a higher exposure rate (26.2%) than those with tertiary level education (13.1%); and higher in informally employed workers (24.0%) than those in the formal sector (15.0%). Phases II and III screening activities in October and December 2020, respectively, showed no evidence of increased seroprevalence, indicating either a reduced transmission rate or loss of antibody expression in a subset of the participants. The Upper East region has the lowest exposure rate, with only 4 of 200 participants (2%) seropositivity. Phase IV screening in February 2021 showed that exposure rates in the upper income earners (26.2%) had almost doubled since August 2020, reflective of Ghana’s second wave of symptomatic COVID-19 cases, which began in December 2020. The Phase IV results suggest that seroprevalence levels have become so high that the initial socioeconomic stratification of exposure has been lost. Overall, the data indicates a much higher COVID-19 seroprevalence in the Greater Accra Region than was officially acknowledged, likely implying a considerably lower case fatality rate than the current national figure of 0.84%. Additionally, the high exposure levels seen in the communities suggest that COVID-19 in Ghana still predominantly presents with none-to-mild symptoms. Our results lay the foundation for more extensive SARS-CoV-2 surveillance in Ghana and the West African sub-region, including deploying rapid antigen test kits in concert to determine the actual infection burden since antibody development lags infection.
Forecasting COVID-19 disease cases using the SARIMA-NNAR hybrid model
Authors: Demir İbrahim , Kirişci Murat
Published: April 2021

Background

COVID-19 is a new disease that is associated with high morbidity that has spread around the world. Credible estimating is crucial for control and prevention. Nowadays, hybrid models have become popular, and these models have been widely implemented. Better estimation accuracy may be attained using time-series models. Thus, our aim is to forecast the number of COVID-19 cases with time-series models.

Objective

Using time-series models to predict deaths due to COVID-19.

Design

SARIMA, NNAR, and SARIMA-NNAR hybrid time series models were used using the COVID-19 information of the Republic of Turkey Health Ministry.

Participants

We analyzed data on COVID-19 in Turkey from March 11, 2020 to February 22, 2021.

Main Measures

Daily numbers of COVID-19 confirmed cases and deaths.

Materials and methods

We fitted a seasonal autoregressive integrated moving average (SARIMA)–neural network nonlinear autoregressive (NNAR) hybrid model with COVID-19 monthly cases from March 11, 2020, to February 22, 2021, in Turkey. Additionally, a SARIMA model, an NNAR model, and a SARIMA–NNAR hybrid model were established for comparison and estimation.

Results

The RMSE, MAE, and MAPE values of the NNAR model were obtained the lowest in the training set and the validation set. Thus, the NNAR model demonstrates excellent performance whether in fitting or forecasting compared with other models.

Conclusions

The NNAR model that fits this study is the most suitable for estimating the number of deaths due to COVID-19. Hence, it will facilitate the prevention and control of COVID-19.
Atypical Resting State Functional Connectivity in Mild Traumatic Brain Injury
Authors: Amir Joelle , Raghavan Nair Jay Kumar , Del Carpio Raquel , Ptito Alain , Chen Jen-Kai , Chankowsky Jeffrey , Tinawi Simon , Lunkova Ekaterina , Saluja Rajeet Singh
Published: April 2021

Objectives

This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode (DMN), salience (SN), and task-positive networks (TPN)) in individuals who had sustained a mild traumatic brain injury (mTBI).

Methods

Resting-state functional magnetic resonance imaging (rs-fMRI) data was acquired from 27 mTBI patients with persistent post-concussive symptoms (PCS), along with 26 age- and sex-matched controls. These individuals were recruited from a Level-1 trauma centre, at least three months after a traumatic episode. IFCNs were established based on seed-to-voxel, region-of-interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and PCS.

Results

Seed-to-voxel analysis of rs-fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo- and hyperconnectivity, dependent on seed location. Within network hypoconnectivity was observed in the visual network, also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioural symptoms score was also found.

Conclusions

Our findings indicate that rs-fMRI may be of use clinically, in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent post-concussive symptoms months after injury, who hope to resume activity.
Modeling microbial diversity across different soil ecosystems and environmental covariate selections in tropical SE Asian landscape
Authors: Wibowo Andri
Published: April 2021

Microbes play essential roles in the ecology of various environments and structure. Diversity of soil microbial communities is an important scientific interest in tropical landscape including in South East Asia. Soil environment in SE Asia is diverse and this influences the microbial diversity. Soil microbes in this study were collected using DNA isolation protocols and the whole microbial community structure of sampled soil was analyzed through next generation sequencing. Soil microbial identification was conducted by amplifying the 16S rRNA gene. Soils were sampled from 4 different environments in Sumatra and Kalimantan ecosystems representing plantation, swamp, peatland, and coastal ecosystems. Measured soil covariates including soil organic carbon C analyzed based on the Walkley-Black method and Kjeldahl method for N. Model of microbes in soil ecosystems were based on Akaike model selection (AIC) by testing the influence of soil covariates on soil microbial phylum. The microbial community was found to be comprising of a total number of 11 phyla. In soil of coastal ecosystem, microbial diversity at phylum level were dominated by Proteobacteria (82.3%), Actinobacteria (9.41%), Acidobacteria (4.7%), and the lowest was Bacteroidetes and Chloroflexi (0.58%). In plantation soil, the microbial abundance order was Firmicutes (41.6%) > Actinobacteria (29.7%) > Acidobacteria (20.0%) > Gemmatimonadetes (5.94%). The soil microbial abundance order in swamp was Proteobacteria (42.2%) > Acidobacteria (20.04%) > Bacteroidetes > (10.46%) > Actinobacteria (9.24%). In soil of peatland ecosystem, taxonomic assignments of microbial at the phylum level were dominated by Firmicutes (66.18%), Proteobacteria(16.94%), and Actinobacteria (16.87%). According to the values of AIC, Firmicutes was a microbial phylum that has high abundance in soil ecosystems influenced by pH covariates with AIC values of −6.54. Other soil covariates show less influence on Firmicutes with AIC values of −5.06. The combination model also show that pH cofactor was the important determinants with AIC values of −0.54 for Firmicutes (pH+C) and Firmicutes (pH+N) models. While AIC value for combination model of Firmicutes (C+N) only equals to 0.14.
Role of Ori inThermococcus barophilus
Authors: Moalic Yann , Catchpole Ryan , Leroy Elodie , Teer Logan Mc , Cueff-Gauchard Valérie , Aubé Johanne , Lu Yang , Roussel Erwan , Oberto Jacques , Flament Didier , Dulermo Rémi
Published: April 2021

The mechanisms underpinning replication of genomic DNA in Archaea have recently been challenged. Species belonging to two different taxonomic orders grow well in the absence of an origin of replication, challenging the role of the replication origin in these organisms. Here, we pursue the investigation of the particular way some archaea manage their DNA replication withThermococcus barophilusand the role of Ori in this Archaea. Surprisingly we discovered thatT. barophilususes its Ori all along the growth curve with marked increase at the end of exponential phase. Through gene deletion, we show that Ori utilization requires Cdc6, and that origin deletion results in increased time in lag phase and a moderate decrease of growth rate in mutants. The number of chromosomes are quite similar between both strains during exponential and early stationary phases but differs after 24h of growth where ΔTbOriC has only 6 chromosomes/cell compared to 10 for the reference strain (WT). Following 1hr of growth in fresh media, ΔTbOriC strains contains 3 chromosome copies/cell, whereas the WT contains only 1. We hypothesize that theT. barophilusmight degrade DNA to obtain energy to start replication and cell division, whereas the ΔTbOriC must maintain more chromosomal copies in order to initiate DNA replication in the absence of an origin or replication. Finally, we analyzed the role of Ori at temperatures above or below the optimal temperature, revealing that Ori is important to start growth at those temperatures, suggesting that replication origins may be involved in stress response.
ElectroEncephaloGraphy robust statistical linear modelling using a single weight per trial
Authors: Pernet Cyril , Rousselet Guillaume , Mas Ignacio Suay , Martinez Ramon , Wilcox Rand , Delorme Arnaud
Published: April 2021

Being able to remove or weigh down the influence of outlier data is desirable for any statistical models. While Magnetic and ElectroEncephaloGraphic (MEEG) data are often averaged across trials per condition, it is becoming common practice to use information from all trials to build statistical linear models. Individual trials can, however, have considerable weight and thus bias inferential results (effect sizes as well as thresholded t/F/p maps). Here, rather than looking for univariate outliers, defined independently at each measurement point, we apply the principal component projection (PCP) method at each channel, deriving a single weight per trial at each channel independently. Using both synthetic data and open EEG data, we show (1) that PCP is efficient at detecting a large variety of outlying trials; (2) how PCP-based weights can be implemented in the context of the general linear model (GLM) with accurate control of type 1 family-wise error rate; and (3) that our PCP-based Weighted Least Square (WLS) approach increases the statistical power of group analyses as well as a much slower Iterative Reweighted Least Squares (IRLS), although the weighting scheme is markedly different. Together, our results show that WLS based on PCP weights derived from whole trial profiles is an efficient method to weigh down the influence of outlier EEG data in linear models.

Data availability

all data used are publicly available (CC0), all code (simulations and data analyzes) is also available online in the LIMO MEEG GitHub repository (MIT license).