bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Walking Speed to Achieve a Pre-training Endurance Shuttle Walk Time of 5-10 min May Improve Test Responsiveness in People With Chronic Obstructive Pulmonary Disease
Authors: Hill Kylie , Chao Yan Ling , Cavalheri Vinicius , Ng L. W. Cindy , Wootton Sally L. , McKeough Zoe J. , Jenkins Sue C. , Eastwood Peter R. , Hillman David R. , Jenkins Christine , Cecins Nola , Spencer Lissa M. , Alison Jennifer A.
Published: April 2021

Purpose:

The endurance shuttle walk test (ESWT) was used to evaluate ground-based walking training in chronic obstructive pulmonary disease. During pre-training testing, those who walked 5-10 min on the first ESWT with minimal symptoms performed additional ESWTs at increasing speeds until they were at least moderately symptomatic and terminated the test between 5 and 10 min. This report compares participant characteristics and test responsiveness with participants grouped according to whether or not faster walking speeds were selected for the ESWT during pre-training testing.

Methods:

We conducted a retrospective analysis of data collected in the intervention group during a randomized controlled trial. The intervention was supervised ground-based walking training, performed two to three times/wk, for 8-10 wk. Prior to and immediately following completion of training, participants completed the 6-min walk test (6MWT), incremental shuttle walk test (ISWT), and ESWT.

Results:

Data were available on 77 participants (70 ± 9 yr, forced expiratory volume in the first second of expiration [FEV1] 43 ± 15 % predicted). For those whom a faster speed was selected during the pre-training ESWTs were characterized by milder dyspnea and leg fatigue on completion of the baseline 6MWT and ISWT (P < .05 for all). On training completion, the change in ESWT was greater in those for whom a faster speed was selected (376 ± 344 sec vs 176 ± 274 sec; P = .017).

Conclusions:

Participants who report modest symptoms on completion of the pre-training 6MWT or ISWT may achieve a long pre-training ESWT time. In this situation, repeating the pre-training ESWT at a faster walking speed to achieve an exercise time between 5 and 10 min with moderate symptoms may be advantageous.
Protective strategy of parathyroid glands during thyroid lobectomy
Authors: Xing Zhichao , Qiu Yuxuan , Fei Yuan , Xia Baoying , Abuduwaili Munire , Zhu Jingqiang , Su Anping
Published: April 2021

Parathyroid protection during thyroid lobectomy was not illustrated previously. Aim of this study was to find out the influence of parathyroid glands in situ preservation and autotransplantation on postoperative parathyroid function in thyroid lobectomy.

Consecutive patients who underwent primary thyroid lobectomy with unilateral central neck dissection for papillary thyroid carcinoma in our center were included retrospectively. Postoperative hypoparathyroidism was defined as low parathyroid hormone (PTH) levels (<1.6 pmol/L) and keeping over 6 months was defined as permanent. Patients were divided into 3 groups: all identified parathyroid glands preserved in situ (preservation group); at least one parathyroid gland autotransplanted without accidental resection (autotransplantation group); at least one parathyroid gland accidental resected (resection group).

A total of 425 patients were included. No permanent hypoparathyroidism was reported, and the rates of transient hypoparathyroidism were similar among all groups. Significantly lower serum PTH levels were found in autotransplantation group versus preservation group at postoperative 1-day (3.77 ± 1.61 vs 4.72 ± 2.31, P < .001). Transient hypoparathyroidism was significantly associated with reduced intraoperative carbon nanoparticles utilization (57.1% vs 77.4%, P = .039).

Thyroid lobectomy was a safe surgical method for parathyroid protection no matter the practice to ipsilateral parathyroid glands. However, preservation of all parathyroid glands was still recommended considering relatively stable PTH levels.
The effect of insulin pump combined with ulinastatin on the levels of PCT, TG, PTX-3, and CX3CL1 in patients with diabetic ketoacidosis and pancreatitis
Authors: Wei Dongmei , Yin Chao , Lu Songtao , Xiong Juwen , Zhu Lishuang , Yan Shaoru , Meng Rui
Published: April 2021

The aim of this research is to observe the effect of insulin pump combined with Ulinastatin on the levels of procalcitonin (PCT), triglycerides (TG), pentraxin-3(PTX-3), and C-X3-C motif chemokine ligand 1 (CX3CL1) in patients with diabetic ketoacidosis and pancreatitis.

A total of 72 patients with diabetic ketoacidosis and pancreatitis who were admitted to our hospital from February 2016 to February 2020 were selected as the research subjects. They were divided into study groups (36 cases, given insulin pump combined Ulinastatin treatment) and control group (36 cases, given insulin pump treatment). Statistics of changes in blood amylase (AMS), blood glucose, blood ketones, glycosylated hemoglobin (HbA1c), PCT, TG, PTX-3, and chemokine CX3CL in pancreatic tissue before and after treatment.

After treatment, the clinical efficacy of the study group was significantly higher than that of the control group (94.44% vs 75.00%), the difference was significant (P < .05). After treatment, the clinical symptoms (abdominal distension, abdominal pain, body temperature, blood sugar, HbA1c and blood amylase) in the study group were significantly less time-to-normal than in the control group, and the difference was significant (P < .05). After treatment, the AMS, blood sugar, HbA1c, and blood ketones of the 2 groups were all lower than before treatment, and the study group's AMS, blood sugar, HbA1c, and blood ketones were all lower In the control group, the difference was significant (P < .05). After treatment, the 2 groups of PCT, TG, PTX-3, and CX3CL were all lower than before treatment, among which the study group PCT, TG, PTX-3, and CX3CL1 were lower than the control group, the difference was significant (P < .05). After treatment, the total adverse reaction rate of the 2 groups was not significantly different (P > .05), but the total adverse reaction rate of the study group was lower than that of the control group.

The combination of insulin pump and ulinastatin in the treatment of patients with diabetic ketoacidosis complicated with acute pancreatitis has a effect, which can shorten the recovery time of clinical symptoms, reduce the levels of PCT, TG, PTX-3, and CX3CL1, and has fewer adverse reactions. It is worthy of clinical application.
MicroRNA-496 inhibits triple negative breast cancer cell proliferation by targeting Del-1
Authors: Lee Soo Jung , Jeong Jae-Hwan , Lee Jeeyeon , Park Ho Yong , Jung Jin Hyang , Kang Jieun , Kim Eun Ae , Park Nora Jee-Young , Park Ji-Young , Lee In Hee , Chae Yee Soo
Published: April 2021

Del-1 has been linked to the pathogenesis of various cancers, including breast cancer. However, the regulation of Del-1 expression remains unclear. We previously reported the interaction between microRNA-137 (miR-137) and the Del-1 gene. In this study, we investigated miR-496 and miR-137 as regulators of Del-1 expression in triple negative breast cancer (TNBC). Del-1 mRNA and miR-496 were measured by quantitative PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-496 on cell proliferation, migration, and invasion were determined with MTT, wound healing, and Matrigel transwell assays, respectively. In MDA-MB-231 cells, miR-496 levels were remarkably low and Del-1 mRNA levels were higher than in other breast cancer cell lines. Luciferase reporter assays revealed that miR-496 binds the 3′-UTR of Del-1 and Del-1 expression is downregulated by miR-496 mimics. Furthermore, miR-496 inhibited the proliferation, migration, and invasion of MDA-MB-231 cells. The effects of miR-496 on cell proliferation were additive with those of miR-137, another miRNA that regulates Del-1 expression. Moreover, in the 30 TNBC specimens, miR-496 was downregulated (P < .005) and the levels of Del-1 in the plasma were significantly elevated as compared with in normal controls (P = .0142). The Cancer Genome Atlas (TCGA) data showed the correlation of miR-496 expression with better overall survival in patients with early TNBC. In in silico and in vitro analyses, we showed that Del-1 is a target of miR-496 in TNBC and thereby affects cancer progression. Our findings suggest that miR-496 and miR-137 additively target Del-1 and act as modulating factors in TNBC. They are potentially new biomarkers for patients with TNBC.
Randomized clinical trial of preoperative skin preparation with 2% chlorhexidine versus conventional hair shaving in percutaneous coronary intervention
Authors: Tsai Hsueh-Ya , Liao Wen-Chun , Wang Meilin , Ueng Kwo-Chang , Huang Cheng-Yi , Tseng Ying-Chen
Published: April 2021

Background:

Preoperative skin preparation is associated with surgical site infection (SSI). Traditional preoperative shaving fails to reduce the risk of SSI. The efficacy of 2% chlorhexidine for preoperative skin preparation in percutaneous coronary intervention (PCI) is sketchy. The aim of this trial was to evaluate whether preoperative skin preparation performed with chlorhexidine was not inferior to a conventional hair removal method.

Methods:

Seventy-eight patients undergoing PCI were randomized into 2 groups of 39 patients, receiving either single sterilization with 2% chlorhexidine or hair shaving respectively between July 2016 and October 2016. The primary endpoints were wound infection rate and bacterial counts. Secondary endpoints were rate of SSI and adverse effects of 2% chlorhexidine.

Results:

The results showed that 2% chlorhexidine significantly reduced the colonization of Staphylococcus aureus (P = .032), S epidermidis (P = .000), and miscellaneous bacteria (P = .244) in comparison with hair shaving, respectively. Redness in 24 hours after surgery was observed in 6 patients in the control group (15.4%) and 5 patients (12.8%) in 2% chlorhexidine group. There was no statistically significant difference in SSI rate between 2 skin preparations.

Conclusion:

In PCI, preoperative skin preparation with 2% chlorhexidine was not inferior to conventional hair shaving in terms of the wound infection rate and SSI rate.
Ovarian dysgerminoma in pregnancy
Authors: Sas Ioan , Şerban Denis Mihai , Tomescu Larisa - Cristina , Nicolae Nicoleta
Published: April 2021

Rationale:

Although dysgerminomas are relatively uncommon among all ovarian neoplasms, representing for only about 2%, they account for 32.8 percent of malignant ovarian germ cell tumors. Their association with pregnancy is extremely rare; due to the low frequency of occurrence, there are few recommendations regarding pregnancy management; therefore, it is important to discuss and summarize the treatment strategy.

Patient concerns:

We present the case of a 25 years patient, gestation 1, para 1, who was hospitalized in the clinic at 38/39 weeks of gestation at the beginning of labor. Following the ultrasound examination, a hypoechogenic lesion on the uterine fundus was found, suggestive of subterranean fibroid. After caesarean section, right adnexectomy was performed; the histopathological examination revealed, unexpectedly, the diagnosis of dysgerminoma.

Diagnoses:

Dysgerminoma as associated with pregnancy.

Interventions:

Birth by Caesarean section and right adnexectomy. No other medical complications occurred.

Outcomes:

The histopathological and immunohistochemical examinations were consistent with the pure dysgerminoma. Oncology was staged AI, with the monitoring of markers and abdominal and pelvic magnetic resonance imaging at 3, 6, 9, and 12 months.

Lessons:

Dysgerminoma is the most common ovarian malignancy associated with pregnancy with a good fetal maternal outcome. If these tumors are discovered accidentally during caesarean section, tumor markers and magnetic resonance imaging scanning should be done postoperatively to plan optimal treatment.
Posterior Reversible Encephalopathy Syndrome: Incidence and Clinical Characteristics in Children With Cancer
Authors: Sommers Katherine R. , Skiles Jodi , Leland Brian , Rowan Courtney M.
Published: April 2021

The etiology and outcomes of posterior reversible encephalopathy syndrome (PRES) in children with cancer are not well understood. We aim to determine the incidence of PRES, describe associated morbidity and mortality, and better understand risk factors in this patient population. A total of 473 children with a hematologic malignancy or postallogeneic hematopoietic cell transplantation between June 2015 and June 2020 were screened for PRES to determine incidence and whether age or underlying diagnosis are associated with development of PRES. We conducted a case-control study to evaluate whether comorbidities or chemotherapeutic agents are associated with PRES. Children with PRES were matched with 2 controls based on age and underlying diagnosis to identify additional risk factors. Fourteen patients developed PRES, with an incidence of 5.9/1000 people/year. Those diagnosed with PRES had commonly described PRES symptoms: hypertension, seizures, nausea/vomiting, altered mental status, and headaches. All patients received an magnetic resonance imaging, and most had findings consistent with PRES. Hematopoietic cell transplantation was associated with the development of PRES. The use of Etoposide was associated with PRES but comorbidities, steroids and calcineurin inhibitors were not. While PRES was infrequent in this population, it is associated with high morbidity and mortality, with ICU admissions and an overall hospital mortality, because of secondary causes, of 29%.
Roseola Infantum During the COVID-19 Pandemic
Authors: Aktürk Hacer , Bağci Mihrimah S. , Yiğit Murat H. , Khalilova Fidan , Ünlügedik Özlem , Asarcikli Fikret
Published: April 2021

Introduction:

Roseola infantum is always considered to be among the differential diagnosis of young patients with fever and leukopenia whom to be strictly isolated with the preliminary diagnosis of COVID-19 until otherwise proven during the pandemic.

Results:

Human herpes virus-6 (HHV-6) polymerase chain reaction (PCR) blood test was performed in 4 of 7 patients with a clinical diagnosis of roseola infantum and all found to be HHV-6 PCR positive. The most striking laboratory finding in all patients was leukopenia. HHV-6 PCR tests were found to be positive. Severe acute respiratory syndrome coronavirus-2 testing were found to be negative in all patients.

Conclusion:

During the peak of the pandemic, children continued to present with fever because of viral infections other than COVID-19.
Analysis of the Peripapillary Choroidal Vascular Characteristics in Papilledema Associated with Pseudotumor Cerebri
Authors: Kesim Cem , Solmaz Banu , Pasaoglu Isil , Karslioglu Melisa Zisan , Tatar Ipek , Yildiz-Tas Ayse , Zabun Burak , Sahin Afsun , Gedik Sansal
Published: April 2021

SIGNIFICANCE

Choroidal vascularity index measured by image binarization method from peripapillary optical coherence tomography sections has been found significantly lower in papilledema patients than healthy controls.

PURPOSE

The purpose of this study was to compare peripapillary choroidal parameters in papilledema patients with control subjects.

METHODS

Peripapillary spectral domain optical coherence tomography scans of 34 patients with papilledema and 34 healthy controls are acquired for the study. Images are binarized with the ImageJ software (National Institutes of Health, Bethesda, MD) to calculate total choroidal area, stromal area, luminal area, and choroidal vascularity index.

RESULTS

Total choroidal area, luminal area, and choroidal vascularity were significantly lower in papilledema patients compared with healthy controls on right (1.343 ± 0.286 vs. 1.694 ± 0.344, P < .001; 0.880 ± 0.209 vs. 1.167 ± 0.255, P < .001; 65.28 ± 2.99% vs. 68.68 ± 2.81%, P < .001, respectively) and left eyes (1.376 ± 0.308 vs. 1.647 ± 0.339, P < .001; 0.899 ± 0.231 vs. 1.134 ± 0.237, P < .001; 64.92 ± 3.44 vs. 68.84 ± 3.23, P < .001, respectively). No difference was found between active and remitted stages of papilledema in terms of choroidal parameters.

CONCLUSIONS

Peripapillary total choroidal area, luminal area, and choroidal vascularity index are significantly reduced in patients with papilledema. These parameters might be beneficial tools for evaluating choroidal vascularity in papilledema quantitatively and differential diagnosis for optic disc edema.
Morphology Matters
Authors: Jesinghaus Moritz , Schmitt Maxime , Lang Corinna , Reiser Marianne , Scheiter Alexander , Konukiewitz Björn , Steiger Katja , Silva Miguel , Tschurtschenthaler Markus , Lange Sebastian , Foersch Sebastian , Becker Karl F. , Saur Dieter , Friess Helmut , Halfter Kathrin , Engel Jutta , Boxberg Melanie , Pfarr Nicole , Wilhelm Dirk , Weichert Wilko
Published: April 2021

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding—but not WHO grade—being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.
Significance of Alpha-inhibin Expression in Pheochromocytomas and Paragangliomas
Authors: Mete Ozgur , Pakbaz Sara , Lerario Antonio M. , Giordano Thomas J. , Asa Sylvia L.
Published: April 2021

Alpha-inhibin expression has been reported in pheochromocytomas and paragangliomas (PPGLs). We analyzed alpha-inhibin immunohistochemistry in 77 PPGLs (37 pheochromocytomas [PCCs] and 40 paragangliomas) and correlated the results with catecholamine profile, tumor size, Ki-67 labeling index, succinate dehydrogenase B subunit and carbonic anhydrase IX (CAIX) staining, and genetic pathogenesis. PPGLs were classified as pseudohypoxic cluster 1 disease with documented VHL mutation or SDHx mutation or biochemical phenotype, whereas NF1-driven and RET-driven PPGLs and those with a mature secretory (adrenergic or mixed adrenergic and noradrenergic) phenotype were classified as cluster 2 disease. The Cancer Genome Atlas data on INHA expression in PPGLs was examined. Alpha-inhibin was positive in 43 PPGLs (56%). Ki-67 labeling indices were 8.07% and 4.43% in inhibin-positive and inhibin-negative PPGLs, respectively (P<0.05). Alpha-inhibin expression did not correlate with tumor size. Alpha-inhibin was expressed in 92% of SDHx-related and 86% of VHL-related PPGLs. CAIX membranous staining was found in 8 of 51 (16%) tumors, including 1 SDHx-related PCC and all 5 VHL-related PCCs. NF1-driven and RET-driven PPGLs were negative for alpha-inhibin and CAIX. Alpha-inhibin was expressed in 77% of PPGLs with a pseudohypoxia signature, and 20% of PPGLs without a pseudohypoxia signature (P<0.05). PPGLs with a mature secretory phenotype were negative for CAIX. The Cancer Genome Atlas data confirmed higher expression of INHA in cluster 1 than in cluster 2 PPGLs. This study identifies alpha-inhibin as a highly sensitive (90.3%) marker for SDHx/VHL-driven pseudohypoxic PPGLs. Although CAIX has low sensitivity, it is the most specific biomarker of VHL-related pathogenesis. While alpha-inhibin cannot replace succinate dehydrogenase B subunit immunohistochemistry for detection of SDHx-related disease, it adds value in prediction of cluster 1 disease. Importantly, these data emphasize that alpha-inhibin is not a specific marker of adrenal cortical differentiation, as it is also expressed in PCCs.
MRI Dynamic Contrast Imaging of Oral Cavity and Oropharyngeal Tumors
Authors: Sideras Panagiotis , Singh Gagandeep
Published: April 2021

In the past decade, dynamic contrast-enhanced magnetic resonance imaging has had an increasing role in assessing the microvascular characteristics of various tumors, including head and neck cancer. Dynamic contrast-enhanced magnetic resonance imaging allows noninvasive assessment of permeability and blood flow, both important parametric features of tumor hypoxia, which is in turn a marker for treatment resistance for head and neck cancer.

In this article we will provide a comprehensive review technique in evaluating tumor proliferation and application of its parameters in differentiating between various tumor types of the oral cavity and how its parameters can correlate between epidermal growth factor receptor and human papillomavirus which can have an implication in patient's overall survival rates.

We will also review how the parameters of this method can predict local tumor control after treatment and compare its efficacy with other imaging modalities. Lastly, we will review how its parameters can be used prospectively to identify early complications from treatment.
Quantification of Vibrio cholerae cholix exotoxin by sandwich bead-ELISA
Authors: Awasthi Sharda Prasad , Chowdhury Nityananda , Hatanaka Noritoshi , Hinenoya Atsushi , Ramamurthy Thandavarayan , Asakura Masahiro , Yamasaki Shinji
Published: April 2021

Introduction. Cholix toxin (ChxA) is an ADP-ribosylating exotoxin produced by

Vibrio cholerae

. However, to date, there is no quantitative assay available for ChxA, which makes it difficult to detect and estimate the level of ChxA produced by

V. cholerae

.

Hypothesis/Gap Statement. It is important to develop a reliable and specific quantitative assay to measure the production level of ChxA, which will help us to understand the role of ChxA in

V. cholerae

pathogenesis.

Aim. The aim of this study was to develop a bead-based sandwich ELISA (bead-ELISA) for the quantification of ChxA and to evaluate the importance of ChxA in the pathogenesis of

V. cholerae

infection.

Methodology. Anti-rChxA was raised in New Zealand white rabbits, and Fab-horse radish peroxidase conjugate was prepared by the maleimide method to use in the bead-ELISA. This anti-ChxA bead-ELISA was applied to quantify the ChxA produced by various

V. cholerae

strains. The production of ChxA was examined in different growth media such as alkaline peptone water (APW), Luria-Bertani broth and AKI. Finally, the assay was evaluated using a mouse lethality assay with representative

V. cholerae

strains categorized as low to high ChxA-producers based on anti-ChxA bead-ELISA.

Results. A sensitive bead-ELISA assay, which can quantify from 0.6 to 60 ng ml−1 of ChxA, was developed. ChxA was mostly detected in the extracellular cell-free supernatant and its production level varied from 1.2 ng ml−1 to 1.6 µg ml−1. The highest ChxA production was observed when

V. cholerae

strains were cultured in LB broth, but not in APW or AKI medium. The ChxA-producer

V. cholerae

strains showed 20–80 % lethality and only the high ChxA II-producer was statistically more lethal than a non-ChxA-producer, in the mice model assay. ChxA I and II production levels were not well correlated with mice lethality, and this could be due to the heterogeneity of the strains tested.

Conclusion. ChxA I to III was produced mostly extracellularly at various levels depending on strains and culture conditions. The bead-ELISA developed in this study is useful for the detection and quantification of ChxA in

V. cholerae

strains.
Increased vulnerability to SARS-CoV-2 infection among indigenous peoples living in the urban area of Manaus
Authors: Pontes Gemilson Soares , de Melo Silva Jean , Pinheiro-Silva Renato , Barbosa Anderson Nogueira , Santos Luciano Cardenes , de Pádua Quirino Ramalho Antônio , de Castro Alves Carlos Eduardo , da Silva Danielle Furtado , de Oliveira Leonardo Calheiros , da Costa Allyson Guimarães , Bruno Ana Carla
Published: April 2021

Background

The COVID-19 pandemic threatens indigenous peoples living in suburban areas of large Brazilian cities and has thus far intensified their pre-existing socio-economic inequalities. This study evaluated the epidemiological situation of SARS-CoV-2 infection among residents of the biggest urban multiethnic indigenous community of the Amazonas state, Brazil.

Methods

Blood samples of 280 indigenous people who live in the urban community known as Parque das Tribos, which is located in the surrounding area of Manaus, were tested for the presence of anti- SARS-CoV-2 IgA or IgG antibodies using an enzyme-linked immunosorbent assay. An epidemiological standardized interviewer-administered questionnaire was applied to assess the risk factors and sociodemographic information of the study population.

Results

We found a total positivity rate of 64.64% (95% CI 59.01-70.28) for SARS-CoV-2 infection. IgA and IgG were detected in 55.71% (95% CI 49.89-61.54) and 60.71% (95% CI 54.98-66.45) of the individuals tested, respectively. From the total number (n=280), 80.11% of positive individuals (95%; CI 74.24-85.98) were positive for both IgA and IgG Abs. All individuals with COVID-19-related symptoms on the day of blood collection (n=11) were positive for IgG, while IgA was detected in 84.61% (n=55) of individuals who had presented symptoms several weeks before the blood collection. Individuals aged 30-39 were more susceptible to SARS-CoV-2 infection (prevalence ratio [PR] 0.77; 95% CI 0.58-1.03; p=0.033). People whose main source of information on COVID-19 was religious leaders or friends showed higher susceptibility to infection (PR 1.22; 95% CI 1.00-1.49; p=0.040). In addition, individuals who left home more frequently were at higher risk of infection (PR 1.22; 95% CI 1.00-1.49; p=0.048). Five or more individuals per household increased almost 5-fold the risk of virus transmission (Odds ratio [OR] 2.56; 95% CI; 1.09-6.01; p=0.019). Over 95% of the study population had no access to clean water and/or sanitation.

Conclusions

The disproportionate dissemination of SARS-CoV-2 infection observed in the Parque das Tribos urban indigenous community might be driven by typical cultural behavior and socioeconomic inequalities. Despite the pandemic threat, this population is not being targeted by public policies and appears to be chronically invisible to the Brazilian authorities.
Making sense of non-randomized comparative treatment studies in times of Covid-19: A case study of tocilizumab
Authors: Owen Ruth , Qizilbash Nawab , Díaz Sara Velázquez , Vázquez José María Castellano , Pocock Stuart
Published: April 2021

BACKGROUND

Tocilizumab (TCZ) is an interleukin-6 inhibitor and the second established effective drug for the treatment of hospitalized patients with Covid-19. In this study, we sought to validate the recent positive findings from the randomised clinical trial RECOVERY and to evaluate the challenges in the analysis and interpretation of non-randomized comparative effectiveness studies in Covid-19.

METHODS

We performed a retrospective cohort study using an openly available database of hospitalised Covid-19 patients in Spain. The primary outcome was all-cause in-hospital mortality at 28 days. We used multivariable Fine and Gray competing risk models which adjusted for both fixed and time-variant confounders to investigate the effect of TCZ on the primary outcome.

RESULTS

We analysed 2547 patients hospitalised with Covid-19 between 1st January and 28th June 2020. Patients in the TCZ group tended to have more severe Covid-19 at admission, as measured by biomarkers of disease severity including CRP, D-dimer and LDH. At 28 days, 91 out of 440 TCZ patients had died compared to 267 out of 2107 patients in the control group. In multivariable analysis, there was no evidence of an association between TCZ and the primary outcome (adjusted hazard ratio 1.20, 95% CI 0.86 to 1.64, P=0.26).

CONCLUSIONS

Our observational study failed to find a benefit of TCZ on all-cause in-hospital mortality in Covid-19 patients compared with randomized trials, highlighting the impact that unmeasured confounding and other sources of bias can have in a retrospective observational setting. For future observational studies, we recommend prospective data collection to ensure all variables have the necessary quality, completeness and timing for reliable treatment evaluation.
The role of petal transpiration in floral humidity generation
Authors: Harrap Michael J. M. , Rands Sean A.
Published: April 2021

Floral humidity, an area of elevated humidity in the headspace of flowers, has been detected across angiosperms and may function as a pollinator cue for insect pollinators. It is believed floral humidity is produced predominantly through a combination of evaporation of both liquid nectar and transpirational water loss from the flower. However, the role of transpiration in floral humidity generation has not been tested and is largely inferred by continued humidity production when nectar is removed from flowers. Understanding the extent that transpiration contributes to floral humidity has important implications for understanding the function of floral humidity. We test whether transpiration contributes to the floral humidity generation of two species previously identified to produce elevated floral humidity,Calystegia silvaticaandEschscholzia californica. Floral humidity production of flowers that underwent an antitranspirant treatment, petrolatum gel which blocks transpiration from treated tissues, is compared to flowers that did not receive such treatments. Gel treatments reduced floral humidity production to approximately a third of that produced by untreated flowers inC. silvatica, and half of that inE. californica. This confirms, the previously untested, inferences that transpiration has a large contribution to floral humidity generation and that this contribution may vary between species.

HIGHLIGHT

We confirm, the previously untested, inferences that transpiration has a large contribution to floral humidity generation and show that this contribution may vary between species.
Highly parallel genomic selection response in replicatedDrosophila melanogasterpopulations with reduced genetic variation
Authors: Claire Burny , Viola Nolte , Marlies Dolezal , Christian Schlötterer
Published: April 2021

Many adaptive traits are polygenic and frequently more loci contributing to the phenotype than needed are segregating in populations to express a phenotypic optimum. Experimental evolution provides a powerful approach to study polygenic adaptation using replicated populations adapting to a new controlled environment. Since genetic redundancy often results in non-parallel selection responses among replicates, we propose a modified Evolve and Resequencing (E&R) design that maximizes the similarity among replicates. Rather than starting from many founders, we only use two inbredDrosophila melanogasterstrains and expose them to a very extreme, hot temperature environment (29°C). After 20 generations, we detect many genomic regions with a strong, highly parallel selection response in 10 evolved replicates. The X chromosome has a more pronounced selection response than the autosomes, which may be attributed to dominance effects. Furthermore, we find that the median selection coefficient for all chromosomes is higher in our two-genotype experiment than in classic E&R studies. Since two random genomes harbor sufficient variation for adaptive responses, we propose that this approach is particularly well-suited for the analysis of polygenic adaptation.
Bonsai: An efficient method for inferring large human pedigrees from genotype data
Authors: Jewett Ethan M. , McManus Kimberly F. , Freyman William A. ,   the 23andMe Research Team, Auton Adam
Published: April 2021

1.

Abstract

Pedigree inference from genotype data is a challenging problem, particularly when pedigrees are sparsely sampled and individuals may be distantly related to their closest genotyped relatives. We present a new method that infers small pedigrees of close relatives and then assembles them into larger pedigrees. To assemble large pedigrees, we introduce several new formulas and tools including a new likelihood for the degree separating two small pedigrees, a method for detecting individuals who share background identity-by-descent (IBD) that does not reflect recent common ancestry, and a method for identifying the ancestral branches through which distant relatives are connected. Our method also takes several new approaches that help to improve the accuracy and efficiency of pedigree inference. In particular, we incorporate age information directly into the likelihood rather than using ages only for consistency checks and we employ a heuristic branch-and-bound-like approach to more efficiently explore the space of possible pedigrees. Together, these approaches make it possible to construct large pedigrees that are challenging or intractable for current inference methods. The new method, Bonsai, is available athttps://github.com/23andMe/bonsaitree.
Chemogenetically decreasing activity of the dorsal cochlear nucleus can ameliorate noise-induced tinnitus in mice
Authors: Malfatti Thawann , Ciralli Barbara , Hilscher Markus M. , Leao Richardson N. , Leao Katarina E.
Published: April 2021

The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2α(CaMKIIα) positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. Mice were exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence) and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded two days before and two weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKIIα+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKIIα+ DCN units decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKIIα-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKIIα-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice). Our results suggest that CaMKIIα-hM4Di positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.
Using Hierarchical Similarity To Examine The Genetics of Behçet’s Disease
Authors: Shenoi Samuel J , Baker Erich J
Published: April 2021

Behçet’s disease (BD) is a multisystem inflammatory disease that affects patients along the historic silk road. Thus far, the pathogenesis of the disease has proved elusive due to the complex genetic interactions and unknown environmental or viral triggering factors of the disease. In this paper, we seek to clarify the genetic factors of the disease while also uncovering other diseases of interest that present with a similar genotype as BD. To do this, we employ a convergent functional genomics approach by leveraging the hierarchical similarity tool available in Geneweaver. Through our analysis, we were able to ascertain 7 BD consensus genes and 16 autoimmune diseases with genetic overlap with BD. The results of our study will inform further research into the pathogenesis of Behçet’s Disease.
Bacterioplankton diversity and pollution levels in the estuarine regions of Chaliyar and Anjarakkandi rivers, Kerala, India
Authors: Nikhitha D. , Narayanankutty Arunaksharan , Jacob Jisha
Published: April 2021

Rivers and the estuarine regions play crucial roles in the environment by controlling the nutrient cycling, waste disposal, and also in supporting biodiversity. However, the estuarine regions of rivers are highly susceptible to disruptive changes by anthropogenic pollutants and eutrophication. Bacterioplankton diversity is the best indicators of the pollution level and eutrophication status of the rivers. The present study evaluated the eutrophication status and bacterioplankton diversity of the estuarine regions of Chaliyar and the Anjarakkandi originated from the Western Ghats. The present study observed the presence of increased incidence of bacterioplankton comprising of proteobacteria, actinobacteria and cyanobacteria in the estuarine regions of Anjarakkandi river compared to that of Chaliyar river. Further, the percentage incidence of faecal bacteria including Bacillus subtilis and E. coli, were also found to be in high in the Anjarakkandi river; in corroborating with this, the diversity of nitrogen metabolizing bacteria was also higher in the estuarine samples of Anjarakkandi river. Corroborating with this, the levels of water nutrients including nirates, nitrites and phosphates were high in the Anjarakkandi compared to the Chaliyar river. Together, it is possible that there might be increased faecal contamination and subsequent increased eutrophication in the estuarine regions of Anjarakkandi river. Altogether, the study concludes that the Anjarakkandi river may be more polluted and which is partly contributed by faecal contaminants and also responsible for the change in the bacterioplankton community of the estuaries.
Systematic review of the entomological impact of insecticide-treated nets evaluated using experimental hut trials in Africa
Authors: Nash Rebecca K , Lambert Ben , N’Guessan Raphael , Ngufor Corine , Rowland Mark , Oxborough Richard , Moore Sarah , Tungu Patrick , Sherrard-Smith Ellie , Churcher Thomas S
Published: April 2021

Background

Resistance of anopheline mosquitoes to pyrethroid insecticides is spreading rapidly across sub-Saharan Africa, diminishing the efficacy of insecticide-treated nets (ITNs) — the primary tool for preventing malaria. The entomological efficacy of indoor vector control interventions can be measured in experimental hut trials (EHTs), which are specially designed to quantify the protection provided under controlled conditions. Experimental hut structures resemble local housing but allow collection of surviving exiting mosquitoes as well as dead or dying mosquitoes. There is a need to understand how the spread of resistance changes ITN efficacy and to elucidate factors influencing EHT results, including differences in experimental hut construction and design features, to support the development of novel vector control tools.

Methods

A comprehensive database of EHTs was compiled and summarised following a systematic review to identify all known trials investigating ITNs or indoor residual spraying (IRS) across sub-Saharan Africa. This analysis focuses on EHTs investigating ITNs and uses Bayesian statistical models to characterise the complex interaction between ITNs and mosquitoes, the variability between studies, and the impact of pyrethroid resistance.

Results

As resistance rises, the entomological efficacy of ITNs declines. They induce less mortality and are less likely to deter mosquitoes from entering huts. Despite this, ITNs continue to offer considerable personal protection by reducing mosquito feeding until resistance reaches high levels. There are clear associations between the different entomological impacts of ITNs, though there is still substantial variability between studies, some of which can be accounted for by hut design. The relationship between EHT outcomes and the level of resistance (as measured by discriminating dose bioassays) is highly uncertain.

Conclusions

The meta-analyses show that EHTs are an important reproducible assay for capturing the complex entomological efficacy of ITNs on blood-feeding mosquitoes. The impact of pyrethroid resistance on these measures appears broadly consistent across a wide geographical area once hut design is accounted for, suggesting results can be extrapolated beyond the sites where the trials were conducted. Further work is needed to understand factors influencing EHT outcomes and how the relationship between outcomes and resistance varies when different methods are used to assess the level of resistance in wild mosquito populations. This will allow more precise estimates of the efficacy of these important vector control tools.
The immunomodulatory dCache chemoreceptor TlpA ofHelicobacter pyloribinds multiple attractant and antagonistic ligands via distinct sites
Authors: Johnson Kevin S. , Elgamoudi Bassam , Jen Freda E.-C. , Day Christopher , Sweeney Emily Goers , Pryce Megan L. , Guillemin Karen , Haselhorst Thomas , Korolik Victoria , Ottemann Karen M.
Published: April 2021

TheHelicobacter pylorichemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, and acid. To increase our understanding of TlpA’s sensing profile, we screened for diverse TlpA ligands using ligand binding arrays. TlpA bound seven ligands with affinities in the low to middle micromolar ranges. Three of these ligands, arginine, fumarate, and cysteine, were TlpA-dependent chemoattractants, while the others elicited no response. Molecular docking experiments, site-directed point mutants, and competition surface plasmon resonance binding assays suggested that TlpA binds ligands via both the membrane-distal and -proximal dCache_1 binding pockets. Surprisingly, one of the non-active ligands, glucosamine, acted as a chemotaxis antagonist, preventing the chemotaxis response to chemoattractant ligands and acted to block binding of ligands irrespective of whether they bound the membrane-distal or -proximal dCache_1 subdomains. In total, these results suggest TlpA senses multiple attractant ligands as well as antagonist ones, an emerging theme in chemotaxis systems.

Importance

Numerous chemotactic bacterial pathogens depend on the ability to sense a diverse array of signals through chemoreceptors to achieve successful colonization and virulence within their host. The signals sensed by chemoreceptors, however, are not always fully understood. This is the case for TlpA, a dCache_1 chemoreceptor ofH. pylorithat enables the bacteria to induce less inflammation during chronic infections.H. pyloricauses a significant global disease burden, which is driven by the development of gastric inflammation. Accordingly, it is essential to understand the processes by whichH. pylorimodulates host inflammation. This work uncovers the signals that TlpA can sense and highlights the underappreciated ability for regulating chemotactic responses by antagonistic chemoreceptor ligands, which is an emerging theme among other chemotactic systems.
Engineering paralog-specific PSD-95 synthetic binders as potent and minimally invasive imaging probes
Authors: Rimbault Charlotte , Breillat Christelle , Compans Benjamin , Toulmé Estelle , Vicente Filipe Nunes , Fernandez-Monreal Monica , Mascalchi Patrice , Genuer Camille , Puente-Muñoz Virginia , Gauthereau Isabel , Hosy Eric , Giannone Gregory , Chamma Ingrid , Mackereth Cameron D. , Poujol Christel , Choquet Daniel , Sainlos Matthieu
Published: April 2021

Despite the constant advances in fluorescence imaging techniques, monitoring endogenous proteins still constitutes a major challenge in particular when considering dynamics studies or super-resolution imaging. We have recently evolved specific protein-based binders for PSD-95, the main postsynaptic scaffold proteins at excitatory synapses. Since the synthetic binders recognize epitopes not directly involved in the target protein activity, we consider them here as tools to develop endogenous PSD-95 imaging probes. After confirming their lack of impact on PSD-95 function, we validated their use as intrabody fluorescent probes. We further engineered the probes and demonstrated their usefulness in different super-resolution imaging modalities (STED, PALM and DNA-PAINT) in both live and fixed neurons. Finally, we exploited the binders to enrich at the synapse genetically encoded calcium reporters. Overall, we demonstrate that these evolved binders constitute a robust and efficient platform to selectively target and monitor endogenous PSD-95 using various fluorescence imaging techniques.
Thermal stress induces positive phenotypic and molecular feedback loops in zebrafish embryos
Authors: Feugere Lauric , Scott Victoria F. , Rodriguez-Barucg Quentin , Beltran-Alvarez Pedro , Wollenberg Valero Katharina C.
Published: April 2021

Aquatic organisms must cope with both rising and rapidly changing temperatures. These environmental changes can affect numerous traits, from molecular to ecological scales. Biotic stressors can induce the release of chemical cues which trigger behavioural responses in other individuals. In this study, we infer whether abiotic stressors, such as fluctuating temperature, may similarly propagate stress responses between individuals in fish not directly exposed to the stressor. To test this hypothesis, zebrafish (Danio rerio) embryos were exposed for 24 hours to fluctuating thermal stress, to medium in which another embryo was thermally stressed before (“stress medium”), and to a combination of these. Growth, behaviour, and expression of a panel of genes were used to characterise the thermal stress response and its propagation between embryos. Both high temperatures and stress medium significantly accelerated development and altered embryonic behaviour. Thermal stress significantly decreased the expression of the antioxidant gene SOD1, eight hours after the end of exposure. Of note, we found that the expression of sulfide:quinone oxidoreductase (SQOR), likewise a part of the antioxidant metabolism relevant in vertebrate stress response, and of interleukin-1β (IL-1β), involved in the immune response, were significantly altered by stress medium. This study illustrates the existence of positive thermal stress feedback loops in zebrafish embryos that induce stress in conspecifics. This evidence that thermal stress due to fluctuating, high temperatures can be propagated may be relevant for species found in high densities, either in aquaculture or in the natural environment, in a context of global change.