bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient satisfaction with deep versus light/moderate sedation for non-surgical procedures
Authors: Hoshijima Hiroshi , Higuchi Hitoshi , Sato (Boku) Aiji , Shibuya Makiko , Morimoto Yoshinari , Fujisawa Toshiaki , Mizuta Kentaro
Published: September 2021

Background:

Deep sedation relieves a patient's anxiety and stress during the procedure by inducing patient unconsciousness. However, it remains unclear whether deep sedation actually improves patient satisfaction with the procedure. Therefore, we performed a systematic review and meta-analysis to compare the satisfaction of patients undergoing deep sedation with that of those undergoing light/moderate sedation during non-surgical procedures.

Methods:

A comprehensive literature search was performed using electronic databases (search until September 2020). The primary outcome was whether patient satisfaction was higher after deep sedation or light/moderate sedation. The secondary outcome was the relative safety of deep sedation compared with light/moderate sedation in terms of oxygen saturation, systolic blood pressure, and heart rate. The tertiary outcomes were the relative procedure and recovery times for deep versus light/moderate sedation.

Data from each of the trials were combined, and calculations were made using DerSimonian and Laird random effects models. The pooled effect estimates for patient satisfaction were evaluated using relative risk (RR) with the 95% confidence interval (CI). The pooled effect estimates for continuous data are expressed as weighted mean difference with the 95% CI. We assessed heterogeneity with the Cochrane Q statistic and the I2 statistic. The risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation approach were used as the quality assessment method.

Results:

After removing unrelated studies and applying the exclusion criterion, 5 articles satisfied the inclusion criteria. Patient satisfaction was significantly higher in those who received deep sedation compared with light/moderate sedation (relative risk = 1.12; 95% CI, 1.04–1.20; P = .003; Cochrane Q = 25.0; I2 = 76%).

There was no significant difference in oxygen saturation, systolic blood pressure, heart rate, and procedure times according to whether the procedures were performed under deep or light/moderate sedation. However, the recovery time was significantly prolonged in patients under deep sedation.

Conclusions:

Our meta-analysis suggests that deep sedation resulted in improved patient satisfaction compared with light/moderate sedation. Deep sedation is recommended for patients undergoing procedures because it improves patient satisfaction. However, respiration and circulation should be carefully monitored both intra-operatively and postoperatively.
Factors behind the prevalence of carbapenem-resistant Klebsiella pneumoniae in pediatric wards
Authors: Yang Yuxin , Liu Jia , Muhammad Murad , Liu Hanting , Min Zongsu , Lu Jing , Zhang Lei , Chai Zhonglin
Published: September 2021

The emergence of carbapenem-resistant Enterobacteriaceae made the treatment difficult, which has become a significant issue of public health. A sharp increase of carbapenem-resistance rate in Klebsiella pneumoniae was observed in a maternity and child health care hospital in Zunyi, China, in 2014.

In 2015 to 2016, carbapenem-resistant Klebsiella pneumoniae (CRKp) isolated from all the clinical samples were analyzed to identify the carbapenem-resistance genes. They were then fingerprinted in order to determine their genetic relationship. Clinical data such as usage of imipenem in 2012 to 2016 and the nosocomial infection surveillance data were analyzed.

Thirty-five isolates of CRKp out of 4328 various pathogens were obtained, and bla
NDM-1 was identified to be the most common resistant gene present in the CRKp isolates. The fingerprint analysis identified 15 major clusters of CRKp isolates. The bacteria with close proximity relationship tended to be from the same wards. However, a few CRKp isolates from different wards were found to be genetically highly related. The clinical data showed a significantly higher usage of carbapenems in 2012 to 2013 before the CRKp rate sharply increased in 2014. The nosocomial infection surveillance showed an unexpectedly high rate of failures to meet the requirement of the hospital environment hygiene and hand hygiene in the neonatal ward.

The increasing isolation rate of CRKp was associated with poorly regulated usage of carbapenems, impropriate medical practices, and the poor hospital environmental hygiene and hand hygiene.
Intra-muscular follicular dendritic cell sarcoma in the thigh
Authors: Cho Yong Jin , Han Song Iy , Lim Sung-Chul
Published: September 2021

Rationale:

Follicular dendritic cell sarcoma (FDCS) is an intermediate-grade malignancy originating from follicular dendritic cells. Nodal FDCS is the most common type, meaning that the extranodal type may not be recognized and could be easily misdiagnosed. Reported extranodal sites include the head and neck, retroperitoneum, spleen, liver, and gastrointestinal tract. FDCS in the soft tissue is extremely rare.

Patient concerns:

A 75-year-old male presented with complaints of a localized swelling and intra-muscular soft tissue mass in the left upper thigh.

Diagnosis:

The present tumor consisted of fascicular or vague storiform-arranged spindle cells with less pleomorphism and many lymphoid aggregates. Tumor cells were positive for CD21, CD35, CD68, vimentin, and EGFR. Intra-muscular FDCS was confirmed by immunohistochemical studies.

Interventions:

The patient received a wide marginal excision, followed by adjuvant radiotherapy.

Outcomes:

Symptomatic improvements were achieved and no subsequent relapses were observed.

Lessons:

If the tumor arises in the extranodal sites, especially in the soft tissue, it is difficult to include FDCS in the differential diagnosis. When the immunoprofile is not consistent with that of common spindle cell tumors, immunostaining for follicular dendritic cell markers such as CD21, CD23, and CD35, as well as further immunohistochemistry for D2-40, CD68, EGFR, Epstein-Barr virus, and BRAF can be helpful for the diagnosis and subtyping of FDCS. To the best of our knowledge, the present case is the first case of intramuscular FDCS.
Long-term effects of endoscopic papillary large balloon dilation in patients with challenging bile duct calculi
Authors: Kamezaki Hidehiro , Iwanaga Terunao , Maeda Takahiro , Senoo Jun-ichi , Sakamoto Dai , Yasui Shin , Sugiyama Harutoshi , Tsuyuguchi Toshio , Kato Naoya
Published: September 2021

Endoscopic papillary large balloon dilation (EPLBD) can be used to treat challenging common bile duct stones. No previous studies have reported intractable cases treated either by EPLBD or mechanical lithotripter use. We aimed to evaluate and compare the long-term effects of EPLBD with mechanical lithotripter use.

This retrospective cohort study reviewed data from 153 patients admitted to the Eastern Chiba Medical Center from April 2014 to March 2020, presenting with common bile duct calculi that could not be removed using a basket or balloon catheter. Patients were divided into groups depending on whether the treatment was performed using a mechanical lithotripter or EPLBD. The primary outcome was the recurrence rate of common bile duct calculi, and the secondary outcome was the rate of postoperative adverse events. The Wilcoxon test was used to compare the 2 groups. Statistical significance was set at P < .05.

The median age of patients included in the lithotripter and EPLBD groups were 73 years and 83 years, respectively (P = .006), while the sex ratio (male:female) in the groups was 18:13 and 55:67, respectively. The EPLBD group showed a statistically larger median bile duct diameter (13 mm [range: 8–24 mm] vs 11 mm [range: 5–16 mm]; P < .001), larger maximal calculus diameter (median, 13.5 mm [range: 8–25 mm] vs 11 mm [range: 7–16 mm]; P < .001), and shorter median cumulative treatment time after reaching the duodenal papilla (35.5 minutes [range: 10–176 minutes] vs 47 minutes [range: 22–321 minutes]; P = .026) in comparison to the lithotripter group. There was no significant difference in the rate of adverse events between the EPLBD and the mechanical lithotripter groups. The recurrence rate was significantly lower (P = .014) in the EPLBD group.

EPLBD increases therapeutic efficacy and reduces treatment duration for patients in whom calculus removal is difficult, without increasing the frequency of adverse events. No serious adverse events were observed. Additionally, EPLBD appears to reduce the risk of long-term recurrence. Future studies are needed to evaluate long-term outcomes in younger patients.
Psychosocial Stress, Social Support, and the Escalation of Schizotypal Symptoms
Authors: Juan Michael A. , Rosenfarb Irwin Ford
Published: September 2021

Although research suggests that psychosocial stress is associated with an increase in schizotypal symptoms, the type of stressor associated with increased symptomatology is unclear, and no study has examined whether social support might mitigate the effects of stress on symptom change. In this study, 131 young adults completed measures of schizotypal symptoms, major life events, daily hassles, and perceptions of social support at baseline, and measures of stress and symptoms again 4 to 6 weeks later. Results indicated, after controlling for baseline measures, that for those scoring low on schizotypal measures at baseline, only low levels of social support were associated with increased symptoms. For those scoring high on the schizotypal scales at baseline, however, both major life events and daily hassles were associated with increased symptomatology, but only when perceptions of social support at baseline were low. The results suggest that it is important to assess both perceptions of social support and baseline symptomatology when examining whether major life events and daily stress are associated with increased psychotic symptoms. Both types of psychosocial stress are associated with an increase in symptoms, but only for those who are already showing above average symptoms and only when social support is low.
99mTc-MIBI SPECT/CT and FDG PET/CT in Isolated Bilateral Renal Metastases From Adenoid Cystic Carcinoma of the Maxilla
Authors: Zhao Qian , Dong Aisheng , Ye Huamao , Zuo Changjing
Published: September 2021

Renal metastasis from adenoid cystic carcinoma of the head and neck is uncommon. We present 99mTc-MIBI SPECT/CT and FDG PET/CT findings in a case with isolated bilateral renal metastases from adenoid cystic carcinoma of the left maxilla. The metastatic adenoid cystic carcinomas of the kidneys showed photopenia on 99mTc-MIBI SPECT/CT and increased FDG uptake on FDG PET/CT mimicking primary renal cell carcinoma.
Impact of Follow-up 18F-FDG PET on the Management in Patients With Lung Cancer
Authors: Yoon Hai-Jeon , Pak Kyoungjune
Published: September 2021

Purpose

The incidence of lung cancer has increased steadily. We meta-analyzed to assess the impact of 18F-FDG PET on the management of lung cancer to detect recurrence/metastasis.

Materials and Methods

We performed systematic searches of Medline and Embase databases for English-language publications. All published studies regarding the impact of PET on the management of patients with lung cancer in detection of recurrence/metastasis were searched. The proportion of management change (%) defined as the percentage of patients who changed management after FDG PET to patients who had FDG PET was calculated. The data from each study were analyzed using MedCalc Statistical Software version 14.12.0 (MedCalc Software, Ostend, Belgium).

Results

Eight studies including 523 patients were eligible for inclusion in the study. The impact of 18F-FDG PET for the purpose of detecting recurrence/metastasis in patients with lung cancer was evaluated using management change rates, which were ranged from 28.6% to 79.2% with a pooled effect of 61.4% (95% confidence interval, 49.5%–72.7%; I
2 = 85.7%). In a subgroup analysis, impact of 18F-FDG PET was evaluated in studies of patients with non–small cell lung cancer with indication of abnormal findings of conventional imaging, elevated tumor markers, and clinical symptoms with the pooled rate of management change of 62.2% (95% confidence interval, 44.2%–78.5%; I
2 = 88.0%).

Conclusions

We have highlighted that 18F-FDG PET has a major impact on the management of patients with recurrent lung cancer. These findings suggest that 18F-FDG PET should be performed in patients with lung cancer, especially in cases involving equivocal or suspicious recurrence/metastasis on conventional imaging, elevated tumor markers, or clinical symptoms during follow-up.
Recurrence of a Pheochromocytoma With TNEM127 Mutation Negative on 18F-FDOPA and 18F-FDG but Positive on 123I-MIBG and 68Ga-DOTATOC Imaging
Authors: Cottereau Anne-Ségolène , Garcia Cyril , Dousset Bertrand , Libe Rossella , Tenenbaum Florence
Published: September 2021

We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.
Supraclavicular and Axillary Lymphadenopathy Induced by COVID-19 Vaccination on 18F-Fluorthanatrace, 68Ga-DOTATATE, and 18F-Fluciclovine PET/CT
Authors: Surasi Devaki Shilpa Sudha , Lin Lilie , Ravizzini Gregory , Wong Franklin
Published: September 2021

COVID-19 vaccination has started in most countries, and postvaccination imaging is inevitable in the oncologic population. The immune response to the vaccination in the form of reactive lymphadenopathy has been well documented on 18F-FDG PET/CT. We present the imaging findings of 3 patients who have undergone non-FDG PET/CT imaging including 18F-fluorthanatrace, 68Ga-DOTATATE, and 18F-fluciclovine PET/CT. It is crucial to recognize the timing and laterality of immunization to avoid false-positive findings.
Key Role of Personalized Dosimetry in Dose Adjustment for Selective Internal Radiotherapy
Authors: Subreville Celine , Pinaquy Jean-Baptiste , Lapuyade Bruno , Blanc Jean-Frederic , Bordenave Laurence , Papadopoulos Panteleimon , Debordeaux Frederic
Published: September 2021

Purpose

Selective internal radiotherapy with 90Y microspheres is widely used for the treatment of patients with liver cancer. A dosimetric analysis using the dosimetry software Simplicit90y (Boston Scientific, Natick, MA) was conducted to define doses to the tumor and healthy liver, and to determine a threshold tumor dose that could predict progression-free survival.

Methods

Patients experiencing hepatocellular carcinoma and treated with 90Y-labeled resin microspheres were included in a retrospective study. The time-to-progression of the target lesions (TTPLs) and overall survival (OS) were evaluated using Kaplan-Meier tests, and this comparison was based on a log-rank test.

Results

Twenty-four procedures for patients with portal vein thrombosis were realized. Median follow-up was 16 months. A threshold tumor dose of 125 Gy was determined with a sensitivity of 89% and a specificity of 100%. For patients with a tumor dose of less than 125 Gy, the median OS was 7.5 months (95% confidence interval [CI], 5–14 months) and the TTPL was 3 months (95% CI, 2–6 months) versus 33 months (95% CI, 22–39 months) and 23 months (95% CI, 7–38 months), respectively, for those with a tumor dose of 125 Gy or more (P = 0.002 and P = 0.0004).

Conclusions

Personalized dosimetry based on 99mTc-MAA SPECT/CT is predictive of TTPL and OS in patients with hepatocellular carcinoma. Customized dosimetry software is essential to optimize treatment planning.
Immunotherapy (Cemiplimab)-Induced Bullous Pemphigoid
Authors: Grünig Hannes , Skawran Stephan M. , Nägeli Mirjam , Kamarachev Jivko , Huellner Martin W.
Published: September 2021

A 78-year-old man with multiple squamous cell carcinomas of the skin underwent 18F-FDG-PET/CT for restaging after 4 cycles of cemiplimab. The scan showed new disseminated FDG-avid skin lesions. Dermatologic examination and biopsy revealed bullous pemphigoid. Discontinuation of cemiplimab and treatment with corticosteroids led to clinical improvement, after which treatment with cemiplimab was resumed. A broad spectrum of inflammatory adverse events can occur in patients treated with immune checkpoint inhibitors, and FDG avidity of these lesions may mimic metastases. Knowledge of such imaging pitfalls is essential for interpreting 18F-FDG-PET/CT, particularly if they occur in the same organ as the primary tumor.
Effect of Remote Cardiac Monitoring System Design on Response Time to Critical Arrhythmias
Authors: Segall Noa , Joines Jeffrey A. , Baldwin Ron'Nisha D. , Bresch Diane , Coggins Lauren G. , Janzen Suzanne , Engel Jill R. , Wright Melanie C.
Published: September 2021

Introduction

In many hospitals across the country, electrocardiograms of multiple at-risk patients are monitored remotely by telemetry monitor watchers in a central location. However, there is limited evidence regarding best practices for designing these cardiac monitoring systems to ensure prompt detection and response to life-threatening events. To identify factors that may affect monitoring efficiency, we simulated critical arrhythmias in inpatient units with different monitoring systems and compared their efficiency in communicating the arrhythmias to a first responder.

Methods

This was a multicenter cross-sectional in situ simulation study. Simulation participants were monitor watchers and first responders (usually nurses) in 2 inpatient units in each of 3 hospitals. Manipulated variables included: (1) number of communication nodes between monitor watchers and first responders; (2) central monitoring station location—on or off the patient care unit; (3) monitor watchers' workload; (4) nurses' workload; and (5) participants' experience.

Results

We performed 62 arrhythmia simulations to measure response times of monitor watchers and 128 arrhythmia simulations to measure response times in patient care units. We found that systems in which an intermediary between monitor watchers and nurses communicated critical events had faster response times to simulated arrhythmias than systems in which monitor watchers communicated directly with nurses. Responses were also faster in units colocated with central monitoring stations than in those located remotely. As the perceived workload of nurses increased, response latency also increased. Experience did not affect response times.

Conclusions

Although limited in our ability to isolate the effects of these factors from extraneous factors on central monitoring system efficiency, our study provides a roadmap for using in situ arrhythmia simulations to assess and improve monitoring performance.
Laparoscopic-assisted Open Pyloroduodenostomy Repair of Pyloric Atresia in an Infant: A Rare Congenital Anomaly
Authors: Huerta Carlos Theodore , Sundin Andrew , Gilna Gareth P. , Saberi Rebecca A. , Ramsey Walter A. , O’Neil Christopher F. , Brady Ann-Christina , Perez Eduardo A.
Published: September 2021

Purpose:

Pyloric atresia is an uncommon congenital anomaly that may present with emesis and dehydration early in infancy. Definitive therapy consists of pyloroplasty or gastroduodenostomy depending on the subtype of atresia involved.

Case Presentation:

We report the case of a 2-day-old girl infant who presented with nonbilious emesis with feeds. Abdominal ultrasound and upper gastrointestinal series were performed and demonstrated a dilated, air-filled stomach with no distal air or passage of contrast. The patient was successfully treated by laparoscopic-assisted open pyloroduodenostomy of a type 2 pyloric atresia.

Conclusion:

Type 2 pyloric atresia is a rare clinical entity that can present with symptoms of gastric outlet obstruction. The patient described was treated by laparoscopic-assisted open pyloroduodenostomy, which has not been previously described for pyloric atresia. This work demonstrates an example of the safety and efficacy of laparoscopic surgery for infants with this anomaly.
Reducing Domain Shift For Mitosis Detection Using Preprocessing Homogenizers
Authors: Almahfouz Nasser Sahar , Cherian Kurian Nikhil , Sethi Amit
Published: September 2021

The detection of mitotic figures in histological tumor images plays a vital role in the decision-making of the appropriate therapy. However, tissue preparation and image acquisition methods degrade the performances of the deep learning-based approaches for mitotic figures detection. MItosis DOmain Generalization challenge addresses the domain-shift problem of this detection task. This work presents our approach based on preprocessing homogenizers to tackling this problem.
Is academic medicine prepared to teach about the intersection of childhood experiences and health across the life course? An exploratory survey of faculty
Authors: Koo Angie , Irwin Jordyn , Sturgis Morgan , Schwartz Alan , Hasnain Memoona , Davis Elizabeth , Stillerman Audrey
Published: September 2021

Purpose

Childhood experiences affect health across the lifespan. Evidence-based prevention and treatment strategies targeting early-life stress are emerging. Nevertheless, faculty physicians’ preparation to incorporate this science into practice has not been well studied. The purpose of this study was to explore medical faculty knowledge and beliefs, timing and route of knowledge acquisition, perceived relevance and application of topics, and any associated faculty characteristics.

Method

The research team developed and administered a 39-question survey to faculty from six departments at the University of Illinois College of Medicine and Rush Medical College in Chicago. The team employed quantitative and qualitative methods to analyze responses.

Results

Eighty-one (8.8%) eligible faculty completed the survey. Of respondents, 53 (65.4%) achieved a high score on knowledge questions, 34 (42.0%) on beliefs questions, and 42 (59.1%) described high concept exposure, but only six (7.4%) through a formal route. Although 78 (96.8%) respondents indicated that survey concepts are relevant, only 18 (22.2%) reported fully incorporating them in their work. Respondents reporting full incorporation of concepts were significantly more likely to attain high concept exposure scores than those not fully incorporating concepts (17 respondents, 94.4%, vs. 25 respondents, 39.7 %, P < .001), whether reporting formal or informal exposure. Both quantitative and qualitative analysis highlighted limited awareness among respondents of trauma prevalence among healthcare workers, lack of familiarity with interventions, and challenges in addressing childhood experiences given time and resource constraints.

Conclusions

Most respondents had some familiarity with the impact of childhood experiences on health and perceived the relevance of this science. Nonetheless, many identified the need for additional coaching. Because results suggest that exposure supports full application of concepts, intentional faculty development and establishment of medical education competencies is pivotal to prepare faculty to include these crucial topics in patient care and teaching.
Prevalence of anti-SARS-CoV-2 immunity in Kazakhstan before the launch of COVID-19 vaccination
Authors: Kadyrova Irina , Yegorov Sergey , Negmetzhanov Baurzhan , Kolesnikova Yevgeniya , Kolesnichenko Svetlana , Korshukov Ilya , Vazenmiller Dmitriy , Stupina Yelena , Kabildina Naylya , Ashimova Assem , Raimbekova Aigul , Turmukhambetova Anar , Miller Matthew S. , Hortelano Gonzalo , Babenko Dmitriy
Published: September 2021

Background

COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, we assessed the prevalence of anti-SARS-CoV-2 antibody-mediated immunity in a heterogeneous cohort of public university employees in Karaganda, Kazakhstan.

Methods

Asymptomatic subjects (n=100) were recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used to validate the assay positivity thresholds.

Results

Anti-S IgG and IgA seropositivity rates among SARS-CoV-2 PCR-negative participants (n=100) were 42% (95% CI [32.2-52.3]) and 59% (95% CI [48.8-69.0]), respectively, and 64% (95% CI [53.4-73.1]) of the cohort tested positive for at least one of the antibodies. Anti-S IgG titres correlated with virus neutralization activity, detectable in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history of COVID-19 was associated with Kazakh ethnicity and self-reported history of respiratory illness since March 2020.

Conclusions

SARS-CoV-2 exposure in this cohort is ∼15-fold higher compared to the reported all-time national and regional COVID-19 prevalence. Continuous serological surveillance is critical for understanding the COVID-19 transmission dynamics and should be nationally implemented to better inform the public health response in Central Asia.
metaCOVID:An R-Shiny application for living meta-analyses of COVID-19 trials
Authors: Evrenoglou Theodoros , Boutron Isabelle , Chaimani Anna
Published: September 2021

“Living” evidence synthesis is of primary interest for decision-makers to overcome the COVID-19 pandemic. The COVID-NMA provides open-access living meta-analyses assessing different therapeutic and preventive interventions. Data are posted on a platform (https://covid-nma.com/) and analyses are updated every week. However, guideline developers and other stakeholders also need to investigate the data and perform their own analyses. This requires resources, time, statistical expertise, and software knowledge. To assist them, we created the “metaCOVID”application which, based on automation processes, facilitates the fast exploration of the data and the conduct of analyses tailored to end-users needs.metaCOVIDhas been created in R and is freely available as an R-Shiny application. The application conducts living meta-analyses for every outcome. Several options are available for subgroup and sensitivity analyses. The results are presented in downloadable forest plots.metaCOVIDis freely available fromhttps://covid-nma.com/metacovid/and the source code fromhttps://github.com/TEvrenoglou/metaCovid.
Methylothon: a versatile course-based high school research experience in microbiology and bioinformatics-- with pink bacteria
Authors: Jones Peyton A. , Frischer David , Mueller Shannon , Le Thomas , Schwanes Anya , Govindaraju Alekhya , Shalvarjian Katie , Leducq Jean-Baptiste , Marx Christopher J. , Martinez-Gomez N. Cecilia , Lee Jessica A.
Published: September 2021

Methylothon is an inquiry-based high school learning module in microbial ecology, molecular biology, and bioinformatics that centers around pink-pigmented plant-associated methylotrophic bacteria. Here we present an overview of the module’s learning goals, describe course resources (available for public use on http://methylothon.com), and relate lessons learned from adapting Methylothon for remote learning during the pandemic in spring of 2021. The original in-person version of the module allows students to isolate their own strains of methylotrophic bacteria from plants they sample from the environment, to identify these using PCR, sequencing, and phylogenetic analysis, and to contribute their strains to original research in a university lab. The adapted version strengthens the focus on bioinformatics and increases its flexibility and accessibility by making the lab portion optional and adopting free web-based tools. Student feedback and graded assignments from Spring 2021 revealed that the lesson was especially effective at introducing the concepts of BLAST and phylogenetic trees, and that students valued and felt inspired by the opportunity to conduct hands-on work and to participate in community science.
A HYPOMETABOLIC DEFENSE STRATEGY AGAINSTPLASMODIUMINFECTION
Authors: Ramos Susana , Ademolue Temitope W. , Jentho Elisa , Wu Qian , Guerra Joel , Martins Rui , Pires Gil , Weis Sebastian , Carlos Ana Rita , Mahú Inês , Seixas Elsa , Duarte Denise , Rajas Fabienne , Cardoso Sílvia , Sousa António G. G. , Lilue Jingtao , Mithieux Gilles , Nogueira Fátima , Soares Miguel P.
Published: September 2021

Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal presentation ofPlasmodium falciparuminfection of humans. Here we report that mice reduce blood glucose levels in response toPlasmodiuminfection via a coordinated response whereby labile heme, an alarmin produced via hemolysis, induces anorexia and represses hepatic glucose production (HGP). While protective against unfettered immune-mediated inflammation, organ damage and anemia, when sustained over time heme-driven repression of HGP can progress towards hypoglycemia, compromising host energy expenditure and thermoregulation. This hypometabolic state arrests the development of asexual stages ofPlasmodium spp., which undergo pyknosis and develop mitochondrial dysfunction. In response,Plasmodiumactivates a transcriptional program reducing its virulence and inducing sexual differentiation towards the production of transmissible gametocytes. We infer that malaria-associated hypoglycemia represents a trade-off of an evolutionarily conserved defense strategy restrictingPlasmodium spp. from accessing host-derived glucose and balancing parasite virulence and transmission.
‘rbioacc’: an ‘R’-package to analyze toxicokinetic data
Authors: Ratier A. , Baudrot V. , Kaag M. , Siberchicot A. , Lopes C. , Charles S.
Published: September 2021

‘rbioacc’ is an ‘R’-package dedicated to the analysis of experimental data collected from bioaccumulation tests during which organisms are exposed to a chemical (exposure phase) and then put into a clean media (depuration phase). Internal concentrations are regularly measured over time all along the experiment.

‘rbioacc’ provides ready-to-use functions to visualize and fully analyze such data. Under a Bayesian framework, this package fits a generic one-compartment toxicokinetic (TK) model automatically built from the data. It provides TK parameter estimates (appropriate uptake and elimination rates) and bioaccumulation metrics (e.g., BCF, BSAF, BMF). All parameter estimates, bioaccumulation metrics as well as predictions of internal concentrations into organisms are delivered with their uncertainty.

Bioaccumulation metrics are primarily provided in support of environmental risk assessment, in full compliance with regulatory requirements required to approve marketing applications of chemical substances.

This paper gives brief worked examples of the use of ‘rbioacc’ from data collected through standard bioaccumulation tests, and publicly available within the scientific literature. These examples constitute step-by-step user-guides to analyze any new data set, uploaded in the right format.
Parkinson’s Disease-Associated, Sex-specific Changes in DNA Methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in Cortical Neurons
Authors: Kochmanski Joseph , Kuhn Nathan C. , Bernstein Alison I.
Published: September 2021

Evidence for epigenetic regulation playing a role in Parkinson’s disease (PD) is growing, particularly for DNA modifications. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA modifications in PD, but none accounted for cell-type or sex in their analyses. Given the hetereogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this first genome-wide analysis of DNA methylation in an enriched neuronal population from PD post-mortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance.
Genome assembly and annotation of the tambaqui (Colossoma macropomum): an emblematic fish of the Amazon River basin
Authors: Hilsdorf Alexandre Wagner Silva , Uliano-Silva Marcela , Coutinho Luiz Lehmann , Montenegro Horácio , Almeida-Val Vera Maria Fonseca , Pinhal Danillo
Published: September 2021

Colossoma macropomum known as “tambaqui” is the largest Characiformes fish in the Amazon River Basin and a leading species in Brazilian aquaculture and fisheries. Good quality meat and great adaptability to culture systems are some of its remarkable farming features. To support studies into the genetics and genomics of the tambaqui, we have produced the first high-quality genome for the species. We combined Illumina and PacBio sequencing technologies to generate a reference genome, assembled with 39X coverage of long reads and polished to a QV=36 with 130X coverage of short reads. The genome was assembled into 1,269 scaffolds to a total of 1,221,847,006 bases, with a scaffold N50 size of 40 Mb where 93% of all assembled bases were placed in the largest 54 scaffolds that corresponds to the diploid karyotype of the tambaqui. Furthermore, the NCBI Annotation Pipeline annotated genes, pseudogenes, and non-coding transcripts using the RefSeq database as evidence, guaranteeing a high-quality annotation. A Genome Data Viewer for the tambaqui was produced which benefits any groups interested in exploring unique genomic features of the species. The availability of a highly accurate genome assembly for tambaqui provides the foundation for novel insights about ecological and evolutionary facets and is a helpful resource for aquaculture purposes.
STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing
Authors: Sun Dongqing , Liu Zhaoyang , Li Taiwen , Wu Qiu , Wang Chenfei
Published: September 2021

The recent advances in spatial transcriptomics have brought unprecedented opportunities to understand the cellular heterogeneity in the spatial context. However, the current limitations of spatial technologies hamper the exploration of cellular localizations and interactions at single-cell level. Here, we present spatial transcriptomics deconvolution by topic modeling (STRIDE), a computational method to decompose cell types from spatial mixtures by leveraging topic profiles trained from single-cell transcriptomics. STRIDE accurately estimated the cell-type proportions and showed balanced specificity and sensitivity compared to existing methods. We demonstrate STRIDE’s utility by applying it to different spatial platforms and biological systems. Deconvolution by STRIDE not only mapped rare cell types to spatial locations but also improved the identification of spatial localized genes and domains. Moreover, topics discovered by STRIDE were associated with cell-type-specific functions, and could be further used to integrate successive sections and reconstruct the three-dimensional architecture of tissues. Taken together, STRIDE is a versatile and extensible tool for integrated analysis of spatial and single-cell transcriptomics and is publicly available athttps://github.com/wanglabtongji/STRIDE.
Specialization of the photoreceptor transcriptome bySrrm3-dependent microexons is required for outer segment maintenance and vision
Authors: Ciampi Ludovica , Mantica Federica , Lopez-Blanch Laura , Rodríguez-Marin Cristina , Cianferoni Damiano , Zang Jingjing , Permanyer Jon , Jiménez-Delgado Senda , Bonnal Sophie , Miravet-Verde Samuel , Ruprecht Verena , Neuhauss Stephan C.F. , Banfi Sandro , Carrella Sabrina , Serrano Luis , Head Sarah A. , Irimia Manuel
Published: September 2021

Retinal photoreceptors differ in their transcriptomic profiles from other neuronal subtypes, likely as a reflection of their unique cellular morphology and function in the detection of light thorough the ciliary outer segment. We discovered a new layer of this molecular specialization by revealing that the vertebrate retina expresses the largest number of tissue-enriched microexons of all tissue types. A subset of these microexons is included exclusively in photoreceptor transcripts, particularly in genes involved in cilia biogenesis and in vesicle-mediated transport. This microexon program is regulated bySrrm3, a paralog of the neural microexon regulatorSrrm4. Despite both proteins positively regulate retina microexonsin vitro, onlySrrm3is highly expressed in mature photoreceptors and its deletion in zebrafish results in widespread downregulation of microexon inclusion, severe photoreceptor alterations and blindness. These results shed light into photoreceptor’s transcriptomic specialization and functionality, uncovering new cell type-specific roles forSrrm3and microexons with implication for retinal diseases.
Feasibility of Administering Human Pancreatic Cancer Chemotherapy in a Spontaneous Pancreatic Cancer Mouse Model
Authors: Delahoussaye Abagail M. , Jaoude Joseph Abi , Fujimoto Tara N. , Molkentine Jessica , Garcia Garcia Carolina J. , Gay Jason P. , Feng Ningping , Marszalek Joe , Taniguchi Cullen M.
Published: September 2021

Background

Both modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel chemotherapy regimens have been shown to improve clinical outcomes in patients with pancreatic cancer, and are often used interchangeably as the standard of care. Preclinical studies often do not use these regimens, since administering these multiagent approaches can be difficult. In this study, we assessed the feasibility of administering these two chemotherapy regimens in spontaneous pancreatic tumors using KPC mice with the ultimate goal of advancing preclinical studies.

Methods

KPC mice were created by breeding KrasLSL-G12D/+ to Trp53fl/fl;Ptf1αCre/+, resulting in KrasLSL-G12D/+;p53fl/+;Ptf1αCre/+ mice. At 14 weeks of age, mice were palpated for spontaneous tumor growth that was verified using ultrasounds. Mice with tumors under 15 mm in diameter were used. The mice were assigned to one of seven treatment regimens: 1 cycle of mFOLFIRINOX (FFX X1), 2 cycles of mFOLFIRINOX (FFX X2), 1 cycle of mFOLFIRINOX with 40Gy SBRT (FFX SBRT), 1 cycle of gemcitabine/nab-paclitaxel (GEM/AB X1), 2 cycles of gemcitabine/nab-paclitaxel (GEM/AB X2), 2 cycles of gemcitabine/nab-paclitaxel with 40Gy SBRT (GEM/AB SBRT), or no chemotherapy treatment (control).

Results

In total, 92 mice were included. The median OS in the FFX X2 group was slightly longer that the median OS in the FFX X1 group (15 days vs 11 days, P=0.003). Mice in the GEM/AB X2 group had longer OS when compared to mice in the GEM/AB X1 group (33.5 vs 13 days, P=0.001). Mice treated with chemotherapy survived longer than untreated control animals (median OS: 6.5 days, P <0.001). Moreover, in mice treated with chemotherapy, mice that received 2 cycles of GEM/AB X2 had the longest survival, while the FFX X1 group had the poorest OS (P <0.001). Lastly, chemotherapy followed by consolidative SBRT trended towards increased local control and survival.

Conclusions

We demonstrate the utility and feasibility of clinicall relevant mFOLFIRINOX and gemcitabine/nab-paclitaxel in preclinical models of pancreatic cancer.
Malayan kraits (Bungarus candidus) show affinity to anthropogenic structures in a human dominated landscape
Authors: Hodges Cameron Wesley , Marshall Benjamin Michael , Hill Jacques George , Strine Colin Thomas
Published: September 2021

Animal movement can impact human-wildlife conflict through a variety of features: increased movement can lead to greater chance of encounter, remaining still can lead to greater or lesser detection, and activity can modulate their impact on humans. Here we assess the movement and space use of the highly venomous and medically important Malayan krait (Bungarus candidus) on a suburban university campus. We radio- tracked 14 kraits for an average of 114 days (min: 19, max: 218), with an average of 106 fixes (min: 21, max: 229). We assessed movement pathways and activity with dynamic Brownian Bridge Movement models, evaluated patterns of revisitation to identify site fidelity, and determined whether individuals selected for particular land-use types with Integrated Step Selection Functions. Most individuals displayed some level of attraction to buildings (n = 10) and natural areas (n = 12); we identified a similar unambiguous pattern of attraction to buildings and natural areas at the population level (of our sample). Snakes remained in shelter sites for long periods of time (max = 94 days) and revisited sites on average every 15.45 days. Over 50% of fixes were within human settlements and 37.1% were associated with buildings. We found generally seasonal patterns of activity, with higher activity in wet seasons (when classes are typically in session on campus), and lower activity in the hot season (when there are a number of short breaks causing students to leave campus). These results show frequent proximity between Malayan kraits and humans at Suranaree University of Technology, Thailand; thereby, suggesting a near constant potential for human- wildlife conflict. Despite the fact that no snakebites from this species occurred at the university during our study period, substantial education and awareness training should be considered to raise awareness to ensure continued coexistence on campus.
APIR: Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control
Authors: Chen Yiling Elaine , Ge Xinzhou , Woyshner Kyla , McDermott MeiLu , Manousopoulou Antigoni , Ficarro Scott B. , Marto Jarrod A. , Li Kexin , Wang Leo David , Li Jingyi Jessica
Published: September 2021

Advances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs. However, no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and control on the false discovery rate (FDR). To fill in this gap, we propose a statistical framework, Aggregation of Peptide Identification Results (APIR), that is universally compatible with all database search algorithms. Notably, under an FDR threshold, APIR is guaranteed to identify at least as many, if not more, peptides as individual database search algorithms do. Evaluation of APIR on a complex proteomics standard shows that APIR outpowers individual database search algorithms and empirically controls the FDR. Real data studies show that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search algorithms. The APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis, e.g., differential gene expression analysis on RNA sequencing data. The APIR R package is available athttps://github.com/yiling0210/APIR.
Vestibular CCK signaling drives motion-induced malaise
Authors: Machuca-Márquez Pablo , Sánchez-Benito Laura , Menardy Fabien , Urpi Andrea , Girona Mònica , Puighermanal Emma , Appiah Isabella , Palmiter Richard , Sanz Elisenda , Quintana Albert
Published: September 2021

Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS- related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activateCalca- expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment.

SIGNIFICANCE STATEMENT

We live in an age where travel is paramount. However, one of the most disabling conditions inherent to traveling is motion sickness (MS). While studies have underscored the role of the vestibular system in the development of MS, the neuronal populations involved in motion-induced malaise remain largely unknown.

Here, we describe the vestibular pathways eliciting MS responses, and identify a key role for cholecystokinin (CCK)-expressing vestibular neurons. We reveal that a vestibulo-parabrachial (PBN) CCKergic projection is sufficient to induce conditioned taste aversion, likely through the activation of calcitonin gene-related peptide-expressing PBN neurons. Finally, we underscore the role of CCK-A receptor signaling as a novel druggable target to treat MS, providing novel insight on the neurobiological substrates of MS.