bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome
Authors: Rokkas Theodore , Hold Georgina L.
Published: January 2023

Background

Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS.

Aim

We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS.

Methods

Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored.

Results

Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22–75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%).

Conclusion

The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.
Emergency medical service utilization and timely treatment among acute ischemic stroke patients in Beijing from 2018 to 2021
Authors: Ding Kexin , Chen Hui , Wang Yong , Liu Hongmei , Zhang Wenzhong , Wu Yiqun
Published: January 2023

Background and importance

Activation of emergency medical services (EMS) is recommended for timely reperfusion therapy for acute ischemic stroke (AIS). The association of EMS utilization and time intervals from hospital arrival to a series of necessary procedures before reperfusion therapy was rarely investigated.

Objective

The objective of this study is to investigate the association of EMS utilization with the time intervals from hospital arrival to therapy in patients with AIS.

Design

Observational study.

Settings and participants

Medical records for AIS in all emergency departments in Beijing were obtained from January 2018 to December 2021.

Intervention or exposure

Patients transported by ambulance were defined as the EMS group, whereas others as the non-EMS group.

Outcome measures and analysis

Door-to-imaging time (DIT), door-to-needle time (DTN) and door-to-puncture time (DTP) were compared between the two groups.

Main results

There were 11 190 (46%) and 13 106 (54%) AIS patients in the EMS and non-EMS groups. Compared with the non-EMS group, patients in the EMS group were more likely to receive intravenous thrombolysis or endovascular therapy (OR, 1.81; 95% CI, 1.68–1.94). For intravenous thrombolysis therapy, the DIT, ITN (time in minutes from obtaining the first brain imaging to tPA delivery) and DTN times in the EMS group were significantly shorter with time differences between the two groups of −1.1 (95% CI, −1.1 to −1.1) min, −2.6 (−2.6 to −2.6) min, and −3.7 (−3.8, −3.7) min, respectively. The proportion of DIT ≤25 min, DTN ≤45 min or DTN ≤60 min was significantly higher in the EMS group (OR, 1.03, 95% CI, 1.02–1.05; 1.11, 1.07–1.14; 1.05, 1.03–1.07). For endovascular therapy, the differences in DIT, ITP (time in minutes from obtaining the first brain imaging to groin puncture) and DTP times between the EMS and non-EMS groups were +1.1 (1.0–1.2) min, −3.8 (−4.2 to −3.5) min, −2.7 (−3.1 to −2.4) min, respectively, but no significant association was observed between EMS usage and the proportion of DIT ≤25 min or DTP ≤90 min.

Conclusion

In this observational study, the use of EMS for patient with AIS was associated with a shorter time from hospital arrival to intravenous thrombolysis and endovascular therapy.
Nutrition Content of Young Child Formulas
Authors: Du Nan , DiMaggio Dina M. , Porto Anthony F.
Published: January 2023

Objective:

European Society for Pediatric Gastroenterology, Hepatology and Nutrition and the American Academy of Pediatrics state that young child formula (YCF) is not considered necessary for healthy children. Despite these recommendations, YCF accounts for approximately 13% of overall formula sales. Five percent of infants less than 1 year of age in the United States are being fed YCF. The purpose of this study is to identify the most Internet recommended and encountered YCF in the United States and determine if they meet nutritional recommendations for use in children 0–3 years.

Study Design:

We used the search terms “toddler formula,” “toddler milk,” “follow-up formula,” or “young child formula” in Google and DuckDuckGo to identify the most like encountered or recommended YCF on the Internet. We compared their labeled nutrients to Food and Drug Administration (FDA) Infant Formula Act (IFA) and international nutrient recommendations, given the absence of US nutrient requirements for YCF recommendations, for children 12–36 months.

Results:

Twenty-nine YCF were reviewed. On average, YCF did not meet nutrient recommendations for infants and toddlers with 2.17 and 4.6 ingredients not meeting formula recommendations for younger and older infants, respectively, and between 3 and 4 ingredients for 12–36 months.

Conclusions:

Nutrition content of YCF are variable and do not meet FDA IFA requirements or YCF international recommendations. Increased US regulation is needed for YCF. It is important for health care providers to ask patients what they are feeding their infants and toddlers so they can educate parents on potential nutritional safety concerns.
Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients
Authors: Conover Katie R. , Absah Imad , Ballal Sonia , Brumbaugh David , Cho Stanley , Cardenas Maria C. , Knackstedt Elizabeth Doby , Goyal Alka , Jensen M. Kyle , Kaplan Jess L. , Kellermayer Richard , Kociolek Larry K. , Michail Sonia , Oliva-Hemker Maria , Reed Anna W. , Weatherly Madison , Kahn Stacy A. , Nicholson Maribeth R.
Published: January 2023

Objectives:

We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.

Methods:

This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.

Results:

Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered.

Conclusions:

The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.
Factors Associated With Chronic Intestinal Inflammation Resembling Inflammatory Bowel Disease in Pediatric Intestinal Failure: A Matched Case-Control Study
Authors: Culbreath Katherine , Keefe Gregory , Nes Emily , Staffa Steven J. , Carey Alexandra N. , Jaksic Tom , Goldsmith Jeffrey D. , Modi Biren P. , Ouahed Jodie D. , Jimenez Lissette
Published: January 2023

Background and Aims:

There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure.

Methods:

This was a single-center retrospective case-control study of children <18 years old with intestinal failure. Cases were defined by abnormal amounts of chronic intestinal inflammation on biopsies. Children with diversion colitis, eosinophilic colitis, or isolated anastomotic ulceration were excluded. Cases were matched 1:2 to intestinal failure controls based on sex, etiology of intestinal failure, and duration of intestinal failure. Multivariable conditional logistic regression was used to compare clinical factors between cases and controls, accounting for clustering within matched sets. A subgroup analysis was performed assessing factors associated with escalation of anti-inflammatory therapy.

Results:

Thirty cases were identified and matched to 60 controls. On univariate analysis, longer parenteral nutrition (PN) duration (1677 vs 834 days, P = 0.03), current PN use (33.3% vs 20.0%, P = 0.037), and culture-proven bacterial overgrowth (53.3% vs 31.7%, P = 0.05) were associated with chronic intestinal inflammation. On multivariable analysis, no variable reached statistical significance. On subgroup analysis, duration of intestinal failure, location of inflammation, and worst degree of inflammation on histology were associated with escalation of therapy.

Conclusions:

PN dependence and intestinal dysbiosis are associated with chronic intestinal inflammation in children with intestinal failure. Severity of inflammation is associated with escalation of therapy. Further analysis is needed to assess these associations and the efficacy of treatments in this population.
An Effective Combination Therapy for the Treatment of Pediatric Monomorphic Post-transplant Lymphoproliferative Disorder With Plasmacytic Differentiation
Authors: Dumbrava Mihai , Galardy Paul , Feldman Andrew L. , Kuhn Alexis , Khan Shakila , Ferdjallah Asmaa , Kohorst Mira A.
Published: January 2023

Post-transplant lymphoproliferative disorder (PTLD) is a complication of immunosuppressive therapy following solid organ or hematopoietic cell transplantation. Initial treatment typically includes a reduction of immunosuppression with or without rituximab. However, the optimal therapy for PTLD with plasmacytic differentiation is unclear. We present 3 cases of pediatric patients with plasmacytic PTLD. Two patients received a standard rituximab-based approach and relapsed, prompting additional chemotherapy. The third patient was treated with a novel regimen of bortezomib, dexamethasone, and daratumumab. This regimen was safe, well-tolerated, and resulted in a 2-year remission. Larger studies are needed to further explore this regimen.
Short treatment duration for community-acquired pneumonia
Authors: Dinh Aurélien , Crémieux Anne-Claude , Guillemot Didier
Published: January 2023

Purpose of review

Lower respiratory tract infections are one of the most common indications for antibiotic use in community and hospital settings. Usual guidelines for adults with community-acquired pneumonia (CAP) recommend 5–7 days of antibiotic treatment. In daily practice, physicians often prescribe 9–10 days of antibiotic treatment. Among available strategies to decrease antibiotic use, possibly preventing the emergence of bacterial resistance, reducing treatment durations is the safest and the most acceptable to clinicians. We aim to review data evaluating the efficacy of short antibiotic duration in adult CAP and which criteria can help clinicians to reduce antibiotic treatment.

Recent findings

Several studies and meta-analyses demonstrated that the treatment duration of 7 days or less was sufficient for CAP. Two trials found that 3-day treatments were effective, even in hospitalized CAP.

To customize and shorten duration, clinical and biological criteria have been studied and reflect patient's response. Indeed, stability criteria were recently shown to be effective to discontinue antibiotic treatment. Procalcitonin was also studied but never compared with clinical criteria.

Treatment duration for CAP is still under debate, but several studies support short durations. Clinical criteria could be possibly used to discontinue antibiotic treatment.
EARLY PREDICTIVE VALUE OF PRESEPSIN FOR SECONDARY SEPSIS AND MORTALITY IN INTENSIVE CARE UNIT PATIENTS WITH SEVERE ACUTE PANCREATITIS
Authors: Wang Chuanjiang , Zhang Jun , Liu Liyao , Qin Weisheng , Luo Na
Published: January 2023

Purpose: Sepsis is the leading cause of death in patients with severe acute pancreatitis (SAP) in the intensive care unit (ICU). Early prediction of sepsis secondary to SAP developed in the late phase and of related mortality can enable appropriate treatment and improve outcomes. This study was conducted to evaluate the predictive value of presepsin in ICU patients with SAP at the early stage and compared it with established blood markers and scoring systems. Methods: This retrospective study enrolled 48 septic patients and 53 nonseptic patients admitted to ICU with SAP. Presepsin and other blood markers (procalcitonin, C-reactive protein, IL-6, white blood cell, and serum creatinine) on days 1, 3, and 7 after enrollment as well as scoring systems were assessed to predict secondary sepsis. Outcomes were evaluated at ICU discharge and on days 28 and 90. Results: Presepsin levels (on days 1, 3, and 7) were significantly higher in septic patients than in nonseptic patients. Presepsin levels showed an increasing trend over time in both sepsis and nonsepsis groups, but concentrations increased more rapidly in the sepsis group than in the nonsepsis group. Among the analyzed biomarkers, presepsin was the only blood marker independently associated with sepsis secondary to SAP on days 3 and 7, and presepsin on day 3 was independently associated with mortality at ICU discharge and on days 28 and 90. It showed similar or even better predictive accuracy for both secondary sepsis and mortality than procalcitonin and Sequential Organ Failure Assessment score. Conclusion: Presepsin could be a valuable early predictor of secondary sepsis and mortality in patients admitted to the ICU with SAP and may serve as an indicator for early risk stratification.
Filial imprinting in domestic chicks; cytoplasmic polyadenylation element binding protein 3, predispositions and learning
Authors: Chitadze Lela , Tevdoradze Ekaterine , Kiguradze Tamar , McCabe Brian J. , Solomonia Revaz
Published: January 2023

Visual imprinting is a learning process, whereby young animals come to prefer a visual stimulus after exposure to it (training). Available evidence indicates that the intermediate medial mesopallium (IMM) in the domestic chick forebrain is a site of memory formation during visual imprinting. We have found previously that cytoplasmic polyadenylation element binding protein 3 in the P2 plasma membrane-mitochondrial fraction (CPEB3-P2) is upregulated in a learning-dependent way in the left IMM 24 h after training. CPEB3 has two forms, soluble and aggregated. Soluble CPEB3 represses translation; the aggregated form (CPEB3-AF) is amyloid-like and can promote translation. Our previous study did not show which of these two forms is increased after imprinting. We have now resolved this matter by measuring, 24 h after training, CPEB3-P2 and CPEB3-AF in the IMM and a control brain region, the posterior pole of nidopallium (PPN). The methods include imprinting training with a visual stimulus, behavioral measurement of preference, preparation of aggregated CPEB3, western immunoblotting, quantitation of proteins, statistical linear modeling. Only in the left IMM were the level of CPEB3-AF and learning strength correlated, increased CPEB3-AF level reflecting a predisposition to learn readily. CPEB3-P2 level also increased with learning strength in the left IMM, but as a result of learning. No correlations were detected in the right IMM or PPN. We propose two separate systems, both modulating synaptic strength through control of local translation. They are represented by CPEB3-AF (associated with a predisposition to learn) and soluble CPEB3 (associated with learning itself).
Effect of neurotropin on Alzheimer’s disease-like changes and cognitive function in rats with chronic cerebral hypoperfusion
Authors: Ye Ling-ling , Huang Yuan-lu , Cheng Xiao-e , Shi Yin-qi , Liu Zi-ye , Xiong Ying-fen
Published: January 2023

Chronic cerebral hypoperfusion (CCH) is a main mechanism of cerebrovascular disease and is associated with various cerebrovascular and neurodegenerative diseases, including Alzheimer’s disease. However, treatment of CCH in clinical practice is not ideal, but neurotropin (NTP) has been shown to have a neuroprotective effect. Therefore, this study examined the effect and possible mechanism of NTP in nerve injury caused by CCH. A rat CCH model was established by bilateral common carotid artery occlusion (2VO), and rats were treated with intragastric administration of NTP (200 nu/kg/day) for 28 consecutive days. After treatment, rats were subjected to the Morris water maze and novel object recognition test. Subsequently, an ELISA was applied to detect amyloid-β (Aβ) 1–40 and Aβ1–42 levels in rat hippocampal tissues, quantitative reverse transcription PCR assays were used to detect the mRNA expression levels of brain-derived neurotrophic factor (BDNF) and Trk B, and Western blots were used to detect the protein expression levels of BACE1, tau, p-tau, and protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway-related proteins. The rat model of CCH was successfully established by 2VO. Behavioral tests indicated that the cognitive ability of 2VO rats was severely impaired. NTP treatment greatly ameliorated the cognitive disability, reduced Aβ1–40 and Aβ1–42 levels and tau phosphorylation, and upregulated BACE1, Trk B, and BDNF expression in the hippocampus of 2VO rats. Finally, we found that NTP markedly activated Akt/GSK3β pathway activity. NTP can ameliorate cognitive disability in CCH rats possibly by reducing Aβ accumulation and tau phosphorylation in the hippocampus. These effects of NTP may be related to the Akt/GSK3β pathway activation. NTP may be a promising new drug candidate for CCH patients.
Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice
Authors: Malta Iago , Netto Gonçalves , dos Santos Rafaela , Veras Flávio , Galdino Giovane
Published: January 2023

Objectives

Pain is the most common cause of seeking healthcare and the leading cause of disability worldwide. Although cannabidiol and transcutaneous electrical nerve stimulation (TENS) are effective and safe strategies for treating chronic pain, the combined effect of these interventions remains overlooked. To compare the isolated and combined effect of cannabidiol and TENS in the treatment of experimental neuropathic and inflammatory pain.

Methods

Swiss mice were subjected to chronic constriction injury (CCI)-induced neuropathic or carrageenan-induced inflammatory pain models. Cannabidiol or TENS alone and the combination of these therapies were administered once. The nociceptive threshold was measured by the von Frey test. IL-1β, TNF-α and IL-10 cytokine levels were measured by ELISA from spinal cord samples.

Results

Combined, cannabidiol and TENS potentiate antinociception only in neuropathic pain. IL-1β and TNF-α levels were similarly reduced when TENS or cannabidiol were administered alone or in combination. However, only cannabidiol and TENS combined increased IL-10 levels.

Conclusions

Our findings indicated TENS and cannabidiol combined were effective in potentiating antinociception in a neuropathic pain model, an effect potentially associated with spinal IL-10 upregulation.
An investigation into the association between suicide mortality rate and lithium levels in potable water: a review study
Authors: Fadaei Abdolmajid
Published: January 2023

This study aimed to investigate the association between lithium levels in potable water and suicide mortality rates in the total inhabitants. We systematically searched Embase, PubMed/MEDLINE, Scopus, PubMed Central (PMC), Google Scholar databases, as well as medRxiv using the following keywords: drinking water, lithium, standardized mortality ratio (SMR), tap water, suicide, and ground water. Pearson regression analysis was used to test an association between variables with 95% confidence interval (CI). A value of P < 0.05 was considered significant. A total of 16 eligible articles were identified. Lithium concentrations in drinking water range from 0.4 to 32.9 μg/l. Average rates of suicide mortality (per 100 000 capita) range between 0.790 (±0.198) and 123 (±50). About 16 original studies confirmed the inverse relationship between lithium concentrations in potable water and suicide mortality rates (R = −0.576; R
2 = 0.3323; 95% CI, −0.820 to −0.325; β = −0.3.2; P = 0.019). High lithium concentrations in potable water were associated with decreased suicide rates. We concluded that lithium concentration in potable water was inversely associated with suicide mortality rates among a total population. However, further research is required to clarify the relationship between lithium concentrations in drinking water and suicide rate.
Caecal dysfunction in the NL3R451Cmouse model of autism
Authors: Qin Lee Chalystha Yie , Balasuriya Gayathri K. , Herath Madushani , Franks Ashley E. , Hill-Yardin Elisa L.
Published: January 2023

The mouse caecum is a pouch-like structure that is anatomically similar to the human appendix and is hypothesised to serve as a reservoir for commensal bacteria. The gastrointestinal tract is also home to the largest immunological organ of the body and the enteric nervous system (ENS), which regulates gut motility and secretion. The caecum is therefore an ideal location to study neuro-immune-microbe interactions in gut-brain communication. Individuals with Autism Spectrum Disorder (ASD; autism) frequently present with gastrointestinal symptoms in addition to core diagnostic behavioural features, implying a gut-brain link. More broadly, changes in gut-brain connectivity are now thought to play a critical role in a range of neurodevelopmental disorders. Here, we employed a mouse model of autism expressing a missense mutation in the neuroligin-3 post-synaptic protein that affects brain and enteric neuronal activity (NL3R451Cmice). We previously observed abnormal caecal ENS architecture and immune cell morphology in the caecal patch in this model, however it is unknown if caecal function is altered in NL3R451Cmice. Using a tri-cannulation approach to record motility patterns in the mouse caecum, we identified novel caecal motor complexes inex vivopreparations. Caecal permeability and neurally-evoked secretion levels were also studied. Key immune populations including gut macrophages and dendritic cells within the caecal patch were stained using immunofluorescence to investigate shifts in immune activity. Caecal motility patterns in NL3R451Cmice differed from wildtype littermates. Specifically, caecal motor complexes occurred at a higher frequency and for a shorter duration in NL3R451Cmice than in wildtype littermates. In NL3R451Cmice, neurally-evoked caecal secretion was reduced in response to the nicotinic acetylcholine receptor agonist (DMPP), but permeability was unchanged. Increased numbers of caecal patches were observed in NL3R451Cmice compared to wildtype, with no alterations in morphology of selected immune populations. Future research is warranted to better understand caecal function and how neuro-immune interactions in the caecum affect health and influence GI function in neurodevelopmental disorders via the gut-brain axis.
Flushing water regularly inadequate to protect water quality in gravity-fed water supply systems with storage tanks during long-term lockdown
Authors: Bhaskar Deepika , Singh Gargi
Published: January 2023

Flushing of water is recommended to prevent the growth of opportunistic pathogens, corrosion, and deterioration of the water supply network during short-term lockdowns. However, the efficacy of flushing fixtures in water supply networks with intermittent gravity-fed supply during long-term lockdowns is unknown. A laboratory-scale premise water supply network with a secondary storage tank connected to a gravity-fed drinking water distribution network was operated for 52 weeks to compare the efficacy of flushing water once a day (1D) vs. once in three days (3D) to preserve water quality. The tap water sampled from buildings (building) and overhead tanks (OHTs) prior to the pandemic served as a benchmark for comparison. The water quality trended as 1D = 3D < building < OHTs, with both the 1D and 3D yielding ‘poor’ quality water. The water in 3D had higher levels of 16S rRNA gene copies,sul1, andintI1 relative to 1D; this difference was more pronounced (2-3 orders of magnitude) during summer. The levels ofsul1,intI1, and DNA marker ofLegionella pneumophilain biofilms sampled at the end of the operation of the laboratory-scale premise water supply network trended as elbows > visibly corroded pipes-sections > taps. The levels of heavy metals in some tap water samples exceeded the WHO recommendations and BIS standards for drinking water: 32% of 1D samples (30/93), and 31% of 3D samples (29/93) exceeded the standards for Pb, (10 ppb); while 48% (45/93) of 1D samples and 35% (33/93) of 3D samples exceeded the standards for Fe in drinking water (300 ppb).
The Effects of Expectations and Worries on the Experience of COVID-19 Symptoms
Authors: Akintola Titilola , Chung Joyce , Atlas Lauren
Published: January 2023

Introduction

The COVID-19 pandemic has been shown to have profound effects on both mental and physical health. Distress and widespread uncertainty about global events and personal risk are associated with increased worry and negative expectations that impact physical health. Thus, the current pandemic poses a possibility for the experience of nocebo effects.

Objective

To evaluate the likelihood of nocebo-induced COVID-19 symptoms in a US sample.

Methods

An online study on the mental health impact of COVID-19 asked participants to complete a set of biweekly surveys over a 6-month period between April 2020 and May 2021. We focus on responses from 3,027 individuals who reported never testing positive for COVID-19. We assessed the association between two types of worry and self-reported symptoms of COVID-19. We used multi-level models to examine variations across and within participants over time. We further investigated the effects of pre-existing health conditions and mental health status.

Results

There was a positive association between symptoms and both general (b= 2.56, p<0.01) and personal worry (b=2.77, p<0.01). However, worry reported at one timepoint was not specifically associated with symptoms reported two weeks later (p = 0.63, p=0.56). We also found that a greater number of prior clinical comorbidities and greater mental health burden were significant predictors of symptom reporting.

Conclusions

These results suggest that increased worries during the COVID-19 pandemic were associated with greater symptoms. Further studies investigating worry and symptoms in populations with confirmed negative COVID-19 tests or isolated populations will be needed to isolate the occurrence of true nocebo effects during the pandemic.
Traces of pubertal brain development and health revealed through domain adapted brain network fusion
Authors: Kraft Dominik , Alnæs Dag , Kaufmann Tobias
Published: January 2023

Puberty demarks a period of profound brain dynamics that orchestrates changes to a multitude of neuroimaging-derived phenotypes. This poses a dimensionality problem when attempting to chart an individual’s brain development on a single scale. Here, we illustrate shifts in subject similarity of imaging data that relate to pubertal maturation and altered mental health, suggesting that dimensional reference spaces of subject similarity render useful to chart brain dynamics in youths.
An algorithm to identify patients with rare genetic disorders and its real-world data application
Authors: Webb Bryn D. , Lau Lisa Y. , Tsevdos Despina , Shewcraft Ryan A. , Corrigan David , Shi Lisong , Lee Seungwoo , Tyler Jonathan , Li Shilong , Wang Zichen , Stolovitzky Gustavo , Edelmann Lisa , Chen Rong , Schadt Eric E. , Li Li
Published: January 2023

Objectives

Develop a digital phenotyping algorithm (PheIndex) using electronic medical records (EMR) data to identify children aged 0-3 who have been diagnosed with genetic disorders or present with illness with an increased risk for genetic disorders from a mother-child cohort.

Methods

We established 13 criteria for the algorithm where two metrics – a quantified score and a classification – were derived. The criteria and the classification were validated by chart review from a pediatrician and clinical geneticist. To demonstrate the utility of our algorithm in real-world evidence applications, we examined the association between size of carrier screening panel (small/≤4 genes [CS-S] vs large/≥100genes [CS-L]) undertaken by mothers prior to delivery, and children classified as presenting with illness with an increased risk for genetic disorders by our algorithm.

Results

The PheIndex algorithm identified 1,088 such children out of 93,154 live births and achieved 90% sensitivity, 97% specificity, and 94% accuracy by chart review. We found that children whose mothers received CS-L were less likely to be classified as presenting with illness with an increased risk for genetic disorders and a decreased need to have multiple specialist visits and multiple ER visits, compared to children whose mothers received CS-S.

Conclusions

The PheIndex algorithm can help identify when a rare genetic disorder may be present, and has the potential to improve healthcare delivery by alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist or other specialists.

Article Summary

Algorithm using EMR data to identify children who have been diagnosed with a genetic disorder or present with illness with increased risk of genetic disorders.

What’s known on this subject

With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured EMR data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders.

What this study adds

We developed a digital phenotyping algorithm using electronic medical records (EMR) data to identify children aged 0-3 who have been diagnosed with genetic disorders or present with illness with an increased risk for genetic disorders from a mother-child cohort.
Distinct tumor architectures for metastatic colonization of the brain
Authors: Gan Siting , Macalinao Danilo G. , Shahoei Sayyed Hamed , Tian Lin , Jin Xin , Basnet Harihar , Muller James T. , Atri Pranita , Seffar Evan , Chatila Walid , Hadjantonakis Anna-Katerina , Schultz Nikolaus , Brogi Edi , Bale Tejus A. , Pe’er Dana , Massagué Joan
Published: January 2023

Brain metastasis is a dismal cancer complication, hinging on the initial survival and outgrowth of disseminated cancer cells. To understand these crucial early stages of colonization, we investigated two prevalent sources of cerebral relapse, triple-negative (TNBC) and HER2+ breast cancer (HER2BC). We show that these tumor types colonize the brain aggressively, yet with distinct tumor architectures, stromal interfaces, and autocrine growth programs. TNBC forms perivascular sheaths with diffusive contact with astrocytes and microglia. In contrast, HER2BC forms compact spheroids prompted by autonomous extracellular matrix components and segregating stromal cells to their periphery. Single-cell transcriptomic dissection reveals canonical Alzheimer’s disease-associated microglia (DAM) responses. Differential engagement of tumor-DAM signaling through the receptor AXL suggests specific pro-metastatic functions of the tumor architecture in both TNBC perivascular and HER2BC spheroidal colonies. The distinct spatial features of these two highly efficient modes of brain colonization have relevance for leveraging the stroma to treat brain metastasis.
Subcortical correlates of consciousness with human single neuron recordings
Authors: Pereira Michael , Faivre Nathan , Bernasconi Fosco , Brandmeir Nicholas , Suffridge Jacob , Tran Kaylee , Wang Shuo , Finomore Victor , Konrad Peter , Rezai Ali , Blanke Olaf
Published: January 2023

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness is still unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing rate of 23% of these neurons differed between detected and undetected stimuli. Our results provide direct neurophysiological evidence of the involvement of the subthalamic nucleus and the thalamus for the detection of vibrotactile stimuli, thereby calling for a less cortico-centric view of the neural correlates of consciousness.
Can a fish learn to ride a bicycle? Sensorimotor adaptation to destabilizing dynamics in the weakly electric fishEigenmannia virescens
Authors: Yang Yu , Yared Dominic G. , Cowan Noah J.
Published: January 2023

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Humans and other animals can readily learn to compensate for destabilizing dynamics, such as balancing an object or riding a bicycle. How does the nervous system learn to compensate for such destabilizing dynamics, and what are the benefits of the newly learned control policies? To investigate these questions, we examined how the weakly electric glass knifefish,Eigenmannia virescens, retunes its control system in the face of novel, destabilizing dynamics. Using a real-time feedback system, we measured swimming movements as seven individual fish tracked a moving refuge, and we fed the swimming movements back through novel dynamics to alter the refuge motion, creating an artificially destabilizing reafferent loop. We discovered that fish learned to retune their sensorimotor controllers as the artificially destabilizing feedback was gradually introduced. Furthermore, when the artificial feedback was extinguished, fish exhibited a clear aftereffect, retaining their learned sensorimotor controllers for several minutes before washing out. This retuning of the control system under destabilizing dynamics: (i) improved tracking performance compared to the predicted performance had fish not re-tuned their baseline controller, (ii) reduced sensitivity of the sensorimotor system to low-frequency disturbances, such as would arise from turbulence or motor noise, and (iii) improved phase margin, a measure of stability robustness, despite the artificial feedback driving the putative baseline control system towards instability. Our study sheds light on how the nervous system adapts to changing closed-loop dynamics, and how those changes impact performance and stability; the presence of aftereffects suggest a plasticity-based mechanism reminiscent of cerebellar learning.
Intralimb locomotor coordination in rats walking on asymmetric pegway
Authors: Hanna Kacie , Salido Ezequiel M , Lal Neha , Tuntevski Kiril , Yakovenko Sergiy
Published: January 2023

Complex movements such as walking or reaching are generated by a sequence of muscle actions. How these coordinated actions subserve complex movements and their recovery after disruption remains unknown. The use of high throughput recording-stimulation systems with microelectrode access to structures along the neuraxis may complement the neurological models in rodents. To this purpose, we have trained rats to perform the precise foot placement locomotor task that allows us to assess skilled locomotor movements. Animals were pretrained on the peg walkway task, which was configured to impose either symmetric or asymmetric (with overstepping) locomotor stepping at preferred stride length. Selected forelimb muscles were implanted with intramuscular differential electrodes. After a week of recovery, we collected electromyography from the implanted muscles and ground reaction forces from the array of force sensors embedded into walkway pegs. The temporal relationship between muscle bursts was measured for each intralimb set of muscles (n=13) in symmetric and asymmetric stepping. The sequence corresponded to the progression of muscle actions responsible for limb lift, flexion and transport, overground clearance, and preparation for ground contact. The stereotyped spatiotemporal sequence of muscle activity was persistent and mirroring across the asymmetric tasks. These patterns are similar to those observed in cats during locomotion with and without obstacles and reaching movements. These findings support the hypothesis that the profiles of muscle activations are qualitatively similar across quadrupeds during precise locomotor tasks.

New and Noteworthy

We characterize for the first time the spatiotemporal muscle activation in rat forelimb during precise asymmetric stepping on asymmetrically placed rungs. Similar to cats, the intralimb pattern of muscle activation in rats was stereotypical. The elements of this pattern were changing in a lateralized fashion based on the direction of the imposed asymmetry. The similarity of pattern to that of cats supports the idea of similarity of neural control across cat and rat species.
Characterization and decontamination of background noise in droplet-based single-cell protein expression data with DecontPro
Authors: Yin Yuan , Yajima Masanao , Campbell Joshua D.
Published: January 2023

Assays such as CITE-seq can measure the abundance of cell surface proteins on individual cells using antibody derived tags (ADTs). However, many ADTs have high levels of background noise that can obfuscate down-stream analyses. Using an exploratory analysis of PBMC datasets, we find that some droplets that were originally called “empty” due to low levels of RNA contained high levels of ADTs and likely corresponded to neutrophils. We identified a novel type of artifact in the empty droplets called a “spongelet” which has medium levels of ADT expression and is distinct from ambient noise. ADT expression levels in the spongelets correlate to ADT expression levels in the background peak of true cells in several datasets suggesting that they can contribute to background noise along with ambient ADTs. We then developed DecontPro, a novel Bayesian hierarchical model that can decontaminate ADT data by estimating and removing contamination from these sources. DecontPro outperforms other decontamination tools in removing aberrantly expressed ADTs while retaining native ADTs and in improving clustering specificity. Overall, these results suggest that identification of empty drops should be performed separately for RNA and ADT data and that DecontPro can be incorporated into CITE-seq workflows to improve the quality of downstream analyses.
Multifunctional ferromagnetic fiber robots for navigation, sensing, and treatment in minimally invasive surgery
Authors: Zhang Yujing , Wu Xiaobo , Vadlamani Ram Anand , Lim Youngmin , Kim Jongwoon , David Kailee , Gilbert Earl , Li You , Wang Ruixuan , Jiang Shan , Wang Anbo , Sontheimer Harald , English Daniel , Emori Satoru , Davalos Rafael V. , Poelzing Steven , Jia Xiaoting
Published: January 2023

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Here, we present a robotic fiber platform for integrating navigation, sensing, and therapeutic functions at a submillimeter scale. These fiber robots consist of ferromagnetic, electrical, optical, and microfluidic components, fabricated with a thermal drawing process. Under magnetic actuation, they can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, we utilize Langendorff mouse hearts model, glioblastoma microplatforms, and in vivo mouse models to demonstrate the capabilities of sensing electrophysiology signals and performing localized treatment. Additionally, we demonstrate that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.
lydemapr: an R package to track the spread of the invasive Spotted Lanternfly (Lycorma delicatula, White 1845) (Hemiptera, Fulgoridae) in the United States
Authors: De Bona Sebastiano , Barringer Lawrence , Kurtz Paul , Losiewicz Jay , Parra Gregory R. , Helmus Matthew R.
Published: January 2023

A crucial asset in the management of invasive species is the open-access sharing of data on the range of invaders and the progression of their spread. Such data should be current, comprehensive, consistent, and standardized, to support reproducible and comparable forecasting efforts among multiple researchers and managers. Here, we present thelydemaprR package containing spatiotemporal data and mapping functions to visualize the current spread of the spotted lanternfly (Lycorma delicatula, White 1841) in the Western Hemisphere. The spotted lanternfly is a forest and agricultural pest in the eastern Mid-Atlantic region of the U.S., where it was first discovered in 2014. As of 2022, it has been found in 12 states according to state and federal departments of agriculture. However, the lack of easily accessible, fine-scale data on its spread hampers research and management efforts. We obtained multiple memoranda-of-understanding from several agencies and citizen-science projects, gaining access to their internal data on spotted lanternfly point observations. We then cleaned, harmonized, anonymized, and combined the individual data sources into a single comprehensive dataset. The resulting dataset contains spatial data gridded at the 1 km2resolution, with yearly information on the presence/absence of spotted lanternflies, establishment status, and population density across 658,392 observations. Thelydemaprpackage will aid researchers, managers, and the public in their understanding, modeling, and managing of the spread of this invasive pest.
Altered transcriptomes, cell type proportions, and dendritic spine morphology in hippocampus of suicide deaths
Authors: Das Sujan C. , Schulmann Anton , Callor William B. , Jerominski Leslie , Panicker Mitradas M. , Christensen Erik D. , Bunney William E. , Williams Megan E. , Coon Hilary , Vawter Marquis P.
Published: January 2023

Suicide is a condition resulting from complex environmental and genetic risks that affect millions of people globally. Both structural and functional studies identified the hippocampus as one of the vulnerable brain regions contributing to suicide risk. Here, we have identified the hippocampal transcriptomes, gene ontology, cell type proportions, dendritic spine morphology, and transcriptomic signature in iPSC-derived neuronal precursor cells (NPCs) and neurons in postmortem brain tissue from suicide deaths. The hippocampal tissue transcriptomic data revealed thatNPAS4gene expression was downregulated whileALDH1A2, NAAA, andMLXIPLgene expressions were upregulated in tissue from suicide deaths. The gene ontology identified 29 significant pathways includingNPAS4-associated gene ontology terms “excitatory post-synaptic potential”, “regulation of postsynaptic membrane potential” and “long-term memory” indicating alteration of glutamatergic synapses in the hippocampus of suicide deaths. The cell type deconvolution identified decreased excitatory neuron proportion and an increased inhibitory neuron proportion providing evidence of excitation/inhibition imbalance in the hippocampus of suicide deaths. In addition, suicide deaths had increased dendric spine density, due to an increase of thin (relatively unstable) dendritic spines, compared to controls. The transcriptomes of iPSC-derived hippocampal-like NPCs and neurons revealed 31 and 33 differentially expressed genes in NPC and neurons, respectively, of suicide deaths. The suicide-associated differentially expressed genes in NPCs wereRELN, CRH, EMX2, OXTR, PARM1andIFITM2which overlapped with previously published results. The previously-known suicide-associated differentially expressed genes in differentiated neurons wereCOL1A1, THBS1, IFITM2, AQP1, andNLRP2. Together, these findings would help better understand the hippocampal neurobiology of suicide for identifying therapeutic targets to prevent suicide.
Modified Robust Meta-Analytic-Predictive Priors for Incorporating Historical Controls in Clinical Trials
Authors: Zhao Qiang , Ma Haijun
Published: January 2023

Incorporating historical information in clinical trials has been of much interest recently because of its potential to reduce the size and cost of clinical trials. Data-conflict is one of the biggest challenges in incorporating historical information. In order to address the conflict between historical data and current data, several methods have been proposed including the robust meta-analytic-predictive (rMAP) prior method. In this paper, we propose to modify the rMAP prior method by using an empirical Bayes approach to estimate the weights for the two components of the rMAP prior. Via numerical calculations, we show that this modification to the rMAP method improves its performance regarding multiple key metrics.