bluuebunny/crossref_metadata_2025 huggingface dataset:
Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection
Authors: Maslennikov Roman , Svistunov Andrey , Ivashkin Vladimir , Ufimtseva Anna , Poluektova Elena , Efremova Irina , Ulyanin Anatoly , Okhlobystin Alexey , Kardasheva Svetlana , Kurbatova Anastasia , Levshina Anna , Grigoriadis Diana , Magomedov Shamil , Dzhakhaya Natiya , Shifrin Oleg , Zharkova Maria , Yuryeva Elena , Kokina Nataliya , Shirtladze Manana , Kiseleva Olga
Published: November 2021

Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea.

We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization.

There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4–10] vs 5 [3–7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 109 cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710–0.872]).

Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.
Analysis on clinical association of uterine scar diverticulum with subsequent infertility in patients underwent cesarean section
Authors: Bi Beilei , Gao Shanshan , Ruan Fan , Shi Yin , Jiang Yi , Liu Songjun , Lv Wen
Published: November 2021

To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.

A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.

Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ± 0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ± 0.90 vs 0.47 ± 0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ± 1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).

Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors.
EMX2OS plays a prognosis-associated enhancer RNA role in gastric cancer
Authors: Liu Ge-Xin , Tan Yu-Zhen , He Guo-Chao , Zhang Qin-Lin , Liu Pan
Published: November 2021

Enhancer RNAs (eRNAs), a subclass of lncRNAs, are derived from enhancer regions. The function of eRNAs has been reported by many previous studies. However, the role of eRNAs in gastric cancer, especially the prognosis-associated eRNAs, has not been studied yet.

In this study, we have used a novel approach to screened key eRNAs in gastric cancer. Kaplan–Meier correlation analysis and Co-expression analysis were used to find the most significant survival-associated eRNAs. Enrichment analysis is applied to explore the key functions and pathways of screened eRNAs. The correlation and survival analysis are used to evaluate targeted genes in the pan-cancer analysis

A total of 63 prognostic-associated eRNAs in gastric cancer were identified, the top 6 eRNAs were LINC01714, ZNF192P1, AC079760.2, LINC01645, EMX2OS, and AC114489.2. The correlation analysis demonstrated the top 10 screened eRNAs and their targeted genes. The results demonstrated that EMX2OS was ranked as the top eRNA according to the results of the Kaplan–Meier analysis. The correlation analysis demonstrated that eRNA EMX2OS is correlated with age, grade, stage, and cancer status. The pan-cancer analysis demonstrated that EMX2OS was associated with poor survival outcomes in adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, stomach adenocarcinoma, and uveal melanoma.

In this study, survival-related eRNAs were screened and the correlation between survival-related eRNAs and their targeted genes was demonstrated. EMX2OS plays a prognosis-associated eRNA role in gastric cancer, which might be a novel therapeutic target in clinical practice.
Prevalence of COVID-19 among blood donors
Authors: Elnasser Ziad , Obeidat Haneen , Amarin Zouhair , Alrabadi Nasr , Jaradat Abdullah , Alomarat Du’a , BaniSalem Mo’ath , Almomani Randa
Published: November 2021

The corona virus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, had health and economic results that profoundly affected communities worldwide. Investigating the seroprevalence of SARS-Cov-2 in blood donors is of a significant clinical and scientific value as it adds to knowledge about local herd immunity levels.

To study the prevalence of SARS-Cov-2 infection among blood donors at a tertiary referral hospital in the north of Jordan.

This is a prospective study that included all blood donors between September 2020 and March 2021. Donors’ IgG antibodies were qualitatively immunoassayed to determine the antibody status against SARS-CoV-2. The Elecsys Anti-SARS-CoV-2 technique was utilized.

One thousand samples were tested by total antibody against SARS-CoV-2. The median age was 29 years, 96.7% were males. The seroprevalence was 14.5%, and 80% of the positive participants did not report previous COVID-19 infection. The seroprevalence of COVID-19 antibodies was less among smokers and those with an O blood group and higher among donors with an AB blood group.

The prevalence of COVID-19 among healthy young blood donors at a tertiary teaching health facility in the north of Jordan was 14.5%. Smokers and those with an O blood group were less likely to be seropositive, as opposed to donors with an AB blood group.
Transrectal povidone-iodine efficiency in reducing infections occurring after transrectal ultrasound guided biopsy of the prostate
Authors: Siyez Ender
Published: November 2021

The present study aimed to compare infectious complications in men undergoing transrectal ultrasound-guided prostate biopsy (TRUS-Bx) with and without povidone-iodine transrectal injection using a gavage syringe.

The records of 112 patients, who underwent TRUS-Bx between January 2016 and December 2019, were retrospectively reviewed. The biopsy indication was considered high prostate-specific antigen (PSA) level and/or suspicious digital rectal prostate examination findings. Patients’ ages, underlying diseases, PSA levels, prostate volumes, pathologic results, and infectious complications after the biopsy were investigated. All the patients received 1500 mg of ciprofloxacin (750 mg twice a day) for 5 days, starting from the day before the procedure. Forty-seven (41.96%) patients received ciprofloxacin prophylaxis with povidone-iodine transrectal injection, while 65 (58.03%) only received ciprofloxacin prophylaxis. All the patients, who were readmitted to the hospital after the procedure, especially with a temperature of higher than 37.8°C, were detected. For the purposes of the study, the priority was placed on the emergence of the rate of febrile infectious complications. Differences in febrile infectious complications in patients, who received ciprofloxacin prophylaxis with transrectal povidone-iodine, and those, who received ciprofloxacin prophylaxis alone before TRUS-Bx, were studied.

Febrile infectious complications developed in 10 cases (15.38%) in patients, who received ciprofloxacin antibiotics prophylaxis alone. In the povidone-iodine rectal disinfection group, there was only 1 case of febrile infectious complication (2%). There was no significant difference by clinicopathologic features, age, PSA level, and cancer detection rate between both groups (P > .05). Multivariate logistic regression analysis did not identify any patient subgroups at a significantly higher risk of infection after prostate biopsy. There was no significant side effect associated with povidone iodine.

In addition to the use of prophylactic antibiotics, transrectal povidone-iodine was useful in reducing the febrile infection complications following TRUS-Bx.
Guidelines for Designing and Evaluating Feasibility Pilot Studies
Authors: Teresi Jeanne A. , Yu Xiaoying , Stewart Anita L. , Hays Ron D.
Published: November 2021

Background:

Pilot studies test the feasibility of methods and procedures to be used in larger-scale studies. Although numerous articles describe guidelines for the conduct of pilot studies, few have included specific feasibility indicators or strategies for evaluating multiple aspects of feasibility. In addition, using pilot studies to estimate effect sizes to plan sample sizes for subsequent randomized controlled trials has been challenged; however, there has been little consensus on alternative strategies.

Methods:

In Section 1, specific indicators (recruitment, retention, intervention fidelity, acceptability, adherence, and engagement) are presented for feasibility assessment of data collection methods and intervention implementation. Section 1 also highlights the importance of examining feasibility when adapting an intervention tested in mainstream populations to a new more diverse group. In Section 2, statistical and design issues are presented, including sample sizes for pilot studies, estimates of minimally important differences, design effects, confidence intervals (CI) and nonparametric statistics. An in-depth treatment of the limits of effect size estimation as well as process variables is presented. Tables showing CI around parameters are provided. With small samples, effect size, completion and adherence rate estimates will have large CI.

Conclusion:

This commentary offers examples of indicators for evaluating feasibility, and of the limits of effect size estimation in pilot studies. As demonstrated, most pilot studies should not be used to estimate effect sizes, provide power calculations for statistical tests or perform exploratory analyses of efficacy. It is hoped that these guidelines will be useful to those planning pilot/feasibility studies before a larger-scale study.
Emerging biomarkers in kidney transplantation and challenge of clinical implementation
Authors: Westphal Scott G. , Mannon Roslyn B.
Published: November 2021

Purpose of review

Despite improvement in short-term outcomes after kidney transplantation, long-term outcomes remain suboptimal. Conventional biomarkers are limited in their ability to reliably identify early immunologic and nonimmunologic injury. Novel biomarkers are needed for noninvasive diagnosis of subclinical injury, prediction of response to treatment, and personalization of the care of kidney transplant recipients.

Recent findings

Recent biotechnological advances have led to the discovery of promising molecular biomarker candidates. However, translating potential biomarkers from bench to clinic is challenging, and many potential biomarkers are abandoned prior to clinical implementation. Despite these challenges, several promising urine, blood, and tissue novel molecular biomarkers have emerged and are approaching incorporation into clinical practice.

This article highlights the challenges in adopting biomarker-driven posttransplant management and reviews several promising emerging novel biomarkers that are approaching clinical implementation.
A Knee Height Equation for Estimating Height of Vietnamese Adults
Authors: Nguyen Tu Huu , Ma Yen Ngoc , Nguyen Linh Thuy
Published: November 2021

Critically ill or immobilized patients are unable to stand for their height to be measured; therefore, knee height measurement is a useful proxy. In order to address this problem, a lot of research has been carried out worldwide to create equations to estimate the stature of adults. However, knee and total height may differ among racial/ethnic groups. This study therefore determined the applicability of equations to estimate stature derived from American and Taiwanese research and then established a new equation from a group of 512 Vietnamese patients aged 18 to 64 years. In this study, 512 patients were divided into 2 groups, the established equation group (n = 400, 214 men and 186 women) and the validated equation group (n = 112, 61 men and 51 women). Based on the linear regression model, the new equation is: body height = 2.12 × knee height + 59.06 (cm) in males and body height = 2.09 × knee height + 57.37 (cm) in females. We calculated the heights of patients based on their knee heights with both equations and then compared the results with their measured standing heights. The results from the American and Taiwanese knee height equations both showed that the difference was statistically significant with a P < .05 between the indirect method of stature estimation with actual body height. In contrast, the new equation was more accurate with a P > .05. Stature estimated from the new knee height equation is suitable for the Vietnamese population in clinical setting.
Finding value with prehabilitation in older persons receiving surgery
Authors: Ng Priscilla , Lee Jin Keat Daniel , Tan Kok Yang
Published: November 2021

Purpose of review

Patients presenting for surgery are increasingly older and frail. Prehabilitation offers the best hope of preemptive functional optimisation to improve postoperative outcomes. Systematic reviews and meta-analyses show signals of improved function and reduced complications and length of stay, but are hampered by small trials with heterogeneous nature of interventions.

Recent findings

The value proposition for prehabilitation is strengthened by applying the following considerations to the evidence. Multimodal prehabilitation programmes incorporating elements of exercise, nutrition, and psychological preparation have a sound physiological basis and will help standardise care delivery and evidence gathering. Targeting prehabilitation resources at high-risk patients may yield higher returns. Effective prehabilitation programmes must be individualised and pragmatic to address known barriers to adherence. The evidence for functional improvement is clear and this aligns with the values of older patients. A comprehensive analysis of value incorporates functional, quality of life, and cost outcomes in addition to conventional morbidity and mortality measures.

Multimodal prehabilitation delivered by a multidisciplinary team improves functional outcomes following surgery. Function is an integral part of multidimensional value assessment including clinical and experiential measures. Future value enhancements include addressing frailty and overcoming barriers through targeted programme design.
Cerebrovascular disease in pregnancy and postpartum
Authors: Santos Mónica , de Sousa Diana Aguiar
Published: November 2021

Purpose of review

Cerebrovascular disorders during pregnancy and puerperium are uncommon but potentially serious entities. This review aims to provide guidance on the diagnosis and management of these diseases, according to the most recent findings.

Recent findings

Proteinuria is no longer a mandatory criterion for the diagnosis of preeclampsia. Favourable long-term foetal and maternal outcomes are achieved in most patients with ruptured cerebral arterial malformations during pregnancy receiving interventional treatment prior to delivery. Despite the recent recommendations, physicians still hesitate to administer thrombolysis in pregnant women. In women with a history of cerebral venous thrombosis, prophylaxis with low molecular weight heparin during pregnancy and puerperium is associated with lower rates of recurrent thrombotic events and miscarriage.

Hypertensive disorders of pregnancy are a continuum of failure of autoregulation mechanisms that may lead to eclampsia, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome and stroke. MRI is the preferred imaging modality of choice. In the absence of specific contraindications, treatment of cerebrovascular complications should not be withheld from pregnant women, including reperfusion therapies in acute ischemic stroke and treatment of ruptured cerebral aneurysms. Previous history of stroke alone does not contraindicate future pregnancy, but counselling and implementation of prevention strategies are needed.
Implementation of strategies to improve nutritional intervention for patients with cancer treatment-related oral mucositis: a best practice implementation project
Authors: Zhang Lanfang , Zhou Chunlan , He Ling , Wu Yanni , Xie Guozhu , Chen Peijuan
Published: November 2021

Background:

Oral mucositis is a common complication after radiotherapy or chemotherapy in cancer patients. Oral mucositis can affect the patient's food intake and their confidence in treatment as patients are more likely to suffer severe pain, experience weight loss, encounter an interruption or change of cancer treatment plan, and are reported to have a reduced survival from the disease. Nutritional intervention is the primary nursing focus in patients with oral mucositis treated by chemoradiotherapy.

Objectives:

The current best practice implementation project aimed to establish best practice principles in nutritional interventions for patients with cancer treatment-related oral mucositis.

Methods:

This was an evidence-based audit and feedback project that used a three-phase approach at a public hospital in China. Phase 1 involved developing five evidence-based audit criteria informed by current best available evidence, and undertaking a clinical audit of current practice on 50 patients in the Department of Radiation Oncology of Nanfang Hospital using the JBI's Practical Application of Clinical Evidence System. Phase 2 utilized the Getting Research into Practice component of the Practical Application of Clinical Evidence System to identify barriers to compliance with best practice principles and developed strategies and resources to improve compliance. Phase 3 involved conducting a postaudit using the same sample size and audit criteria to re-evaluate compliance with best practice.

Results:

Baseline results showed that compliance rates were 0% for criteria 1 and 2, 76% for criteria 3 and 5, and 82% for criterion 4. The implementation of strategies, including establishing a multidisciplinary team with a dietitian, creating training and education programs for all staff and patients, utilizing a scale regarding diet to assess patients’ current diet, and establishing a nutrition intervention nursing procedure to supervise implementation of the nutritional intervention for patients with cancer treatment-related oral mucositis, increased compliance with best practice, achieving compliance rates of at least 82% for all five audit criteria.

Conclusion:

The implementation of context-specific strategies improved compliance with evidence-based practice in the nutritional intervention for patients with cancer treatment-related oral mucositis. Sustainability of best practice is important, with further audits planned to evaluate the sustainability of these practice changes.
Molecular mechanisms of macrolide and fluoroquinolone resistance among Korean isolates of Mycoplasma genitalium over a period of five years 2014–2019
Authors: Seo Yumi , Park Heeyoon , Lee Gilho
Published: November 2021

Antimicrobial resistance in

Mycoplasma genitalium

has become a global issue, and certain groups have a higher probability of acquiring resistant strains. Little is known about the genetic diversity and characteristics of the antimicrobial resistance-determining sites (ARDSs) of

M. genitalium

in the Korean population. Therefore, we examined the genetic diversity of the ARDSs of M. genitalium-positive urogenital samples obtained from Korean females (G1) and males (G2) visiting primary care clinics and DNA samples from referred males (G3) with persistent urethritis. From 2014 to 2019, 54 patients from G1, 86 patients from G2, and 68 patients from G3 were included in the study. Sanger sequencing was performed on the 2058/2059 sites in the 23S rRNA gene and quinolone resistance-determining regions (QRDRs) of

M. genitalium

. The rates of mutation in G1, G2, and G3 were 1.85, 5.81, and 48.53 %, respectively, for A2059G in the 23S rRNA gene (P<0.001); 1.85, 0, and 17.78 %, respectively, for M95R or I in gyrA (P<0.001); 0, 0, and 31.11 %, respectively, for D99N or G in gyrA (P<0.001); and 7.41, 16.28, and 30 %, respectively, for S83R or N or I in parC (P=0.015). A2059G significantly increased the risk of mutations at the gyrA95, gyrA99, and parC83 sites (all P<0.01). In conclusion, although the genetic diversity of the ARDSs of

M. genitalium

was variable among the groups, it was generally lower in isolates with macrolide resistance and higher in isolates with quinolone resistance in Korea compared with the isolates in other countries. The G3 group demonstrated increased genetic diversity at the A2059G, gyrA95, gyrA99, and parC83 sites.
Gender dysphoria and sexual euphoria – A Bayesian perspective on the influence of gender-affirming hormone therapy on sexual arousal
Authors: Klöbl Manfred , Reed Murray Bruce , Handschuh Patricia , Kaufmann Ulrike , Konadu Melisande Elisabeth , Ritter Vera , Spurny-Dworak Benjamin , Kranz Georg S. , Lanzenberger Rupert , Spies Marie
Published: November 2021

While the concept of sexual orientation is more clearly defined in cisgender, this is less so in transgender individuals. Both experienced gender and sex hormones have a relation to sexual preferences, arousal in response to erotic stimuli, and thus sexual orientation. In transgender individuals sexual orientation occasionally changes before or during transition, which may involve gender-affirming hormone therapy. Using functional magnetic resonance imaging, we investigated whether the neuronal and behavioral patterns of sexual arousal in transgender individuals moved from the given (before) to their chosen gender after 4.5 months of hormone therapy. To this aim, trans women and men as well as age-matched cisgender controls rated visual stimuli showing heterosexual, lesbian or gay intercourse for subjective sexual arousal. Utilizing a Bayesian framework allowed us to incorporate behavioral findings in cisgender individuals of different sexual orientations. The hypothesized changes in response patterns could indeed be observed in the behavioral responses to the single but not the differentiation between stimulus categories with the strongest results for trans men and lesbian scenes. Activation of the ventral striatum supported our hypothesis only for lesbian scenes in trans women. This prominent role of lesbian stimuli might be explained by their differential responses in cis women and men. We show that correlates of sexual arousal in transgender individuals might change in direction of the chosen gender. Future investigations longer into transition might resolve the discrepancy on behavioral and neuronal levels.
Long-term decreased cannabinoid type-1 receptor activity restores specific neurological phenotypes in the Ts65Dn mouse model of Down syndrome
Authors: Vázquez-Oliver Anna , Pérez-García Silvia , Pizarro Nieves , Molina-Porcel Laura , de la Torre Rafael , Maldonado Rafael , Ozaita Andrés
Published: November 2021

Intellectual disability is the most prevalent and limiting hallmark of Down syndrome (DS), without any pharmacological treatment available. Neurodegeneration and neuroinflammation are relevant neurological features of DS reaching to early development of Alzheimer’s disease. Preclinical evidence suggests that the endocannabinoid system, an important neuromodulator on cognition and neuroinflammation, could act as beneficial target in DS. Indeed, cannabinoid type-1 receptor (CB1R) activity was enhanced in the hippocampus of young-adult trisomic Ts65Dn mice, a well-characterized surrogate model of DS. In previous studies, inhibition of CB1R, was able to restore key neurological deficits in this mouse model. To determine the possible clinical relevance of this target, it is mandatory to evaluate the long-term consequences of attenuated CB1R activity and to minimize the possible side-effects associated to this mechanism. We found that CB1R expression was significantly enhanced in the hippocampus brains of aged DS subjects. Similarly, middle-aged trisomic mice showed enhanced CB1R expression. Long-term oral administration of a low dose of the CB1R specific antagonist rimonabant was administered to male and female Ts65Dn trisomic and wild-type mice from the time of weaning to 10 months, an age when signs of neurodegeneration have been described in the model. CB1R inhibition resulted in significant cognitive improvement in novel object-recognition memory in trisomic male and female mice, reaching a similar performance to that of wild-type littermates. Interestingly, this long-term rimonabant treatment modify locomotor activity, anxiety-like behavior, body weight or survival rates. Brain analysis at 10 months of age revealed noradrenergic and cholinergic neurodegeneration signs in trisomic mice that were not modified by the treatment, although the alterations in hippocampal microglia morphology shown by vehicle-treated trisomic mice was normalized in trisomic mice exposed to rimonabant. Altogether, our results demonstrate a sustained pro-cognitive effect of CB1R inhibition at doses that do not produce major side effects that could be associated to an anti-inflammatory action, suggesting a potential interest in this target of to preserve cognitive functionality in DS.
The role of indirect effects in coevolution as mutualism transitions into antagonism
Authors: Pedraza Fernando , Liu Hanlun , Gawecka Klementyna A. , Bascompte Jordi
Published: November 2021

Species interactions have evolved from antagonistic to mutualistic and back several times throughout life’s history. Yet, it is unclear how changes in the type of interaction between species alter the coevolutionary dynamics of entire communities. This is a pressing matter, as transitions from mutualisms to antagonisms may be becoming more common with human-induced global change. Here, we combine network and evolutionary theory to simulate how shifts in interaction types alter the coevolution of empirical communities. We show that as mutualistic networks shift to antagonistic, selection imposed by direct partners begins to outweigh that imposed by indirect partners. This weakening of indirect effects is associated with communities losing their tight integration of traits and increasing their rate of adaptation. The above changes are more pronounced when specialist consumers are the first species to switch to antagonism. A shift in the outcome of species’ interactions may therefore reverberate across communities and alter the direction and speed of coevolution.
Causal contributions of neural noise to left frontal networks subtending the modulation of conscious visual perception in the human brain
Authors: Stengel Chloé , Amengual Julià L. , Moreau Tristan , Valero-Cabré Antoni
Published: November 2021

For several decades, the field of human neurophysiology has focused on the role played by cortical oscillations in enabling brain function underpinning behaviors. In parallel, a less visible but robust body of work on the stochastic resonance phenomenon has also theorized contributions of neural noise − hence more heterogeneous, complex and less predictable activity − in brain coding. The latter notion has received indirect causal support via improvements of visual function during non-regular or random brain stimulation patterns. Nonetheless, direct evidence demonstrating an impact of brain stimulation on direct measures of neural noise is still lacking. Here we evaluated the impact of three non frequency-specific TMS bursts, compared to a control pure high-beta TMS rhythm, delivered to the left FEF during a visual detection task, on the heterogeneity, predictability and complexity of ongoing brain activity recorded with scalp EEG. Our data showed surprisingly that the three non frequency-specific TMS patterns did not prevent a build-up of local high-beta activity. Nonetheless, they increased power across broader or in multiple frequency bands compared to control purely rhythmic high-beta bursts tested along. Importantly, non frequency-specific patterns enhanced signal entropy over multiple time-scales, suggesting higher complexity and an overall induction of higher levels of cortical noise than rhythmic TMS bursts. Our outcomes provide indirect evidence on a potential modulatory role played by sources of stochastic noise on brain oscillations and synchronization. Additionally, they pave the way towards the development of novel neurostimulation approaches to manipulate cortical sources of noise and further investigate their causal role in neural coding.
Characterizing the short-latency evoked response to intracortical microstimulation across a multi-electrode array
Authors: Sombeck Joseph , Heye Juliet , Kumaravelu Karthik , Goetz Stefan M. , Peterchev Angel V. , Grill Warren M. , Bensmaia Sliman , Miller Lee E.
Published: November 2021

Objective

Persons with tetraplegia can use brain-machine interfaces to make visually guided reaches with robotic arms. Without somatosensory feedback, these movements will likely be slow and imprecise, like those of persons who retain movement but have lost proprioception. Intracortical microstimulation (ICMS) has promise for providing artificial somatosensory feedback. If ICMS can mimic naturally occurring neural activity, afferent interfaces may be more informative and easier to learn than interfaces that evoke unnaturalistic activity. To develop such biomimetic stimulation patterns, it is important to characterize the responses of neurons to ICMS.

Approach

Using a Utah multi-electrode array, we recorded activity evoked by single pulses, and short (~0.2 s) and long (~4 s) trains of ICMS at a wide range of amplitudes and frequencies. As the electrical artifact caused by ICMS typically prevents recording for many milliseconds, we deployed a custom rapid-recovery amplifier with nonlinear gain to limit signal saturation on the stimulated electrode. Across all electrodes after stimulation, we removed the remaining slow return to baseline with acausal high-pass filtering of time-reversed recordings. With these techniques, we could record ~0.7 ms after stimulation offset even on the stimulated electrode.

Main results

We recorded likely transsynaptically-evoked activity as early as ~0.7 ms after single pulses of stimulation that was immediately followed by suppressed neural activity lasting 10–150 ms. Instead of this long-lasting inhibition, neurons increased their firing rates for ~100 ms after trains. During long trains, the evoked response on the stimulated electrode decayed rapidly while the response was maintained on non-stimulated channels.

Significance

The detailed description of the spatial and temporal response to ICMS can be used to better interpret results from experiments that probe circuit connectivity or function of cortical areas. These results can also contribute to the design of stimulation patterns to improve afferent interfaces for artificial sensory feedback.
A Field-Deployable Diagnostic Assay for the Visual Detection of Misfolded Prions
Authors: Christenson Peter R. , Li Manci , Rowden Gage , Schwabenlander Marc , Wolf Tiffany M. , Oh Sang-Hyun , Larsen Peter A.
Published: November 2021

Chronic Wasting Disease (CWD), a prion disease of cervids, has been identified across North America, Northern Europe and Korea. Diagnostic tools for the rapid and reliable detection of prion diseases are limited. Here, we combine gold nanoparticles (AuNPs) and quaking induced conversion (QuIC) technologies for the visual detection of amplified misfolded prion proteins from tissues of wild white-tailed deer infected with Chronic Wasting Disease (CWD). Our newly developed diagnostic test, MN-QuIC, enables both naked-eye and light-absorbance measurements for the detection of misfolded prions. The MN-QuIC assay leverages basic laboratory equipment that is cost-effective and portable, thus facilitating real-time prion diagnostics across a variety of settings. To test the portability of our assay, we deployed to a rural field station in southeastern Minnesota and tested for CWD on site. We successfully demonstrated that MN-QuIC is functional in a non-traditional laboratory setting by performing a blinded analysis in the field and correctly identifying all CWD positive and CWD not detected (independently confirmed with ELISA and/or IHC tests) animals at the field site, thus documenting the portability of the assay. Additionally, we show that electrostatic forces and concentration effects help govern the AuNP/prion interactions and contribute to the differentiation of CWD-prion positive and negative samples. We examined 17 CWD-positive and 24 CWD-not-detected white-tailed deer tissues that were independently tested using ELISA, IHC, and RT-QuIC technologies, and results secured with MN-QuIC were 100% consistent with these tests. We conclude that hybrid AuNP and QuIC assays, such as MN-QuIC, have great potential for sensitive, field-deployable diagnostics for a variety of protein misfolding diseases.
Effects of the expression of random sequence clones on growth and transcriptome regulation in Escherichia coli
Authors: Bhave Devika , Tautz Diethard
Published: November 2021

Comparative genomic analyses have provided evidence that new genetic functions can emerge out of random nucleotide sequences. Here, we apply a direct experimental approach to study the effects of plasmids harbouring random sequence inserts under the control of an inducible promoter. Based on data from previously described experiments dealing with the growth of clones within whole libraries, we extracted specific clones that had shown either negative or positive effects on relative cell growth. We analysed these individually with respect to growth characteristics and impact on the transcriptome. We find that candidate clones for negative peptides lead to growth arrest by eliciting a general stress response. Overexpression of positive clones, on the other hand, does not change the exponential growth rates of hosts, but they show a growth advantage over a neutral candidate clone when tested in direct competition experiments. Transcriptomic changes in positive clones are relatively moderate and specific to each clone. We conclude from our experiments that random sequence peptides are indeed a suitable source for the de novo evolution of genetic functions.
Transcriptional and mutational signatures of the aging germline
Authors: Witt Evan , Langer Christopher B , Svetec Nicolas , Zhao Li
Published: November 2021

Aging is a complex biological process that is accompanied by changes in gene expression and mutational load. In many species, including humans, older fathers pass on more paternally-derived de novo mutations; however, the cellular basis and cell types driving this pattern are still unclear. To explore the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissues from the same flies. We found that early germ cells from old and young flies enter spermatogenesis with similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. Mutations in old cells may also increase during spermatogenesis. Our data reveal that old and young flies have distinct mutational biases. Many classes of genes show increased post-meiotic expression in the germlines of older flies. Late spermatogenesis-enriched genes have higher dN/dS than early spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is a source of evolutionary innovation. Surprisingly, young fly enriched genes show higher dN/dS than old fly enriched genes. Our results provide novel insights into the role of the germline in de novo mutation.
Identification of biological processes and signaling pathways for the knockout of REV-ERB in mouse brain
Authors: Li Jing , Wang Wei , Gu Hanming
Published: November 2021

REV-ERB is an orphan nuclear receptor that is widely expressed in the brain and inhibits transcriptional activities. A variety of genes affect the activity and expression of REV-ERB. In this study, our objective is to identify significant signaling pathways and biological processes in the knockout of the REV-ERB mouse brain. The GSE152919 dataset was originally created by using the Illumina HiSeq 4000 (Mus musculus). The KEGG and GO analyses suggested that biological processes “PPAR signaling”, “Hippo signaling”, and “Hypertrophic cardiomyopathy (HCM)” are mostly affected in the knockout of REV-ERB. Furthermore, we identified a number of genes according to the PPI network including NPAS2, CRY2, BMAL1, and CRY1 which were involved in the lack of REV-ERB in the brain. Therefore, our study provides further insights into the study of circadian clocks.
Somatic regulation of female germ cell regeneration and development in planarians
Authors: Khan Umair W. , Newmark Phillip A.
Published: November 2021

Female germ cells develop into oocytes, with the capacity for totipotency. In most animals, these remarkable cells are specified during development and cannot be regenerated. By contrast, planarians, known for their regenerative prowess, can regenerate germ cells. To uncover mechanisms required for female germ cell development and regeneration, we generated gonad-specific transcriptomes and identified genes whose expression defines progressive stages of female germ cell development. Strikingly, early female germ cells share molecular signatures with the pluripotent stem cells driving planarian regeneration. We uncovered spatial heterogeneity within somatic ovarian cells and found that a regionally enriched FoxL homolog is required for oocyte differentiation, but not specification, suggestive of functionally distinct somatic compartments. Unexpectedly, a neurotransmitter-biosynthetic enzyme, AADC, is also expressed in somatic gonadal cells, and plays opposing roles in female and male germ cell development. Thus, somatic gonadal cells deploy conserved factors to regulate germ cell development and regeneration in planarians.
Fine-tuning of deep language models as a computational framework of modeling listeners’ perspective during language comprehension
Authors: Tikochinski Refael , Goldstein Ariel , Yeshurun Yaara , Hasson Uri , Reichart Roi
Published: November 2021

Computational Deep Language Models (DLMs) have been shown to be effective in predicting neural responses during natural language processing. This study introduces a novel computational framework, based on the concept of fine-tuning (Hinton, 2007), for modeling differences in interpretation of narratives based on the listeners’ perspective (i.e. their prior knowledge, thoughts, and beliefs). We draw on an fMRI experiment conducted by Yeshurun et al. (2017), in which two groups of listeners were listening to the same narrative but with two different perspectives (cheating versus paranoia). We collected a dedicated dataset of ~3000 stories, and used it to create two modified (fine-tuned) versions of a pre-trained DLM, each representing the perspective of a different group of listeners. Information extracted from each of the two fine-tuned models was better fitted with neural responses of the corresponding group of listeners. Furthermore, we show that the degree of difference between the listeners’ interpretation of the story - as measured both neurally and behaviorally - can be approximated using the distances between the representations of the story extracted from these two fine-tuned models. These models-brain associations were expressed in many language-related brain areas, as well as in several higher-order areas related to the default-mode and the mentalizing networks, therefore implying that computational fine-tuning reliably captures relevant aspects of human language comprehension across different levels of cognitive processing.
In Diverse Conditions Intrinsic Chromatin Condensates Have Liquid-like Material Properties
Authors: Gibson Bryan A. , Blaukopf Claudia , Lou Tracy , Doolittle Lynda K. , Finkelstein Ilya , Narlikar Geeta J. , Gerlich Daniel W. , Rosen Michael K.
Published: November 2021

Eukaryotic nuclear DNA is wrapped around histone proteins to form nucleosomes, which further assemble to package and regulate the genome. Understanding of the physical mechanisms that contribute to higher order chromatin organization is limited. Previously, we reported the intrinsic capacity of chromatin to undergo phase separation and form dynamic liquid-like condensates, which can be regulated by cellular factors. Recent work from Hansen, Hendzel, and colleagues suggested these intrinsic chromatin condensates are solid in all but a specific set of conditions. Here we show that intrinsic chromatin condensates are fluid in diverse solutions, without need for specific buffering components. Exploring experimental differences in sample preparation and imaging between these two studies, we suggest what may have led Hansen, Hendzel, and colleagues to mischaracterize the innate properties of chromatin condensates. We also describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained movement of chromatin in cells.
The systematic assessment of completeness of public metadata accompanying omics studies
Authors: Huang Yu-Ning , Jaiswal Pooja Vinod , Rajesh Anushka , Yadav Anushka , Yu Dottie , Liu Fangyun , Scheg Grace , Boldirev Grigore , Nakashidze Irina , Sarkar Aditya , Mehta Jay Himanshu , Wang Ke , Patel Khooshbu Kantibhai , Mirza Mustafa Ali Baig , Hapani Kunali Chetan , Peng Qiushi , Ayyala Ram , Guo Ruiwei , Kapur Shaunak , Ramesh Tejasvene , Abedalthagafi Malak S. , Mangul Serghei
Published: November 2021

Recent advances in high-throughput sequencing technologies have made it possible to collect and share a massive amount of omics data, along with its associated metadata. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data limits the reproducibility and reusability of millions of omics samples. In this study, we performed a comprehensive assessment of metadata completeness shared in both scientific publications and/or public repositories by analyzing over 253 studies encompassing over 164 thousands samples. We observed that studies often omit over a quarter of important phenotypes, with an average of only 74.8% of them shared either in the text of publication or the corresponding repository. Notably, public repositories alone contained 62% of the metadata, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Studies involving non-human samples were more likely to share metadata than studies involving human samples. We observed similar results on the extended dataset spanning 2.1 million samples across over 61,000 studies from the Gene Expression Omnibus repository. The limited availability of metadata reported in our study emphasizes the necessity for improved metadata sharing practices and standardized reporting. Finally, we discuss the numerous benefits of improving the availability and quality of metadata to the scientific community abd beyond, supporting data-driven decision-making and policy development in the field of biomedical research.