bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic expression of HIOMT improves tolerance and nitrogen utilization efficiency in transgenic apple under drought stress
Authors: Liang Bowen , Wei Zhiwei , Ma Changqing , Yin Baoying , Li Chao , Ma Fengwang
Published: September 2022

Melatonin enhances plant tolerance to various environmental stressors. Although exogenous application of melatonin has been investigated, the role of endogenous melatonin metabolism in the response of apples to drought stress and nutrient utilization remains unclear. Here, we investigated the effects of ectopically expressing the human melatonin synthase gene HIOMT on transgenic apple plants under drought stress conditions. The tolerance of transgenic apple lines that ectopically expressed HIOMT improved significantly under drought conditions. After 10 days of natural drought stress treatment, the transgenic apple plants showed higher relative water content, chlorophyll levels and Fv/Fm, and lower relative electrolyte leakage and hydrogen peroxide accumulation, than wild-type plants. The activities of peroxidase, superoxide dismutase and catalase, as well as genes in the ascorbate–glutathione cycle, increased more in transgenic apple plants than in the wild-type. The ectopic expression of HIOMT also markedly alleviated the inhibitory effects of long-term drought stress on plant growth, photosynthetic rate and chlorophyll concentrations in apple plants. The uptake and utilization of 15N increased markedly in the transgenic lines under long-term moderate drought stress. Drought stress sharply reduced the activity of enzymes involved in nitrogen metabolism, but ectopic expression of HIOMT largely reversed that response. The expression levels of genes of nitrogen metabolism and uptake were more upregulated in transgenic apple plants than the wild-type. Overall, our study demonstrates that ectopic expression of HIOMT enhanced the tolerance of apple plants to drought stress, and transgenic apple plants showed improved growth due to higher nutrient utilization efficiency under drought conditions.
Factors Associated with Pressure Injury Among Critically Ill Patients in a Coronary Care Unit
Authors: Ko Eunji , Choi Seunghye
Published: September 2022

Objective

To ascertain the incidence of pressure injuries (PIs) in patients in the coronary care unit (CCU), identify PI characteristics, and determine associated risk factors.

Methods

Researchers conducted a retrospective investigational study of patients’ medical records. A total of 820 patients who were admitted to the CCU between January 2018 and December 2020 met the study criteria. Of these, 200 patients who developed PIs after admission to the CCU were included in this study. This study examined the clinical features of PIs, as well as five PI risk factors: patient characteristics; length of stay; intrinsic factors; care factors, including medical devices; and vasopressor agents.

Results

The incidence of PIs among patients in the CCU was 24.4%. At initial detection, 79.5% of these injuries were already at stage 2 or higher. The results indicated a significant correlation between PI stage and hemoglobin level. Moreover, the authors also found relationships between the use of medical devices (eg, arterial catheters, oxygen tubes, and Levin tubes) and PI onset.

Conclusions

Critically ill patients in the CCU use various medical devices for an extended period with severe consequences. The risk factors affecting PI are multifactorial. Therefore, the implementation of PI prevention and early detection strategies for patients in the CCU are crucial.
Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm
Authors: Johnston Karissa M , Powell Lauren , Popoff Evan , Harris Linda , Croop Robert , Coric Vladimir , L’Italien Gilbert
Published: September 2022

Objectives:

To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials.

Methods:

A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo.

Results:

Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: −2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea.

Conclusions:

The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.
Type 1 interferon activation in systemic sclerosis: a biomarker, a target or the culprit
Authors: Kakkar Vishal , Assassi Shervin , Allanore Yannick , Kuwana Masataka , Denton Christopher P. , Khanna Dinesh , Del Galdo Francesco
Published: September 2022

Purpose of review

Activation of the type 1 interferon (T1 IFN) pathway has been implicated in the pathogenesis of systemic sclerosis (SSc) by an increasing number of studies, most of which share key findings with similar studies in systemic lupus erythematosus (SLE). Here we will focus on the evidence for T1 IFN activation and dysregulation in SSc, and the rationale behind targeting the pathway going forward.

Recent findings

An increased expression and activation of T1 IFN-regulated genes has been shown to be present in a significant proportion of SSc patients. TI IFN activation markers have been found to predict and correlate with response to immunosuppressive treatment as well as severity of organ involvement. As inhibition of the IFN-α receptor has been proven to be effective in active SLE, benefit may be seen in targeting the IFN pathway in SSc.

The role played by T1 IFN and its regulatory genes in SSc is becoming increasingly evident and strikingly similar to the role observed in SLE. This observation, together with the benefit of type 1 IFN targeting in SLE, supports the notion of a potential therapeutic benefit in targeting T1 IFN in SSc.
Residual elbow instability in children with posterior or postero-lateral elbow dislocation
Authors: Bettuzzi Camilla , Lucchesi Giovanni , Salvatori Giada , Fruttero Chiara , Orlando Natalie , Antonioli Diego , Canavese Federico , Lampasi Manuele
Published: September 2022

The purpose of this study is to evaluate the incidence and the severity of residual elbow instability in children treated for posterior (PED) or postero-lateral (PLED) elbow dislocation. This retrospective study included all children younger than 14 years of age with a confirmed diagnosis of acute post-traumatic elbow dislocation (ED). Subjective data such as perceived pain, stiffness and impact of daily activities, and objective data such as skin lesions, surgical-site infections, and range of motion were recorded. All patients underwent the milking test, the chair sign test (CST) and the Drawer test (DT). The functional status has been rated according to the Mayo Elbow Performance Score (MEPS) and the Roberts criteria (RC). Radiographs of the injured arm were performed at the last follow-up visit to evaluate axial alignment, growth disturbances, osteoarthrosis, heterotopic calcifications, and the presence of loose intra-articular bodies. Nineteen patients with a mean age of 9 years and 5 months at the time of injury were available for review. Six patients had PED (31.6%) and 13 PLED (68.4%); in five cases (26.3%) the dislocation was simple and in 14 cases (73.7%) it was complex. None of the patients complained of subjective symptoms of elbow instability, although 2 patients had positive CST, and one of them also had positive milking test. RC and MEPS ranged from good to excellent in all patients. Clinical examination with multiple stability tests is important to detect residual elbow instability in children treated for ED as functional scores alone may underestimate the clinical picture.
An Alternative Perspective on the Robust Poisson Method for Estimating Risk or Prevalence Ratios
Authors: Talbot Denis , Mésidor Miceline , Chiu Yohann , Simard Marc , Sirois Caroline
Published: September 2022

The robust Poisson method is becoming increasingly popular when estimating the association of exposures with a binary outcome. Unlike the logistic regression model, the robust Poisson method yields results that can be interpreted as risk or prevalence ratios. In addition, it does not suffer from frequent nonconvergence problems such as the most common implementations of maximum likelihood estimators of the log-binomial model. However, using a Poisson distribution to model a binary outcome may seem counterintuitive. Methodologic papers have often presented this as a good approximation to the more natural binomial distribution. In this article, we provide an alternative perspective to the robust Poisson method based on the semiparametric theory. This perspective highlights that the robust Poisson method does not require assuming a Poisson distribution for the outcome. In fact, the method only assumes a log-linear relation between the risk or prevalence of the outcome and the explanatory variables. This assumption and the consequences of its violation are discussed. We also provide suggestions to reduce the risk of violating the modeling assumption. Additionally, we discuss and contrast the robust Poisson method with other approaches for estimating exposure risk or prevalence ratios. See video abstract at, http://links.lww.com/EDE/B987.
Dufourmentel Flap for Scalp Reconstruction
Authors: Viciana Enrique J. , Lessard Anne-Sophie
Published: September 2022

Transposition flaps are useful for reconstruction of many skin defects. Limberg described a rhomboid rotation flap in 1946. Dufourmentel described an improved version of the Limberg flap in 1962. The Dufourmentel flap is also a quadrangular rhomboid flap which can be used in any area of the body except for the central face, the fingers, and the volar hand. The design of the Dufourmentel flap creates a wider base for this random flap, thus making it more reliable. Where tissue loss is significant, or where skin and soft tissue elasticity is limited, double opposing Dufourmentel flaps are useful. A variation of the Dufourmentel flap is described where a circular defect is converted to a square. The line of greatest extensibility is marked through the circular defect or lesion. A square is marked around the circle with one corner of the square tilted 10–20 degrees counterclockwise from the line of greatest extensibility. After marking corners A, B, C, and D, lines are marked extending BD and CD. The first incision, DE, will bisect the angle created by extending BD and CD. The second incision, EF, is roughly perpendicular to CD extended, but the angle at E is opened up a bit to create a wider base for the flap. Point D will rotate to point B, E rotates to C, and F translates to D. The invisible line DF should be approximately parallel to the line of greatest extensibility. When the defect is relatively large or where the surrounding tissues have limited elasticity, the above-described ideal variation of the Dufourmentel flap may not be possible because the flap may not rotate and advance all the way around without tension. In this case, double opposing Dufourmentel type flaps have been found to be useful by meeting each other at the halfway point.
Pediatric Patient and Caregiver Satisfaction With the Use of Transabdominal Bowel Ultrasound in the Assessment of Inflammatory Bowel Diseases
Authors: Hudson Alexandra S. , Huynh Hien Q. , Novak Kerri L. , Ma Henry , Kuc Anna , Kim Justin , Almeida Patricia , Carroll Matthew W. , Wine Eytan , Isaac Daniela M.
Published: September 2022

Objectives:

Transabdominal bowel ultrasound (TABUS) is emerging as an attractive, noninvasive tool in inflammatory bowel disease (IBD). Patient and caregiver experience with TABUS is not well described. We aimed to determine pediatric patient and caregiver satisfaction with TABUS and the impact of IBD severity, gender, age, and a history of anxiety on satisfaction.

Methods:

Pediatric patients (0–18 years old) with suspected IBD prospectively underwent baseline TABUS, magnetic resonance enterography (MRE), blood work, stool studies, and endoscopy. Patients and their caregiver each completed a cross‐sectional satisfaction questionnaire (5‐point Likert scale) after the baseline investigations.

Results:

There were 54 patients included (67% male). The majority were completely satisfied and strongly agree TABUS was better tolerated than other investigations, regardless of disease severity (P > 0.05). Patients with higher Simple Endoscopic Score for Crohn Disease (SES‐CD) scores felt that TABUS increased their understanding of their IBD (P < 0.05) and disease location (P < 0.05). Patients with Crohn disease had similar responses to those with ulcerative colitis, but more strongly agreed that TABUS was better than MRE and endoscopy (P < 0.05). Those with anxiety did not have an increased level of worry about potential ultrasound findings (P > 0.05).

Conclusions:

Pediatric patients and their caregivers were highly satisfied with TABUS, preferring it to other modalities. It did not lead to increased worry, and was particularly important in those with severe IBD. These findings support wider implementation of this well tolerated and preferred monitoring tool in pediatrics.
Pediatric Endoscopy Blocks
Authors: Barakat Monique T. , Pei Francesca , Gugig Roberto
Published: September 2022

Objectives:

Endoscopic procedures are increasingly performed for children and adolescents and these interventions represent a central element of both pediatric gastroenterology (GI) care and revenues. It remains unclear, however, which scheduling paradigm maximizes efficiency of resource utilization and delivery of care in this arena. In this study, we evaluate the impact of shifting from shared endoscopy blocks to individual, provider‐specific endoscopy blocks for scheduling endoscopic procedures in our tertiary care academic center.

Methods:

The implemented endoscopy block system involves a single endoscopist performing procedures in an allocated room for the entire half‐day period of time, with most providers having 1–3.5 day blocks per month. We analyzed block fragmentation (multiple providers in a single block), block utilization, and procedure volume, comparing the 8‐month period prior to implementation of the block system (pre‐implementation period) with the 8‐month period following implementation of the block system (post‐implementation period). Provider satisfaction and perceptions were assessed by survey pre‐ and post‐implementation. Standard descriptive statistics were utilized for analysis.

Results:

In the pre‐ and post‐implementation periods, 22 half‐day blocks were allocated to pediatric GI. In the pre‐implementation period, mean utilization of these blocks was 65.9% (range: 47%–77%). In the post‐implementation period, mean % utilization was 79.8% (range: 64%–89%). Overall endoscopy procedure volume increased from 279 in the pre‐implementation period to 419 in the post‐implementation period. Provider perception of endoscopy efficiency was enhanced by the block system, with 68.4% of pediatric GI respondents rating endoscopy as “efficient” post‐implementation (vs 19% pre‐implementation) and 63.2% indicating that the block system directly enhanced efficiency. A total of 63.2% reported increased personal procedure volume and 84.2% reported perceived increase in overall procedure volume with block system implementation.

Conclusions:

Strategic approaches for scheduling endoscopic procedures carry the potential to enhance efficiency and experience for both providers and patients. Implementation of the endoscopy block system was associated with increased procedure volumes and block utilization as well as a more positive experience for the majority of providers. Schedule adjustments with analysis of associated efficiency and satisfaction metrics can optimize pediatric endoscopy practice.
Comprehensive Diagnostic Criteria for MELAS Syndrome; a Case Study Involving an Elderly Patient With MT-TWm.5541C>T Mutation
Authors: Wu Gang , Shen Yuguang , Zhu Feng , Tao Weiwei , Zhou Yuanlin , Ke Shaofa , Jiang Huihua
Published: September 2022

Introduction:

The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS.

Case Report:

A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes.

Conclusion:

Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.
“Pediatric Outcomes Following Cranial Vault Remodeling with Restricted Use of Post-Operative Narcotics, a Retrospective Review.”
Authors: Smith Kayla J , Cimaroli Sawyer , Loo Rory , Havlik Robert J , Denny Arlen D , Klement Kristen A
Published: September 2022

Background:

The appropriate use of narcotics for post-operative pain control is controversial due to potential medication induced complications. We seek to determine the effects of narcotics in the pediatric population following cranial vault remodeling surgeries.

Methods:

A retrospective review was performed on 160 consecutive patients who underwent cranial vault remodeling for craniosynostosis.

Results:

There was a statistically significant difference in total morphine equivalents in the group that experienced no emesis and those with at least one episode of emesis (0.97 morphine equivalents/kg vs 1.44 morphine equivalents/kg, p=0.05). There was a statistically significant difference in hospital morphine equivalents in the group with documented respiratory events, average of 2.3 morphine equivalents/kg versus 1.3, in the nonevent group (p=0.006). The patients that received dexmedetomidine had trend towards a decrease in hospital narcotic administration with equivalent pain control (1.2 morphine equivalents/kg versus 1.9, p = 0.09). There was a statistically significant positive correlation between total morphine equivalents for the hospitalization and hospital stay (r=0.27, p=0.001). The amount of morphine equivalents used in the first 24 hours was also found to be an independent predictor of a respiratory event (p=0.002 by multivariate logistic regression). Independent positive predictors of hospital stay were age (p< 0.001), ICU time (p<0.001), and total morphine equivalents for the hospitalization (p= 0.001) by multivariate analysis with linear regression.

Conclusions:

Our study demonstrates improvement in outcomes with decreased use of narcotics, which establishes that there is a need to further explore post-surgical recovery outcomes with multimodal pain control.
The Prevalence, Incidence, and Risk Factors for HIV Among Female Sex Workers—A Cohort Being Prepared for a Phase IIb HIV Vaccine Trial in Dar es Salaam, Tanzania
Authors: Faini Diana , Msafiri Frank , Munseri Patricia , Bakari Muhammad , Lyamuya Eligius , Sandström Eric , Biberfeld Gunnel , Nilsson Charlotta , Hanson Claudia , Aboud Said
Published: September 2022

Background:

A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial (PrEPVacc).

Setting:

A cohort of FSWs in Dar es Salaam, Tanzania.

Methods:

FSWs aged 18–45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate.

Results:

Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25–5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18–24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV.

Conclusion:

The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.
Enhancing oxidative phosphorylation over glycolysis for energy production in cultured mesenchymal stem cells
Authors: Monsour Molly , Gorsky Anna , Nguyen Hung , Castelli Vanessa , Lee Jea-Young , Borlongan Cesar V.
Published: September 2022

Objective

Strokes represent as one of the leading causes of death and disability in the USA, however, there is no optimal treatment to reduce the occurrence or improve prognosis. Preconditioning of tissues triggers ischemic tolerance, a physiological state that may involve a metabolic switch (i.e. from glycolysis to oxidative phosphorylation or OxPhos) to preserve tissue viability under an ischemic insult. Here, we hypothesized that metabolic switching of energy source from glucose to galactose in cultured mesenchymal stem cells (MSCs) stands as an effective OxPhos-enhancing strategy.

Methods

MSCs were grown under ambient condition (normal MSCs) or metabolic switching paradigm (switched MSCs) and then assayed for oxygen consumption rates (OCR) and extracellular acidification rate (ECAR) using the Seahorse technology to assess mitochondrial respiration.

Results

Normal MSCs showed a lower OCR/ECAR ratio than switched MSCs at baseline (P < 0.0001), signifying that there were greater levels of OxPhos compared to glycolysis in switched MSCs. By modulating the mitochondrial metabolism with oligomycin (time points 4–6), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (7–9), and rotenone and antimycin (time points 10–12), switched MSCs greater reliance on OxPhos was further elucidated (time points 5–12; P < 0.0001; time point 4; P < 0.001).

Conclusion

The metabolic switch from glycolytic to oxidative metabolism amplifies the OxPhos potential of MSCs, which may allow these cells to afford more robust therapeutic effects against neurological disorders that benefit from ischemic tolerance.
Association analysis of risk genes identified by SCHEMA with schizophrenia in the Chinese Han population
Authors: Guo Aiguo , Lun Peng , Chen Jianhua , Li Qinghua , Chang Kaihui , Li Teng , Pan Dun , Zhang Jinmai , Zhou Juan , Wang Ke , Zhang Qian , Yang Qiangzhen , Gao Chengwen , Wu Chuanhong , Jian Xuemin , Wen Yanqin , Wang Zhuo , Shi Yongyong , Zhao Xiangzhong , Sun Peng , Li Zhiqiang
Published: September 2022

Background

Schizophrenia is a chronic brain disorder. Previously, the Schizophrenia Exome Sequencing Meta-analysis consortium identified 10 highest risk genes related to schizophrenia. This study aimed to analyze the relationship between the 10 highest risk genes identified by the SCHEMA and schizophrenia in a Chinese population.

Methods

A total of 225 variants in 10 genes were screened in a Chinese population of 6836 using a customized array. All variants were annotated through the Variant Effect Predictor tool, and the functional impacts of missense variants were assessed based on sorting intolerant from tolerant and PolyPhen-2 scores. The SHEsisPlus tool was used to analyze the association between risk genes and schizophrenia at the locus and gene levels.

Results

At the locus level, no missense variants significantly related to schizophrenia were found, but we detected three missense variants that appeared only in cases, including TRIO p. Arg1185Gln, RB1CC1 p. Arg1514Cys, and HERC1 p. Val4517Leu. At the gene level, five genes (TRIO, RB1CC1, HERC1, GRIN2A, and CACAN1G) with more than one variant analyzed were kept for the gene-level association analysis. Only the association between RB1CC1 and schizophrenia reached a significant level (OR = 1.634; 95% CI, 1.062–2.516; P = 0.025).

Conclusion

In this study, we determined that RB1CC1 might be a risk gene for schizophrenia in the Chinese population. Our results provide new evidence for recognizing the correlation of these risk genes with the Chinese schizophrenia population.
Novel RPS6KA3 mutations cause Coffin-Lowry syndrome in two patients and concurrent compulsive eyebrow-pulling behavior in one of them
Authors: Gürsoy Semra , Hazan Filiz , Çetinoğlu Elif
Published: September 2022

Coffin-Lowry syndrome (CLS) is a rare X-linked disorder that, usually affects males, presenting with intellectual disability, short stature, growth retardation, short hands, hyperextensible fingers and progressive kyphoscoliosis. Due to skewed X chromosome inactivation, the clinical presentations of the affected females vary greatly and clinical manifestations could range from mild intellectual disability to typical features of CLS in males. Here, we reported two different novel RPS6KA3 gene mutations in two unrelated CLS patients and also described concomitant compulsive eyebrow-pulling behavior in one of these cases for the first time in the literature.
Avian behaviour changes in response to human activity during the COVID-19 lockdown in the United Kingdom
Authors: Warrington Miyako H. , Schrimpf Michael B. , Des Brisay Paulson , Taylor Michelle E. , Koper Nicola
Published: September 2022

Human activities may impact animal habitat and resource use, potentially influencing contemporary evolution in animals. In the United Kingdom, COVID-19 lockdown restrictions resulted in sudden, drastic alterations to human activity. We hypothesized that short-term daily and long-term seasonal changes in human mobility might result in changes in bird habitat use, depending on the mobility type (home, parks and grocery) and extent of change. Using Google human mobility data and 872 850 bird observations, we determined that during lockdown, human mobility changes resulted in altered habitat use in 80% (20/25) of our focal bird species. When humans spent more time at home, over half of affected species had lower counts, perhaps resulting from the disturbance of birds in garden habitats. Bird counts of some species (e.g. rooks and gulls) increased over the short term as humans spent more time at parks, possibly due to human-sourced food resources (e.g. picnic refuse), while counts of other species (e.g. tits and sparrows) decreased. All affected species increased counts when humans spent less time at grocery services. Avian species rapidly adjusted to the novel environmental conditions and demonstrated behavioural plasticity, but with diverse responses, reflecting the different interactions and pressures caused by human activity.
Naming the unnamed: over 65,000 Candidatus names for unnamed Archaea and Bacteria in the Genome Taxonomy Database
Authors: Pallen Mark J. , Rodriguez-R Luis M. , Alikhan Nabil-Fareed
Published: September 2022

Thousands of new bacterial and archaeal species and higher-level taxa are discovered each year through the analysis of genomes and metagenomes. The Genome Taxonomy Database (GTDB) provides hierarchical sequence-based descriptions and classifications for new and as-yet-unnamed taxa. However, bacterial nomenclature, as currently configured, cannot keep up with the need for new well-formed names. Instead, microbiologists have been forced to use hard-to-remember alphanumeric placeholder labels. Here, we exploit an approach to the generation of well-formed arbitrary Latinate names at a scale sufficient to name tens of thousands of unnamed taxa within GTDB. These newly created names represent an important resource for the microbiology community, facilitating communication between bioinformaticians, microbiologists and taxonomists, while populating the emerging landscape of microbial taxonomic and functional discovery with accessible and memorable linguistic labels.
The impact of cognitive ability on multitalker speech perception in neurodivergent individuals
Authors: Lau Bonnie K. , Emmons Katherine , Maddox Ross K. , Estes Annette , Dager Stephen , (Astley) Hemingway Susan J. , Lee Adrian KC
Published: September 2022

The ability to selectively attend to one talker in the presence of competing talkers is crucial to communication. Here we investigate whether cognitive deficits in the absences of hearing loss can impair speech perception. We tested typical hearing, neurodivergent adolescents/adults with autism spectrum disorder, fetal alcohol spectrum disorder, and an age- and sex-matched neurotypical group. We found a strong correlation between IQ and speech perception, with individuals with lower IQ scores having worse speech thresholds. These results demonstrate that deficits in cognitive ability, despite intact peripheral encoding, can impair listening under complex conditions. These findings have important implications for conceptual models of speech perception and for audiological services to improve communication in real-world environments for neurodivergent individuals.
Volumetric Imaging of Human Mesenchymal Stem Cells (hMSCs) for Non-Destructive Quantification of 3D Cell Culture Growth
Authors: Benavides Oscar R. , Gibbs Holly C. , White Berkley P. , Kaunas Roland , Gregory Carl A. , Maitland Kristen C.
Published: September 2022

The adoption of cell-based therapies into the clinic will require tremendous large-scale expansion to satisfy future demand, and bioreactor-microcarrier cultures are best suited to meet this challenge. The use of spherical microcarriers, however, precludes in-process visualization and monitoring of cell number, morphology, and culture health. The development of novel expansion methods also motivates the advancement of analytical methods used to characterize these microcarrier cultures. A robust optical imaging and image-analysis assay to non-destructively quantify cell number and cell volume was developed. This method preserves 3D cell morphology and does not require membrane lysing, cellular detachment, or exogenous labeling. Complex cellular networks formed in microcarrier aggregates were imaged and analyzed in toto. Direct cell enumeration of large aggregates was performed in toto for the first time. This assay was successfully applied to monitor cellular growth of mesenchymal stem cells attached to spherical hydrogel microcarriers over time. Elastic scattering and fluorescence lightsheet microscopy were used to quantify cell volume and cell number at varying spatial scales. The presented study motivates the development of on-line optical imaging and image analysis systems for robust, automated, and non-destructive monitoring of bioreactor-microcarrier cell cultures.
A multiplex platform to identify mechanisms and modulators of proteotoxicity in neurodegeneration
Authors: Resnick Samuel J. , Qamar Seema , Sheng Jenny , Huang Lei Haley , Nixon-Abell Jonathon , Melore Schuyler , Chung Chyi Wei , Li Xuecong , Wang Jingshu , Zhang Nancy , Shneider Neil A. , Kaminski Clemens F. , Ruggeri Francesco Simone , Kaminski Schierle Gabriele S. , George-Hyslop Peter St , Chavez Alejandro
Published: September 2022

Neurodegenerative disorders are a family of diseases that remain poorly treated despite their growing global health burden. A shared feature of many neurodegenerative disorders is the accumulation of toxic misfolded proteins. To gain insight into the mechanisms and modulators of protein misfolding, we developed a multiplex reverse genetics platform. Using this novel platform 29 cell-based models expressing proteins that undergo misfolding in neurodegeneration were probed against more than a thousand genetic modifiers. The resulting data provide insight into the nature of modifiers that act on multiple misfolded proteins as compared to those that show activity on only one. To illustrate the utility of this platform, we extensively characterized a potent hit from our screens, the human chaperone DNAJB6. We show that DNAJB6 is a general modifier of the toxicity and solubility of multiple amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD)-linked RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1. Biophysical examination of DNAJB6 demonstrated that it co-phase separates with, and alters the behavior of FUS containing condensates by locking them into a loose gel-like state which prevents their fibrilization. Domain mapping and a deep mutational scan of DNAJB6 support the critical importance for DNAJB6 phase separation in its effects on multiple RNA-binding proteins. Crucially, these studies also suggest that this property can be further tuned to generate novel variants with enhanced activity that might illuminate potential avenues for clinical translation.
The Clostridioides difficile S-Layer Protein A (SlpA) serves as a general phage receptor
Authors: Royer Alexia L.M. , Umansky Andrew A. , Allen Marie-Maude , Garneau Julian R. , Ospina-Bedoya Maicol , Kirk Joseph A. , Govoni Gregory , Fagan Robert P. , Soutourina Olga , Fortier Louis-Charles
Published: September 2022

Therapeutic bacteriophages (phages) are being considered as alternatives in the fight against Clostridioides difficile infections. To be efficient, phages should have a wide host range, but the lack of knowledge about the cell receptor used by C. difficile phages hampers the rational design of phage cocktails. Recent reports suggested that the C. difficile surface layer protein A (SlpA) is an important phage receptor, but clear and unambiguous experimental evidence is lacking. Here, using the epidemic R20291 strain and its FM2.5 mutant derivative lacking a functional S-layer, we show that the absence of SlpA renders cells completely resistant to infection by phiCD38-2, phiCDIII and phiCD146, which normally infect the parental strain. Complementation assays with 12 different Slayer Cassette Types (SLCTs) expressed from a plasmid revealed that SLCT-6 also allowed infection by phiCD111, and SLCT-11 enabled infection by phiCD38-2 and phiCD146. Of note, expression of SLCTs 1, 6, 8, 9, 10 or 12 conferred susceptibility to infection by 5 myophages that normally do not infect the R20291 strain, namely phiMMP02, phiMMP03, phiMMP04, phiCD506 and phiCD508. Adsorption assays showed that >50% adsorption was required for productive phage infection. Altogether, our data suggest that many phages use SlpA as their receptor and most importantly, morphologically distinct phages of the Siphoviridae and Myoviridae families target SlpA despite major differences in their tail structures. Our study therefore represents an important breakthrough in our understanding of the molecular interaction between C. difficile and its phages.

IMPORTANCE

Phage therapy represents an interesting alternative to treat Clostridioides difficile infections because contrary to antibiotics, most phages are highly species-specific, thereby sparing the beneficial gut microbes that protect from infection. However, currently available phages against C. difficile have a narrow host range and target members from only one or a few PCR ribotypes. Without a clear comprehension of the factors that define host specificity, and in particular the host receptor recognized by phages, it is hard to develop therapeutic cocktails in a rational manner. In our study, we provide clear and unambiguous experimental evidence that SlpA is a common receptor used by many siphophages and myophages. Although work is still needed to define how a particular phage RBP binds to a specific SLCT, identification of SlpA as a common receptor is a major keystone that will facilitate the rational design of therapeutic phage cocktails against clinically important strains.
Getting Smaller by Denaturation: Acid-Induced Compaction of Antibodies
Authors: Imamura Hiroshi , Ooishi Ayako , Honda Shinya
Published: September 2022

Protein denaturation is a ubiquitous process that occurs bothin vitroandin vivo. While the molecular understanding of the denatured structures of proteins is limited, it is commonly accepted that the loss of unique intramolecular contacts makes proteins larger. Herein, we report compaction of the immunoglobulin G1 (IgG1) protein upon acid denaturation. Small-angle X-ray scattering coupled with size exclusion chromatography revealed that IgG1 radii of gyration at pH 2 were ∼75% of those at a neutral pH. Scattering profiles showed a compact globular shape, supported by analytical ultracentrifugation. The acid denaturation of proteins with size reduction is energetically costly, and acid-induced compaction requires an attractive force for domain reorientation. Such intramolecular aggregation may be widespread in immunoglobulin proteins as non-canonical structures. Herein, we discuss the potential biological significance of these non-canonical structures of antibodies.
Functional conservation of Anopheline linalool receptors through 100 million years of evolution
Authors: Huff Robert M. , Pitts R. Jason
Published: September 2022

Insects rely on olfactory receptors to detect and respond to diverse environmental chemical cues. Detection of semiochemicals by these receptors modulates insect behavior and has a direct impact on species fitness. Volatile organic compounds (VOCs) are released by animals and plants and can provide contextual cues that a blood meal host or nectar source is present. One such VOC is linalool, an enantiomeric monoterpene, that is emitted from plants and bacteria species. This compound exists in nature as one of two possible stereoisomers, (R)-(–)-linalool or (S)-(+)-linalool. In this study, we use a heterologous expression system to demonstrate differential responsiveness of a pair of Anopheline odorant receptors (Ors) to enantiomers of linalool. The mosquitoes Anopheles gambiae and Anopheles stephensi encode single copies of Or29 and Or53, which are expressed in the labella of An. gambiae. (S)-(+)-linalool activates Or29 orthologs with a higher potency than (R)-(–)-linalool, while the converse is observed for Or53 orthologs. The conservation of these receptors across a broad range of Anopheline species suggests they may function in the discrimination of linalool stereoisomers, thereby influencing the chemical ecology of mosquitoes. One potential application of this knowledge would be in the design of novel attractants or repellents to be used in integrated pest management practices.
PrimedSherlock: A tool for rapid design of highly specific CRISPR-Cas12 crRNAs
Authors: Mann James G. , Pitts R. Jason
Published: September 2022

Background

CRISPR-Cas based diagnostic assays provide a portable solution which bridges the benefits of qRT-PCR and serological assays in terms of portability, specificity and ease of use. CRISPR-Cas assays are rapidly fieldable, specific and have been rigorously validated against a number of targets, including HIV and vector-borne pathogens. Recently, CRISPR-Cas12 and CRISPR-Cas13 diagnostic assays have been granted FDA approval for the detection of SARS-CoV-2. A critical step in utilizing this technology requires the design of highly-specific and efficient CRISPR RNAs (crRNAs) and isothermal primers. This process involves intensive manual curation and stringent parameters for design in order to minimize off-target detection while also preserving detection across divergent strains. As such, a single, streamlined bioinformatics platform for rapidly designing crRNAs for use with the CRISPR-Cas12 platform is needed. Here we offer PrimedSherlock, an automated, computer guided process for selecting highly-specific crRNAs and primers for targets of interest.

Results

Utilizing PrimedSherlock and publicly available databases, crRNAs were designed against a selection of Flavivirus genomes, including West Nile, Zika and all four serotypes of Dengue. Using outputs from PrimedSherlock in concert with both wildtype A.s Cas12a and Alt-R Cas12a Ultra nucleases, we demonstrated sensitive detection of nucleic acids of each respective arbovirus in in-vitro fluorescence assays. Moreover, primer and crRNA combinations facilitated the detection of their intended targets with minimal off-target background noise.

Conclusions

PrimedSherlock is a novel crRNA design tool, specific for CRISPR-Cas12 diagnostic platforms. It allows for the rapid identification of highly conserved crRNA targets from user-provided primer pairs or PrimedRPA output files. Initial testing of crRNAs against arboviruses of medical importance demonstrated a robust ability to distinguish multiple strains by exploiting polymorphisms within otherwise highly conserved genomic regions. As a freely-accessible software package, PrimedSherlock could significantly increase the efficiency of CRISPR-Cas12 diagnostics. Conceptually, the portability of detection kits could also be enhanced when coupled with isothermal amplification technologies.
Comparing Narrative Storytelling Ability in Individuals with Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder
Authors: Pham Linh N. H. , Lee Adrian KC , Estes Annette , Dager Stephen , Hemingway Susan J. (Astley) , Thorne John C. , Lau Bonnie K.
Published: September 2022

Purpose

Narrative discourse, or storytelling, is used in daily conversational interaction and reveals higher level language skills that may not be well captured by standardized assessments of language. Many individuals with autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD) show difficulty with pragmatic language skills and narrative production offers one method of assessing expressive and pragmatic language skills in an ecologically relevant manner. This study investigated narrative abilities on both local and global levels of adolescent/young adults with ASD and FASD, and their age- and sex-matched comparison group.

Method

Narratives from forty-five adolescents/young adults, 11 with ASD, 11 with FASD, 23 age- and sex-matched neurotypical comparison group, were elicited using a wordless storybook. They were then transcribed orthographically, formatted to the Systematic Analyses of Language Transcript (SALT) convention, and scored based on the narrative scoring scheme (NSS).

Additional analyses investigated local language measures such as the number of mental state and temporal relation terms produced, as well as global language measures including the mean length of utterance, total number of different words, total number of words, total number of utterances, rate of speech, and the narrative scoring scheme total score.

Results

On local language measures, no significant group differences were found. On global language measures, many aspects of narrative production in the ASD and FASD groups were comparable to each other and to the comparison group, although important differences were observed for the total number of words produced and rate of speech.

Conclusions

Given significant variability observed within groups, these findings suggest that language abilities should be assessed at an individual level. Future research should also consider additional variables that influence narrative production such as motivation, distractibility, or decision-making of individual subjects.
Application of RGB trichrome staining to the study of human parasites
Authors: González-Luna Juan Diego , Gaytán Francisco
Published: September 2022

Human parasitic infections are major contributors to global disease load, compromising the human life and resulting in considerable morbidity and mortality worldwide. However, many parasitic diseases have been neglected and little investigated in western medicine. Although recently developed molecular techniques have revolutionized the taxonomy of parasites and the parasitic disease diagnosis, histopathology still remains a powerfull tool for the analysis of parasitic diseases, allowing direct observation of the parasite thus providing information about the morphological features of the parasite ifself, and revealing tissue alterations at the parasite-host interface. The recently developed RGB trichrome (acronym for the primary dye components, picrosirius Red, fast Green, and alcian Blue) stains the main components of the extracellular matrix, specifically collagens and proteoglycans. We have applied the RGB tricrome staining to human tissues infected by the main three classes of human parasites: Protozoa (Leishmania donovanii and Toxoplasma gondii), helminths (Trichinella spiralis, Enterobius vermicularis, Dirofilaria spp. and Echinococcus granulosus) and ectoparasites (Demodex folliculorum and Demodex brevis). Trichrome stain results in detailed staining of the parasite microanatomical structure, and highlights host tissue alterations such as granulomatous inflammation, immune cell infiltrate, or increased amount of collagen as a sign of parasite-induced fibrosis. Yet, the use of RGB trichrome, as a complement of hematoxylin and eosin staining, provides additional valuable information to assess parasitic infection histopathology.