bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Early Cognitive Functions in Patients With COVID-19 Infection
Authors: Yildirim Gulfem
Published: October 2022

In December 2019, some pneumonia cases emerged in Wuhan, China. It was named as Coronavirus 2019 (COVID-19) by the World Health Organization.

Patients developed anxiety and sleep problems after treatment. Patients with confirmed COVID-19 (n = 57) admitted to our study and whose treatment was completed 3 months ago were included in the study. This is a case-control study, and 22 patients included the control group. We found statistical significance between the average score of Beck anxiety and Pittsburgh Sleep Quality Index (p = 0.03, p = 0.01).

In our study, we investigated the psychological conditions that may occur in the postacute COVID-19 period. We recommend that patients should be directed to appropriate clinics for rehabilitation. Clinicians must be aware that prompt and correct diagnosis with careful management is essential for recovery.
Herpes, Syphilis, and Human Immunodeficiency Virus Coinfection Among Transgender Women in Central Brazil
Authors: Diniz e Silva Bruno Vinícius , Burgo Godoi Alves Juliana , de Oliveira Brunna Rodrigues , Santos Sousa Ana Livia , Margarida Mykaella Cristina Araújo , dos Santos Paulie Marcelly Ribeiro , de Oliveira Bonfim Flávia Freitas , de Paula Vanessa Salete , Villar Livia Melo , Caetano Karla Antonieta Amorim , Teles Sheila Araújo , Carneiro Megmar Aparecida dos Santos
Published: October 2022

Background

Human herpesvirus 2 (HSV-2) is a major cause of sexually transmitted infections (STIs) worldwide and often occurs synergistically with syphilis, and human immunodeficiency virus (HIV) infection. Transgender women (TGW) are disproportionately affected by STIs. The aim of this study was to estimate the prevalence of HSV-2 monoinfection, and HSV-2, syphilis, and HIV coinfection (triple infection) among TGW in Central Brazil.

Methods

A seroprevalence survey was conducted among TGW in Central Brazil from 2018 to 2019. Participants were recruited using respondent-driven sampling and interviewed about their sociodemographic characteristics and STI risk behaviors, and were tested for antibodies to HSV-2, Treponema pallidum, and HIV. Multivariable logistic regression models were used to identify variables associated with HSV-2 monoinfection and triple infection.

Results

Of the 431 participants, 345 (80%) were positive for HSV-2 antibodies, of whom 36 were HSV-2 immunoglobulin M–positive, and 340 were HSV-2 immunoglobulin G–positive. Human herpesvirus 2 and HIV coinfection, HIV and syphilis coinfection, and triple infection were detected in 38 participants (9.0%), 58 participants (13.8%), and 27 participants (6.4%), respectively. Report of a previous STI was associated with a decreased risk of HSV-2 monoinfection (adjusted odds ratio, 0.39), and an increased risk of triple infection (adjusted odds ratio, 4.4). Participants who reported sex not only with men had a 2.42-fold increased risk of triple infection.

Conclusions

The high prevalence of HSV-2, syphilis, and HIV coinfection among TGW is a cause for concern. Transgender women should be screened for HIV and other STIs. Further studies of risk factors for triple infection among TGW are warranted.
Wastewater Surveillance to Inform Public Health Decision Making in Residential Institutions
Authors: Harris-Lovett Sasha , Nelson Kara L. , Kantor Rose , Korfmacher Katrina Smith
Published: October 2022

Testing sewage (wastewater-based surveillance, or WBS) for pathogens is an increasingly important tool for monitoring the health of populations. During the COVID-19 pandemic, some residential institutions including colleges, prisons, and skilled nursing facilities used facility-level wastewater data to inform their pandemic responses. To understand how these early adopters used WBS data in decision making, we conducted in-depth, semistructured interviews with multiple decision makers at 6 residential institutions in the United States (universities, prisons, and nursing homes) encompassing a total of more than 70 000 residents and staff about interpretation, uses, and limitations of these data. We found that WBS data were used in extremely diverse ways. WBS combined with clinical surveillance informed a wide range of public health actions at residential institutions, including transmission reduction measures, public health communications, and allocation of resources. WBS also served other institutional purposes, such as maintaining relationships with external stakeholders and helping alleviate decision makers' pervasive stress. Recognizing these diverse ways of using WBS data can inform expansion of this practice among institutions as well as development of community-scale systems.
Temporary trend, clinical characteristics and outcomes in HIV and non-HIV patients following liposuction: A propensity-matched analysis
Authors: Yang Fan , Peng Chi , Peng Liwei , He Jia , Jin Zhichao , Li Yuejun
Published: October 2022

Background:

Thanks to the availability of highly active antiretroviral therapy, individuals infected with human immunodeficiency virus (HIV) are enjoying greater longevity, meanwhile, with chronic conditions including abnormal adipose distribution. However, prior data on perioperative outcomes of liposuction in HIV (+) patients were limited by small sample size. Therefore, we aimed to compare differences in temporary trend, clinical characteristics and outcomes between patients with and without HIV who underwent liposuction.

Methods:

The National Inpatient Sample (NIS) database from 2010 to 2017 was queried to identify patients undergoing liposuction. Univariate, multivariate logistic regression and 1:4 propensity score matched analyses were employed to assess the primary outcomes (in-hospital mortality, discharge disposition and postoperative outcomes) and secondary outcomes (prolonged length of stay, total cost).

Results:

Overall, 19936 patients undergoing liposuction were identified, among whom 61 (0.31%) patients were infected with HIV. Patients with HIV were more likely to be male, insured by Medicare, and had more comorbidities with lower income. Unadjusted length of stay was longer among patients with HIV (OR 1.808, 95% CI 1.092–2.994, p = 0.020), nevertheless, multivariable models and propensity score matched analysis demonstrated that patients with HIV were no more likely to undergo complications than the general population. This was also the case for length of stay and total costs.

Conclusions:

Our findings indicated that patients who underwent liposuction with HIV did not experience increased risk of potentially in-hospital major complication or mortality. Liposuction could be safely considered as a surgical treatment for HIV (+) patients with local fat deposition.
Effects of Dose and Injection Site on Gingival Smile Treatment with Botulinum Toxin Type A: A Prospective Study.
Authors: Gong Xi , Yuan Mengning , Gu Chenyang , Yan Boxi , Li Jianjun , Zou Lidong , An Yang , Tang Zhihui , Han Xuefeng
Published: October 2022

Background:

Botulinum toxin type A is an easy and efficacious treatment for gingival smile. However, the optimal dose and injection site are controversial.

Objective:

We compared the reduction in gingival exposure using two methods with different doses and injection sites.

Methods:

In this prospective self-controlled study, healthy participants with gingival smile (anterior gingival exposure of >3 mm) underwent two treatment methods. First, participants received a single-point injection of 2 U botulinum toxin type A per side (simplified method). After 8 months, the individualized method was performed with 2–5 U of botulinum toxin type A (total 4–10 U), which was injected at 1–2 sites according to pretreatment severity. Data were collected at baseline and at 4, 12, and 32 weeks of follow up.

Results:

Fifty-five participants were enrolled. Anterior gingival exposure and bilateral posterior gingival exposure were significantly reduced 4 and 12 weeks after botulinum toxin type A injection (P ≤ 0.05) with both methods. These parameters returned to baseline by 32 weeks (P > 0.05). Posttreatment anterior gingival exposure at 4 weeks and 12 weeks with the individualized method was significantly lower compared with the simplified method (both P ≤ 0.05). Patient satisfaction with the individualized method was preferred compared with the simplified method (P ≤ 0.05). Few adverse events were observed with both methods without statistical significance.

Conclusions:

It is necessary to increase the injection dose and tailor the injection site according to the pretreatment severity of anterior gingival smile.
Silicone Breast Implant Surface Texture Impacts Gene Expression in Periprosthetic Fibrous Capsules
Authors: Daneshgaran Giulia , Gardner Daniel J. , Chen Hsuan-Hsiu Annie , Niknam-Bienia Solmaz , Soundarajan Vinaya , Raghuram Anjali C. , Kim Gene H. , Labaj Pawel , Kreil David P. , Wang Charles , Hong Young-Kwon , Wong Alex K.
Published: October 2022

Purpose:

Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, while textured implants have been linked to the development of breast implant-associated ALCL. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, we can gain insight into the development of breast implant-associated pathologies.

Methods:

Miniature smooth or textured silicone implants were surgically inserted into female rats (n=10) and harvested for the surrounding capsules on postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture.

Results:

Out of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 (MMP3), troponin-T3 (TNNT3) and neuregulin-1 (NRG1). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was upregulated while NRG1 was downregulated compared to smooth capsules (mean relative fold change: 8.79, p=0.0059; 4.81, p=0.0056; 0.40, p<0.0001, respectively). Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules.

Conclusion:

An expression pattern of low MMP3/low TNNT3/high NRG1 is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. Our clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated pathologies.
H-wing Neoumbilicoplasty: A New Technique for Advanced Abdominoplasty and Umbilical Zones by Gender
Authors: Hoyos Alfredo E. , Perez Mauricio E. , Mogollon Ivan R. , Arcila Andres
Published: October 2022

BACKGROUND:

Multiple umbilicoplasty techniques have been described, even more after the advent of full tummy tuck procedures and the neo-umbilicoplasty (X-shaped incision) described by the authors in a previous report. However, we decided to upgrade the technique (H-wing incision) due to the former procedure relatively common complications.

PURPOSE:

We are reporting a case series of an upgraded technique for neo-umbilicoplasty (H-wing technique) and compared its outcomes with our previous standard procedure (X-Shaped).

METHODS:

We reviewed our records for neoumbilicoplasties performed between January 2014 and December 2019. We divided the procedures according to the surgical technique and performed a detailed analysis about timing, complications, uses and quality standards according to the patients’ opinion through a non-standardized survey.

RESULTS:

We found a total of 407 procedures distributed in two techniques: X-shaped (n=179) incision and H-wing technique (n=228). The former was performed from Jan 2014 to October 2016 and the Latter from September 2016 to December 2019. High Satisfaction indexes were found for both procedures, however less complications were seen in the H-wing group. The X-Shaped incision is thought to generate a greater force of tension over the flaps compared to that from H-wing technique, which consequently increased the risk of flap necrosis and flattening.

CONCLUSIONS:

The H-wing technique for neoumbilicoplasty decreases the risk of postoperative complications such as dehiscence, skin necrosis and navel flattening, while keeping high aesthetic standards and satisfaction indexes among patients. The technique can be used either after lipoabdominoplasty or secondary procedures as well.
The Interaction of HIV With Mental Health in the Modern Antiretroviral Therapy Era
Authors: Carrico Adam W. , Rubin Leah H. , Paul Robert H.
Published: October 2022

People with HIV (PWH) receiving effective antiretroviral therapy (ART) continue to display residual immune dysregulation that amplifies the risk for neuropsychiatric comorbidities. At the same time, PWH commonly experience intersectional stigma and other psychosocial stressors that are linked to neuroendocrine stress responses, potentiate residual immune dysregulation, and alter other biobehavioral processes relevant to health outcomes. This special issue of Psychosomatic Medicine seeks to advance our understanding of the intersection of HIV with mental health in the modern ART era. Several articles cover topics related to the prevalence and treatment of psychiatric comorbidities among PWH such as depression, suicidality, and substance use disorders. Other articles delineate biobehavioral mechanisms relevant to mental health in PWH such as inflammation, immune activation, neuroendocrine signaling, cellular aging, the microbiome-gut-brain axis, and neurobehavioral processes. Collectively, the articles in this special issue highlight the continued importance of biobehavioral and neurobehavioral mental health research in the modern ART era.
Predicting Treatment Response in Primary Aldosteronism Using 11C-Metomidate Positron Emission Tomography
Authors: Lu Ching-Chu , Chen Chien-Jung , Peng Kang-Yung , Chueh Jeff S. , Chang Chin-Chen , Yen Ruoh-Fang , Wu Vin-Cent ,   Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
Published: October 2022

Background

Appropriate treatment of primary aldosteronism (PA) depends on accurate lateralization. 11C-metomidate (MTO) is a tracer used in PET that provides functional information about the adrenal cortex. We aimed to perform MTO PET for patients with PA who are managed according to the guideline and to verify its correlation with other lateralization modalities and usefulness in outcome prediction.

Methods

Seventeen patients with PA who underwent MTO PET and had ≥1 lateralization modality (adrenal venous sampling and/or NP-59 adrenal scintigraphy) were included. SUVmax of each adrenal gland (higher uptake side, HSUVmax; lower uptake side, LSUVmax) and the ratio of HSUVmax to LSUVmax (contrast) were compared with lateralization modalities, postsurgical outcomes, and medical treatment outcomes. Cutoff values were used as outcome predictors.

Results

HSUVmax and LSUVmax increased in the order of bilateral, unilateral, and negative findings of CT, with opposite order of contrast. High discordant rate between MTO PET and other lateralization modalities was noted. Biochemical responders (n = 8) had significantly lower HSUVmax and LSUVmax than nonresponders, and clinical responders (n = 6) had borderline lower HSUVmax than nonresponders. By optimal cutoff values of HSUVmax and LSUVmax, MTO PET was able to predict biochemical and clinical outcomes in patients with medical treatment.

Conclusion

According to adrenal CT findings, MTO PET presented different uptake patterns. Patients with PA under medical treatment showed significantly lower tracer uptake in responders. Thus, MTO PET may be a useful imaging biomarker to predict medical treatment outcome. Multicenter prospective study with a larger number of patients is needed for further validation.
Systematic Review and Meta-analysis of the Additional Benefit of Pharmacological Thromboprophylaxis for Endovenous Varicose Vein Interventions
Authors: Turner Benedict R. H. , Machin Matthew , Jasionowska Sara , Salim Safa , Onida Sarah , Shalhoub Joseph , Davies Alun H.
Published: October 2022

Objective:

The primary objective of this systematic review and meta-analysis was to elucidate the rate of venous thromboembolism (VTE) after endovenous interventions for varicose veins in the presence of pharmacological and mechanical thromboprophylaxis versus mechanical thromboprophylaxis alone.

Background:

The VTE rate after endovenous procedures for varicose veins is higher than other day-case procedures and could be reduced with pharmacological thromboprophylaxis.

Methods:

The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines with a registered protocol (PROSPERO: CRD42021274963). Studies of endovenous intervention for superficial venous incompetence reporting the predefined outcomes with at least 30 patients were eligible. Data were pooled with a fixed effects model.

Results:

There were 221 trials included in the review (47 randomized trial arms, 105 prospective cohort studies, and 69 retrospective studies). In randomized trial arms, the rate of deep venous thrombosis with additional pharmacological thromboprophylaxis was 0.52% (95% CI, 0.23%–1.19%) (9 studies, 1095 patients, 2 events) versus 2.26% (95% CI, 1.81%–2.82%) (38 studies, 6951 patients, 69 events) with mechanical thromboprophylaxis alone. The rate of pulmonary embolism in randomized trial arms with additional pharmacological thromboprophylaxis was 0.45% (95% CI, 0.09–2.35) (5 studies, 460 participants, 1 event) versus 0.23% (95% CI, 0.1%–0.52%) (28 studies, 4834 participants, 3 events) for mechanical measures alone. The rate of EHIT grade III to IV was 0.35% (95% CI, 0.09–1.40) versus 0.88% (95% CI, 0.28%–2.70%). There was 1 VTE-related mortality and 1 instance of major bleeding, with low rates of minor bleeding.

Conclusions:

There is a significant reduction in the rate of DVT with additional pharmacological thromboprophylaxis and routine prescription of anticoagulation after endovenous varicose vein intervention should be considered. VTE risk for individual study participants is heterogeneous and risk stratification in future randomized interventional studies is critical to establish the clinical effectiveness and safety of additional pharmacological thromboprophylaxis.
Liver Transplant Outcomes in Patients With Postcapillary Pulmonary Hypertension
Authors: Kleb Cerise , Aggarwal Manik , Tonelli Adriano R. , White Mattie , Lyu Ruishen , Quintini Cristiano , Hashimoto Koji , Miller Charles , Cywinski Jacek , Eghtesad Bijan , Fares Maan , Menon K. V. Narayanan
Published: October 2022

Background.

Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH.

Methods.

This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH.

Results.

Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03).

Conclusions.

Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.
Enhanced STAT5a activation rewires exhausted CD8 T cells during chronic stimulation to acquire a hybrid durable effector like state
Authors: Beltra Jean-Christophe , Abdel-Hakeem Mohamed S. , Manne Sasikanth , Zhang Zhen , Huang Hua , Kurachi Makoto , Su Leon , Picton Lora , Muroyama Yuki , Casella Valentina , Huang Yinghui J. , Giles Josephine R. , Mathew Divij , Belman Jonathan , Klapholz Max , Decaluwe Hélène , Huang Alexander C. , Berger Shelley L. , Garcia K. Christopher , Wherry E. John
Published: October 2022

Rewiring exhausted CD8 T cells (TEX) towards more functional states is a major goal of cancer immunotherapy but has proven challenging due to the epigenetic stability of TEX. Indeed, TEX are epigenetically programmed by the transcription factor Tox. However, epigenetic changes continue to occur as TEX transition from progenitor (TEXprog), to intermediate (TEXint) and terminal (TEXterm) subsets, suggesting potential developmental flexibility in mature TEX subsets. By examining the transition of TEXprog into TEXint cells, we discovered a reciprocally antagonistic circuit between Stat5a and Tox in TEX cells. Stat5-activity controlled TEXint development, antagonized Tox, and instigated partial effector biology. Stat5 was also essential for TEX reinvigoration by PD-1 blockade. Indeed, temporal induction of Stat5-activity in TEX using an orthogonal IL-2/IL2Rβ-pair fostered TEXint cell accumulation and synergized with PD-L1 blockade. Constitutive Stat5a activity (STAT5CA) antagonized Tox-dependent TEX epigenetic programming to generate a durable hybrid effector/NK-like population with enhanced tumor control. Finally, enforcing Stat5-signals in established TEXprog partially rewired the TEX epigenetic landscape towards the effector/memory lineage. Together, these data highlight therapeutic opportunities of manipulating Stat5 to rewire TEX towards a durably protective hybrid program.
Aerosolizable plasmid DNA dry powders engineered by thin-film freezing
Authors: Xu Haiyue , Moon Chaeho , Sahakijpijarn Sawittree , Dao Huy M. , Alzhrani Riyad F. , Wang Jie-liang , Williams Robert O. , Cui Zhengrong
Published: October 2022

This study was designed to test the feasibility of using thin-film freezing (TFF) to prepare aerosolizable dry powders of plasmid DNA (pDNA) for pulmonary delivery. Dry powders of pDNA formulated with mannitol/leucine (70/30, w/w) at various of drug loadings, solid contents, and solvents were prepared using TFF, their aerosol properties (i.e., mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF)) determined, and selected powders were used for further characterization. Of the nine dry powders prepared, their MMAD values were about 1-2 mm, with FPF values (delivered) of 40-80%. The aerosol properties of the powders were inversely correlated with the pDNA loading and the solid content in the pDNA solution before thin-film freezing. Powders prepared with Tris-EDTA (TE) buffer or cosolvents (i.e., 1,4 dioxane or t-butanol in water), instead of water, showed slightly reduced aerosol properties. Ultimately, powders prepared with pDNA loading at 5% (w/w), 0.25% of solid content, with or without TE were selected for further characterization due to their overall good aerosol performance. The pDNA powders exhibited a porous matrix, crystalline structure, with a moisture content of <2% (w/w). Agarose gel electrophoresis confirmed the chemical integrity of the pDNA after it was subjected to TFF and after the TFF powder was actuated. A cell transfection study confirmed the activity of the pDNA after it was subjected to TFF. In conclusion, it is feasible to use TFF to produce aerosolizable pDNA dry powder for pulmonary delivery, while preserving the integrity and activity of the pDNA.
Feasibility of Using an Armband Optical Heart Rate Sensor in Naturalistic Environment
Authors: Yu Hang , Kotlyar Michael , Dufresne Sheena , Thuras Paul , Pakhomov Serguei
Published: October 2022

Consumer-grade heart rate (HR) sensors including chest straps, wrist-worn watches and rings have become very popular in recent years for tracking individual physiological state, training for sports and even measuring stress levels and emotional changes. While the majority of these consumer sensors are not medical devices, they can still offer insights for consumers and researchers if used correctly taking into account their limitations. Multiple previous studies have been done using a large variety of consumer sensors including Polar®devices, Apple®watches, and Fitbit®wrist bands. The vast majority of prior studies have been done in laboratory settings where collecting data is relatively straight-forward. However, using consumer sensors in naturalistic settings that present significant challenges, including noise artefacts and missing data, has not been as extensively investigated. Additionally, the majority of prior studies focused on wrist-worn optical HR sensors. Arm-worn sensors have not been extensively investigated either. In the present study, we validate HR measurements obtained with an arm-worn optical sensor (Polar OH1) against those obtained with a chest-strap electrical sensor (Polar H10) from 16 participants over a 2-week study period in naturalistic settings. We also investigated the impact of physical activity measured with 3-D accelerometers embedded in the H10 chest strap and OH1 armband sensors on the agreement between the two sensors. Overall, we find that the arm-worn optical Polar OH1 sensor provides a good estimate of HR (Pearson r = 0.90, p <0.01). Filtering the signal that corresponds to physical activity further improves the HR estimates but only slightly (Pearson r = 0.91, p <0.01). Based on these preliminary findings, we conclude that the arm-worn Polar OH1 sensor provides usable HR measurements in daily living conditions, with some caveats discussed in the paper.
Quantifying noise modulation from coupling of stochastic expression to cellular growth: An analytical approach
Authors: Zabaikina Iryna , Zhang Zhanhao , Nieto César , Bokes Pavol , Singh Abhyudai
Published: October 2022

The overexpression of many proteins can often have a detrimental impact on cellular growth. This expression-growth coupling leads to positive feedback - any increase of intracellular protein concentration reduces the growth rate of cell size expansion that in turn enhances the concentration via reduced dilution. We investigate how such feedback amplifies intrinsic stochasticity in gene expression to drive a skewed distribution of the protein concentration. Our results provide an exact solution to this distribution by analytically solving the Chapman-Kolmogorov equation, and we use it to quantify the enhancement of noise/skewness as a function of expression-growth coupling. This analysis has important implications for the expression of stress factors, where high levels provide protection from stress, but come at the cost of reduced cellular proliferation. Finally, we connect these analytical results to the case of an actively degraded gene product, where the degradation machinery is working close to saturation.
EXPOSURE TO GLYPHOSATE OR ROUNDUP™ DURING ZEBRAFISH EMBRYOGENESIS DIFFERENTIALLY AFFECTS METABOLISM AND SWIMMING BEHAVIOURS
Authors: Lacroix Rachel , Ibhazehiebo Kingsley , Kaushik Gaurav , Kurrasch Deborah Marie
Published: October 2022

Glyphosate-based herbicides (GBHs), the most recognized of which is Roundup™, are the most extensively used herbicides worldwide. GBHs were initially considered safe for animals since the primary target of the active ingredient, glyphosate, is only found in plants. Recent studies show that glyphosate can affect a range of animal physiologies; however, it remains poorly characterized as to whether animal GBH effects are mediated by glyphosate itself or are in response to toxic effects of the adjuvants and surfactants found in GBH formulations. Here we expose embryonic zebrafish to environmentally relevant doses of glyphosate or Roundup™ and compare effects on two systems in the larvae: cellular bioenergetics, since glyphosate can affect mitochondrial function, and behaviour, as a systems-level readout of lasting developmental changes. We showed that exposure of embryonic zebrafish to low levels of glyphosate resulted in decreased mitochondrially-mediated basal respiration and hypoactive swimming behavior in larval stage, whereas exposure to Roundup™ in this same treatment paradigm had the opposite effect, causing increased cellular respiration and increased locomotion. In addition, we also explored generational effects of F1 embryonic glyphosate or Roundup™ exposure in the F2, and showed that offspring born to zebrafish exposed to low-level glyphosate or Roundup™ during embryogenesis both exhibited reduced mitochondrially-mediated basal respiration and altered locomotion. Combined, these data show that embryonic exposure to glyphosate or the full formulation of GBHs caused differential effects on mitochondrial function and behaviours in vertebrates, with potential lasting effects on future generations.
Figure 1.

Graphical abstract.

Zebrafish (F1 generation) were exposed to glyphosate or Roundup™ from zero to 48 hours, with behaviour and mitochondrial bioenergetics assessed at larval timepoints (2- and 5-dpf). Offspring of glyphosate and Roundup™ exposed fish (F2 generation) behaviour and mitochondrial bioenergetics were assessed to the same paradigm as F1 fish at 5-dpf. Changes to core metabolic parameters and locomotion was observed in both F1 and F2 generations.
Oscillations and aperiodic activity: Evidence for dynamic changes in both during memory encoding
Authors: Preston Michael , Schaworonkow Natalie , Voytek Bradley
Published: October 2022

Electrical recordings of human brain activity via electroencephalography (EEG) show prominent, rhythmic voltage fluctuations. These periodic oscillations have been linked to nearly every cognitive and perceptual process, as well numerous disease states. Recent methodological and theoretical advances, however, have given rise to evidence for a functional role for non-oscillatory, aperiodic neural activity. Physiologically, this aperiodic activity has been linked to the relative contributions of neuronal excitatory and inhibitory signaling. Most importantly, however, traditional data analysis methods often conflate oscillations and aperiodic activity, masking the potentially separate roles these processes play in perception, cognition, and disease. Here we present a reanalysis of intracranial human EEG recordings from Fellner et al., 2019, using new methods for separately parameterizing oscillations and aperiodic activity in a time-resolved manner. We find that human memory encoding is not related to just oscillations or aperiodic activity, but rather that both processes are rapidly co-modulated during memory encoding. These results provide strong evidence for event-related dynamics of aperiodic and oscillatory activity in human memory, paving the way for future investigations into the unique functional roles of these two independent, but linked, processes in human cognition.
FANGORN: A quality-checked and publicly available database of full-length 16S-ITS-23S rRNA operon sequences
Authors: Walsh Calum J. , Srinivas Meghana , van Sinderen Douwe , Cotter Paul D. , Kenny John G.
Published: October 2022

Sequence comparison of 16S rRNA PCR amplicons is an established approach to taxonomically identify bacterial isolates and profile complex microbial communities. One potential application of recent advances in long-read sequencing technologies is to sequence entire rRNA operons and capture significantly more phylogenetic information than sequencing of the 16S rRNA (or regions thereof) alone, with the potential to increase the proportion of amplicons that can be reliably classified to lower taxonomic ranks. Here we describe FANGORN (Full-length Amplicons for the Next Generation Of rRNa analysis), a publicly available database of quality-checked 16S-ITS-23S rRNA operons, accompanied by multiple taxonomic classifications. FANGORN will aid researchers in analysis of their data and act as a standardised database to allow comparison of results between studies.
Scalable early detection of grapevine virus infection with airborne imaging spectroscopy
Authors: Romero Galvan Fernando E. , Pavlick Ryan , Trolley Graham , Aggarwal Somil , Sousa Daniel , Starr Charles , Forrestel Elisabeth , Bolton Stephanie , del Mar Alsina Maria , Dokoozlian Nick , Gold Kaitlin M.
Published: October 2022

Viral diseases, including Grapevine Leafroll-associated Virus Complex 3 (GLRaV-3), cause $3 billion in damages and losses to the United States wine and grape industry annually. GLRaV-3 has a well-studied, year-long latent period in which vines are infectious but do not yet display visible symptoms, making it an ideal model pathosystem to evaluate the scalability of symptomatic and asymptomatic imaging spectroscopy-based disease detection. Plant disease causes physiological and chemical changes to occur locally and systemically throughout a plant, which imaging spectroscopy can detect both directly and indirectly. Reliable and scalable disease detection during the latent period would greatly reduce management costs, as current detection methods are entirely ground-based, labor-intensive, and expensive. Here, we use data collected in September 2020 by the NASA Airborne Visible/Infrared Imaging Spectrometer Next Generation (AVIRIS-NG) to detect GLRaV-3 in Cabernet Sauvignon grapevines in Lodi, CA. During September 2020 and 2021, industry collaborators scouted 317 acres of Vitis vinifera winegrapes for visible disease symptoms, and collected a subset for confirmation molecular testing at a commercial facility. Grapevines identified as visibly diseased in 2021 were assumed to have been latently infected (asymptomatic) during the September 2020 AVIRIS-NG data collection. We combined random forest with synthetic minority oversampling technique (SMOTE) to train multiple spectral models able to distinguish between non-infected (NI) and GLRaV-3-infected grapevines. We observed clear spectral differences that allowed for differentiation between NI and GLRaV-3 infected vines both pre- and post-symptomatically at 1m through 5m resolution. Our two best performing models had 87% accuracy (0.73 Kappa) distinguishing between NI and asymptomatic (aSy), and 85% accuracy (0.71 Kappa) distinguishing between NI and (aSy + symptomatic [Sy]) respectively. We hypothesize these spectral differences are linked to changes in overall plant physiology induced by disease, as visible foliar symptoms were restricted to the lower canopy.

Highlights

Airborne imaging spectroscopy allows for scalable early-detection models of grapevine leafroll-associated virus complex 3 (GLRaV-3).

Random Forest based models trained with scouting ground data and imaging spectroscopy are accurate up to 5 meter but perform best at 3 meter spatial resolution.

GLRaV-3 detection via imaging spectroscopy will not replace existing field scouting strategies or molecular testing but supplement by allowing for more strategic resource deployment to improve the overall financial, environmental, and societal sustainability of winegrape production.
Serotonergic Modulation of Spinal Circuitry Restores Motor Function after Chronic Spinal Cord Injury
Authors: Walvekar Sarita , Robinson Robert B. , Chadwick Hailey M. , Burch Rebecca M. , Ding Hanzhang , Perlmutter Steve I. , Moorjani Samira
Published: October 2022

Electrical stimulation of the nervous system has been employed to enhance the recovery of motor function produced by use-dependent rehabilitation, which is the current gold standard of treatment, following spinal cord injury. However, the therapeutic effects almost always rely on the sustained activation of muscles or neurons, making the benefits largely contingent on continued delivery of stimulation. In the present study, we describe a neuromodulatory intervention that combined intraspinal delivery of serotonergic agonists with use-dependent rehabilitation to restore motor function after a chronic moderate-to-severe cervical contusion in rats that produces impairments in upper-limb movements and dexterity. We show that targeted delivery of quipazine, a broad-spectrum serotonergic agonist, caudal to the lesion increased the effectiveness of physical rehabilitation, leading to substantially improved motor-recovery outcomes in severely-injured, but not moderately-injured, animals. Delivery of quipazine significantly augmented recovery of skilled reach and grasp movements after a severe injury, but moderately-injured animals received no additional benefit from quipazine over physical rehabilitation alone. This difference was perhaps due to a greater loss of serotonin after a severe injury and a resulting environment in which exogenously-applied serotonin can improve circuit function. Our experiments highlight an important role for serotonin in restoration of motor function that is dependent on the severity of the spinal cord injury. They also allude to a potential role for residual serotonin as a biomarker of injury severity. Remarkably, quipazine-mediated behavioral improvements persisted for weeks after termination of neuromodulator delivery, signaling repair of severely-damaged adult spinal circuitry that drives lasting motor recovery.

Significance Statement

We describe a neuromodulatory intervention that combined intraspinal delivery of serotonergic agonists with use-dependent physical rehabilitation, which is the current standard of treatment, to promote motor recovery after a chronic moderate-to-severe spinal-contusion injury. Our results show that targeted delivery of serotonergic agonists caudal to the lesion increased the effectiveness of use-dependent rehabilitation, leading to substantially improved motor-recovery outcomes in severely-injured, but not moderately-injured, animals. Notably, therapeutic gains persisted for weeks after termination of neuromodulator delivery—a finding that is both unique and clinically relevant—signaling plasticity induction and repair in chronically-damaged adult spinal circuitry. Our experiments provide important insights into serotonergic modulation of spinal circuitry and highlight a potential role for residual serotonin as a neurochemical biomarker of injury severity.
Wavelet-based Approach for Diagnosing Attention Deficit Hyperactivity Disorder (ADHD)
Authors: Vimalajeewa Dixon , McDonald Ethan , Bruce Scott Alan , Vidakovic Brani
Published: October 2022

Attention deficit hyperactivity disorder (ADHD) is a common cognitive disorder affecting children. ADHD can interfere with educational, social, and emotional development, so early detection is essential for obtaining proper care. Standard ADHD diagnostic protocols rely heavily on subjective assessments of perceived behavior. An objective diagnostic measure would be a welcome development and potentially aid in accurately and efficiently diagnosing ADHD. Analysis of pupillary dynamics has been proposed as a promising alternative method of detecting affected individuals effectively. This study proposes a method based on the self-similarity of pupillary dynamics and assesses its strength as a potential diagnostic biomarker. Localized discriminatory features are developed in the wavelet domain and selected via a rolling window method to build classifiers. The application on a task-based pupil diameter time series dataset of children aged 10-12 years shows that the proposed method achieves greater than 78% accuracy in detecting ADHD. Comparing with a recent approach that constructs features in the original data domain, the proposed wavelet-based classifier achieves more accurate ADHD classification with fewer features. The findings suggest that the proposed diagnostic procedure involving interpretable wavelet-based self-similarity features of pupil diameter data can potentially aid in improving the efficacy of ADHD diagnosis.
Distinct Heterogeneity in the Naive T cell Compartments of Children and Adults
Authors: Gustafson Claire E. , Thomson Zachary , He Ziyuan , Swanson Elliott , Henderson Katherine , Pebworth Mark-Phillip , Okada Lauren Y. , Heubeck Alexander T. , Roll Charles R. , Hernandez Veronica , Weiss Morgan , Genge Palak C. , Reading Julian , Giles Josephine R. , Manne Sasikanth , Dougherty Jeanette , Jasen CJ , Greenplate Allison R. , Becker Lynne A. , Graybuck Lucas T. , Vasaikar Suhas V. , Szeto Gregory L. , Savage Adam K. , Speake Cate , Buckner Jane H. , Li Xiao-jun , Torgerson Troy R. , Wherry E. John , Bumol Thomas F. , Vella Laura A. , Henrickson Sarah E. , Skene Peter J.
Published: October 2022

The naive T cell compartment undergoes multiple changes across age that associate with altered susceptibility to infection and autoimmunity. In addition to the acquisition of naive-like memory T cell subsets, mouse studies describe substantial molecular reprogramming of the naive compartment in adults compared with adolescents. However, these alterations are not well delineated in human aging. Using a new trimodal single cell technology (TEA-seq), we discovered that the composition and transcriptional and epigenetic programming of the naive T cell compartment in children (11-13 yrs) is distinct from that of older adults (55-65 yrs). Naive CD4 T cells, previously considered relatively resistant to aging, exhibited far more pronounced molecular reprogramming than naive CD8 T cells, in which alterations are preferentially driven by shifts in naive-like memory subsets. These data reveal the complex nature of the naive T cell compartment that may contribute to differential immune responses across the spectrum of human age.

One Sentence Summary:

The naive CD8 and CD4 T cell compartments in humans are heterogeneous and impacted differently with age, in which naive CD8 T cell subsets dramatically shift in composition and true naive CD4 T cells display significant molecular re-programming.
Surgical procedure for implantation of Opto-Array in nonhuman primates
Authors: Azadi Reza , Bohn Simon , Eldridge Mark A. G. , Afraz Arash
Published: October 2022

Optogenetics allows precise temporal control of neuronal activity in the brain. Engineered viral vectors are routinely used to transduce neurons with light-sensitive opsins. However, reliable virus injection and light delivery in animals with large brains, such as nonhuman primates, has proven challenging. The Opto-Array is a novel yet simple device that is used to deliver light to extended regions of surface cortex for high-throughput behavioral optogenetics in large brains. Here we present protocols for surgical delivery of virus and implantation of the Opto-Array in two separate surgeries in a rhesus monkey’s inferior temporal cortex. As a proof of concept, we measured the behavioral performance of an animal detecting cortical optogenetic stimulations with different illumination power and duration using the Opto-Array. The animal was able to detect the optogenetic stimulation for all tested illumination powers and durations. A regression analysis also showed both power and duration of illumination significantly modulate the detectability of the optogenetic stimulation. The outcome of this approach is superior to the standard practice of injecting and recording through a chamber for large areas of surface cortex. Moreover, the chronic nature of the Opto-Array allows perturbation of neuronal activity of the same site across multiple sessions because it is highly stable, thus data can be pooled over months. The detailed surgical method presented here makes it possible to use optogenetics to modulate neuronal activity across large regions of surface cortex in the nonhuman primate brain.
Cortical Contributions to Medial Frontal β-Bursts during Executive Control
Authors: Errington Steven P. , Westerberg Jacob A. , Woodman Geoffrey F. , Schall Jeffrey D.
Published: October 2022

EEG β-bursts observed over the medial frontal cortex are claimed to mediate response inhibition despite their infrequent occurrence. The weak association with stopping behavior is supposed to be a by-product of the low signal-to-noise ratio of EEG recordings. We tested the premise that β-bursts are more common within the cerebral cortex and more directly associated with response inhibition. We sampled simultaneously EEG and intracortical local field potentials (LFP) within the medial frontal cortex (MFC) of two macaque monkeys performing a response inhibition task. Intracortical β-bursts were just as infrequent as those in EEG and did not parallel the likelihood of canceling a planned response. Cortical β-bursts were more prevalent in upper layers but were not synchronized across a cortical column or with EEG β-bursts. These findings contradict claims for a causal contribution of β-bursts during response inhibition, provide important constraints for biophysical and cortical circuit models, and invite further considerations of β-burst function in cognitive control.
A hybrid reconstruction of the physical model with the deep-learning that improves structured illumination microscopy
Authors: Wang Jianyong , Fan Junchao , Zhou Bo , Huang Xiaoshuai , Chen Liangyi
Published: October 2022

In handling raw images with low signal-to-noise (SNR) ratios, conventional algorithms of structured illumination microscopy are prone to artifacts, while deep-learning-based (DL) algorithms may lead to degradation and hallucinations. We propose a hybrid that combines the physical inversion model with a Total Deep Variation regularization. In super-resolving from low SNR images such as actin filaments, our method outperforms conventional or DL methods in suppressing artifacts and hallucinations while maintaining resolutions.
Circular RNAs arising from synaptic host genes are modulated by SFPQ RNA-binding protein and increased during human neuronal differentiation
Authors: Watts Michelle , Oksanen Marika , Lejerkrans Sanna , Mastropasqua Francesca , Gorospe Myriam , Tammimies Kristiina
Published: October 2022

Background

Circular RNAs (circRNAs) are emerging as a key component of the complex neural transcriptome implicated in brain development. However, the specific expression patterns and functions of circRNAs in human neuronal differentiation have not been explored.

Results

Using total RNA sequencing analysis, we identified expressed circRNAs during the differentiation of human neuroepithelial stem (NES) cells into developing neurons and discovered that many circRNAs originated from host genes associated with synaptic function. Interestingly, when assessing population data, exons giving rise to circRNAs in our dataset had a higher frequency of genetic variants. Additionally, screening for RNA-binding protein sites identified enrichment of Splicing Factor Proline and Glutamine Rich (SFPQ) motifs in increased circRNAs, several of which were reduced by SFPQ knockdown and enriched in SFPQ ribonucleoprotein complexes.

Conclusions

Our study provides an in-depth characterisation of circRNAs in a human neuronal differentiation model and highlights SFPQ as both a regulator and binding partner of circRNAs elevated during neuronal maturation.