bluuebunny/crossref_metadata_2025 huggingface dataset:
Nevi – when to refer
Authors: Shah Saloni A. , Jahnke Marla N.
Published: July 2024

Purpose of review

Congenital melanocytic nevi (CMN) and acquired nevi are prevalent in pediatric populations, with distinct characteristics and management considerations. This chapter aims to equip pediatricians with knowledge to discern between benign and high-risk nevi, facilitating appropriate referrals and management within primary care settings. Risk factors associated with malignant melanoma (MM) underscore the importance of vigilant monitoring and early referral to dermatology for suspicious lesions.

Recent findings

Recent findings highlight the variability in CMN presentation and the evolving diagnostic strategies, emphasizing the need for multidisciplinary approaches to optimize patient outcomes.

Management of CMN involves tailored surveillance and intervention strategies, with an emphasis on early identification of high-risk features for MM and neurocutaneous melanosis (NCM). Pediatricians play a crucial role in advocating for sun protection practices and facilitating timely referrals, thereby contributing to the overall well being of pediatric patients with nevi.
Management of Extracorporeal Membrane Oxygenation Anticoagulation in the Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference
Authors: Willems Ariane , Anders Marc M. , Garcia Alejandro V. , Vogel Adam M. , Yates Andrew R. , Muszynski Jennifer A. , Alexander Peta M.A. , Steffen Katherine , Emani Sitaram , Gehred Alison , Lyman Elizabeth , Raman Lakshmi ,   for the Pediatric Extracorporeal Membrane Oxygenation [ECMO] Anticoagulation CollaborativE (PEACE), in collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the Pediatric Critical Care Blood Research Network (BloodNet), and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Published: July 2024

OBJECTIVES:

To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference.

DATA SOURCES:

A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION:

ECMO anticoagulation and hemostasis management in the perioperative period and during procedures.

DATA EXTRACTION:

Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS:

Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Four good practice statements, 7 recommendations, and 18 consensus statements are presented.

CONCLUSIONS:

Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.
Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference
Authors: Moynihan Katie M. , Ryerson Lindsay M. , Le Jennifer , Nicol Kathleen , Watt Kevin , Gadepalli Samir K. , Alexander Peta M.A. , Muszynski Jennifer A. , Gehred Alison , Lyman Elizabeth , Steiner Marie E. ,   for the Pediatric Extracorporeal Membrane Oxygenation (ECMO) Anticoagulation CollaborativE (PEACE), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Published: July 2024

OBJECTIVES:

To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference.

DATA SOURCES:

A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION:

Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs).

DATA EXTRACTION:

Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.

MEASUREMENTS AND MAIN RESULTS:

Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented.

CONCLUSIONS:

Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.
Evaluating inflammatory outcomes: A systematic review and meta-analysis of aerobic versus resistance exercise interventions
Authors: Leonardo Sofia , Fregni Felipe
Published: July 2024

Chronic inflammation is widely recognized as a crucial contributor to the onset and progression of various diseases. Physical activity serves as a nonmedicinal intervention known to influence inflammatory dynamics. The specific effects of distinct exercise types, namely aerobic and resistance training, on inflammatory indices have not been fully delineated. This systematic review with meta-analysis seeks to clarify the relative impacts of these 2 forms of exercise on markers of inflammation. An exhaustive literature review was performed across several databases, including MEDLINE, EMBASE, and the Cochrane Library, to identify randomized controlled trials that assess the impact of aerobic versus resistance training on inflammatory markers. The primary variables of interest were alterations in inflammatory indicators such as C-reactive protein, interleukin-6, and tumor necrosis factor–alpha. We synthesized the data employing a random-effect meta-analytical approach and evaluated heterogeneity using the I² statistic. The literature search culminated in 36 randomized controlled trial with a collective participant count of 3616. Data analyses revealed that aerobic training is associated with a notable decrease in levels of interleukin-6 [standardized mean difference (SMD): −0.13, 95% CI: −0.31 to −0.05] and C-reactive protein (SMD: −0.28, 95% CI: −0.47 to −0.09), whereas resistance training is linked to a significant reduction in tumor necrosis factor–alpha levels (SMD: −0.61, 95% CI: −0.87 to −0.34). The investigation indicates that both aerobic and resistance training modalities play roles in diminishing inflammatory markers, likely through different biological processes. These insights highlight the critical nature of selecting appropriate exercise modalities to manage inflammatory health issues effectively. It is imperative to conduct further studies to unravel the precise mechanisms at play and to refine exercise recommendations for tailored management of inflammation.
Fecal microbiota transplantation in patients with spinal cord injury with recurrent Clostridioides difficile infection: a case report
Authors: Wong Samford , Forbes Alastair , Kenssous Noureddine , Naidoo Anitha
Published: July 2024

Objective:

Fecal microbiota transplantation (FMT) is an emerging treatment for Clostridioides difficile infection (CDI) through reconstruction of the gut microbiota, but its impact in people with spinal cord injury (PWSCI) is limited. The aim of this paper is to report the use of FMT in a PWSCI with CDI.

Methods:

The FMT was conducted on October 30, 2019.

Results:

A 72-year-old man with T8 complete paraplegia from compression of the spinal cord due to an epidural hematoma was referred. He has known severe pancreatic enzyme insufficiency, malabsorption, and a history of recurrent CDI. Despite intensive dietetic treatment (probiotics, enteral nutrition, and parenteral nutrition), and multiple courses of antibiotics (vancomycin and fidaxomicin at various doses and durations) for CDI, he continued to be CDI-positive. His CDI was successfully treated after 2 colonoscopically delivered FMTs. At the 24-month follow-up, he remains CDI-negative and reports improved independence. Although there has been considerable variability in the criteria for the FMT and its mode of delivery, FMT can be an option to treat recurrent CDI.

Conclusion:

This case report reports a PWSCI with recurrent CDI who has been successfully treated with FMT and remains in long-term remission. It supports the consideration of FMT in PWSCI with CDI when antibiotic treatment has been unsuccessful.
Prevalence of neck pain and associated risk factors among the private sector office employees in Bangladesh
Authors: Hossain Sayed Imran , Chowdhury Md. Omar Sharif Ahmmed , Nasrin Sumaiya , Khatun Most. Rumpa , Hossain Shohal
Published: July 2024

Background:

Globally, most people face several musculoskeletal problems, especially neck pain. Activities, work styles, and living standards of office employees in Bangladesh vary from place to place. Hence, our aim is to investigate the prevalence of neck pain and related risk factors in Bangladeshi private sector employees.

Methodology:

A sample was selected to assess neck pain prevalence and related risk factors among 384 private sector employees aged 21–60 years in Bangladesh. Regression analysis was performed on their socio-economic, neck pain, and associated risk factors information through interviews with questionnaires.

Results:

Data analysis shows that office employees have a relatively higher prevalence rate of cervical pain and it is 34.7%. In this study, we found the results of a logistic regression model to predict factors associated with neck pain. The results of this study indicated that individuals aged 40 years and above, with an OR of 6.148 (P = 0.046) and neck holding the forward bent posture for a prolonged time, were slightly significant to have neck pain (P<0.001).

Conclusions:

The neck pain prevalence was high among private sector office workers in Bangladesh and some associated neck pain factors were found in this study. The results of our investigation indicated that individuals with higher age, and neck holding position were slightly significant to have neck pain. These research findings also suggest scope for work strategies that can promote a positive work environment, such as short breaks at work and an ergonomic setting.
Evaluation of the Bilateral Symmetry Assumption in Manual Wheelchair Propulsion
Authors: Rum Lorenzo , Goosey-Tolfrey Vicky , Vegter Riemer , Bergamini Elena
Published: July 2024

This systematic review aimed to 1) verify bilateral symmetry assumption in manual wheelchair propulsion in daily life and sports, and its relationship with injury risk and sports performance, and 2) evaluate methods for assessing bilateral symmetry. Scopus, Web of Science, PubMed, and EBSCO databases were searched for articles published before January 2024 investigating bilateral symmetry in manual wheelchair users and/or healthy participants during manual wheelchair propulsion. Two independent reviewers screened, extracted data, and assessed methodological quality of retrieved papers. Twenty-five studies were included. In daily ground-level propulsion, minimal asymmetries were observed in kinematic, kinetic, and temporal parameters when averaging three or more push cycles. In the sports context, diverse findings emerged, ranging from up to 27% side-to-side differences in propulsion kinetics and kinematics during sprinting, to descriptions of both symmetrical and asymmetrical upper limb motions. Limited evidence exists regarding the role of asymmetry in manual wheelchair propulsion as a risk factor for injury and pain, as well as the association between sprinting performance and symmetry. In conclusion, bilateral symmetry assumption in manual wheelchair propulsion is valid only under specific conditions (i.e., slow/moderate speed, averaging ≥3 push cycles, smooth level ground). The wheeling environment and interindividual variability impact symmetry research outcome and require consideration in future studies.
Impact of methamphetamine use on HIV and other health outcomes at an urban HIV medicine clinic
Authors: Bamford Laura , Rajagopal Amutha , Grelotti David , Justice-Royster Vernay , Karim Afsana , Montoya Jessica
Published: July 2024

Background:

The methamphetamine epidemic threatens progress towards ending the HIV epidemic in the United States. Further characterizing the prevalence and impact of methamphetamine use among people with HIV (PWH) is necessary to inform integrated HIV and methamphetamine treatment strategies.

Methods:

We conducted a retrospective chart review to characterize methamphetamine use among 3092 PWH at an urban HIV Medicine clinic between July 1, 2022 and June 30, 2023. The chi-squared test was utilized to assess for statistically significant differences in demographics and HIV and other health outcomes among PWH who use and do not use methamphetamine.

Results:

The prevalence of methamphetamine use among PWH in this cohort was 17%. PWH who used methamphetamine were more likely to be <40 years of age, identify as White race, live in neighborhoods with low Healthy Places Index scores, identify as lesbian, gay, or bisexual, report male sex with men (MSM), MSM and injection drug use (IDU), or IDU as HIV transmission risk factor, miss scheduled HIV primary care visits, and screen positive for hepatitis C virus antibody, gonorrhea, chlamydia, and major depressive disorder. PWH who use methamphetamine were also less likely to be virally suppressed and have a CD4+ cell count ≥200 cells/mm3.

Conclusion:

Methamphetamine use is prevalent among PWH at this urban HIV Medicine Clinic and is associated with worse HIV and other health outcomes which likely increase the risk of HIV transmission. The integration of methamphetamine use disorder treatment into HIV primary care is necessary to work toward ending the syndemics of methamphetamine and HIV.
Two-Year Mortality Predictors in Fragility Fractures—A Medical Records Review Study
Authors: Azevedo Sofia Ferreira , Mazeda Carolina , Silva Susana Pinto , Barcelos Anabela
Published: July 2024

Purpose

To evaluate two-year mortality predictors in all subtypes of fragility fractures.

Methods

Medical records review, single-center study with Portuguese patients with fragility fractures; A univariate analysis, with chi-square for categorical variables and parametric t-student and non-parametric Wilcoxon tests for continuous variables, was performed. Posteriorly, a survival analysis, with subsequent Cox regression was conducted to establish independent risk factors/ predictors of two-year mortality in fragility fractures.

Results

758 patients were enrolled in the study. We found a total of 151 deaths within the first two years post-fracture. On Cox regression, older age [OR1.10 CI (1.05-1.11)], male sex [OR1.85 CI(1.24-2.75)], anemia at baseline [OR2.44 CI(1.67-3.57)], malignancy [OR4.68 CI (2.13-10.27)], and multimorbidity [OR1.78 CI(1.11-2.87)] were found as independent predictors for two-year post-fracture mortality.

Conclusion

Our study suggests that male sex, older age, anemia, malignancy, and multimorbidity are mortality predictors in the first two years after fragility fractures, reinforcing the importance of comorbidity management in preventing or, at least, minimizing adverse outcomes following fragility fractures.
Endovascular Embolization and Atorvastatin Therapy for Recurrent Chronic Subdural Hematoma
Authors: Lv Enzhen , Xue Xiaoli , Xu Zitao
Published: July 2024

Recurrent chronic subdural hematoma poses a significant clinical challenge. While craniotomy effectively removes the hematoma membrane, it is an invasive procedure associated with significant trauma. Recently, endovascular embolization of the middle meningeal artery has emerged as a promising minimally invasive alternative, demonstrating efficacy and a low recurrence rate in treating chronic subdural hematoma. Furthermore, postoperative administration of oral atorvastatin calcium may enhance hematoma absorption, thereby improving patient outcomes during the early recovery phase.
Feasibility of Home Collection for Urogenital Microbiome Samples
Authors: Lukacz Emily S. , Fok Cynthia S. , Bryant MacKenzie , Rodriguez-Ponciano Dulce P. , Meister Melanie R. , Mueller Margaret G. , Lewis Cora E. , Lowder Jerry L. , Smith Ariana L. , Stapleton Ann , Ayala Amy , Pakpahan Ratna , Hortsch Sarah , McDonald Daniel , Putnam Sara , Rudser Kyle , Song Se Jin , Knight Rob , Brubaker Linda ,   the PLUS Research Consortium
Published: July 2024

Importance

Feasibility of home urogenital microbiome specimen collection is unknown.

Objectives

This study aimed to evaluate successful sample collection rates from home and clinical research centers.

Study Design

Adult women participants enrolled in a multicentered cohort study were recruited to an in-person research center evaluation, including self-collected urogenital samples. A nested feasibility substudy evaluated home biospecimen collection prior to the scheduled in-person evaluation using a home collection kit with written instructions, sample collection supplies, and a Peezy™ urine collection device. Participants self-collected samples at home and shipped them to a central laboratory 1 day prior to and the day of the in-person evaluation. We defined successful collection as receipt of at least one urine specimen that was visibly viable for sequencing.

Results

Of 156 participants invited to the feasibility substudy, 134 were enrolled and sent collection kits with 89% (119/134) returning at least 1 home urine specimen; the laboratory determined that 79% (106/134) of these urine samples were visually viable for analysis. The laboratory received self-collected urine from the research center visit in 97% (115/119); 76% (91/119) were visually viable for sequencing. Among 401 women who did not participate in the feasibility home collection substudy, 98% (394/401) self-collected urine at the research center with 80% (321/401) returned and visibly viable for sequencing.

Conclusions

Home collection of urogenital microbiome samples for research is feasible, with comparable success to clinical research center collection. Sample size adjustment should plan for technical and logistical difficulties, regardless of specimen collection site.
Elongatibacter sediminis gen. nov., sp. nov., isolated from intertidal sediment, and genomic comparison with all genera in the family Wenzhouxiangellaceae
Authors: Zhang Xin-Yue , Ye Yu-Qi , Feng Yan-Jun , Gong Hong-Nan , Du Zong-Jun , Ye Meng-Qi
Published: July 2024

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3–0.6 µm and lengths of 2.0–11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).
Reduced Auditory Perception and Brain Response with Quiet TMS Coil
Authors: Murphy David L. K. , Koponen Lari M. , Wood Eleanor , Li Yiru , Bukhari-Parlakturk Noreen , Goetz Stefan M. , Peterchev Angel V.
Published: July 2024

BACKGROUND

Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC).

OBJECTIVE

To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil.

METHODS

Nine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120% RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal.

RESULTS

RMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100% coil-specific RMT sounded like Cool-B65 at 34% RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS-DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation.

CONCLUSIONS

The stimulation efficiency of qTMS-DCC matched Cool-B65, while having substantially lower perceived loudness and auditory-evoked potentials.

Highlights

qTMS coil is subjectively and objectively quieter than conventional Cool-B65 coil

qTMS coil at 100% motor threshold was as loud as Cool-B65 at 34% motor threshold

Attenuated coil noise reduced auditory N100 and P180 evoked response components

qTMS coil enables reduction of auditory activation without masking
HHV-6B, HHV-7, and B19V Are Frequently Found DNA Viruses in the Human Thymus but Show No Definitive Link with Myasthenia Gravis
Authors: Nowlan Kirsten , Hannolainen Leo , Assimakopoulou Irini M , Dürnsteiner Pia , Sarkkinen Joona , Suokas Santeri , Hedman Lea , Tienari Pentti J. , Hedman Klaus , Niku Mikael , Aaltonen Leena-Maija , Huuskanen Antti , Räsänen Jari , Ilonen Ilkka K , Mäyränpää Mikko I. , Dunkel Johannes , Laakso Sini M , Söderlund-Venermo Maria , Perdomo Maria F. , Kekäläinen Eliisa
Published: July 2024

Myasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies that target components of the neuromuscular junction, primarily the acetylcholine receptor (AChR), resulting in muscle weakness. The thymus plays a significant role in MG pathogenesis, particularly in patients under the age of 50, who display pathological alterations and possess elements conducive to autoimmune reactions. Although viral infections are suspected drivers of thymic pathogenesis, the exact aetiology of MG remains elusive. This study investigates the potential link between MG and DNA viruses within the thymus. Using targeted next-generation sequencing and quantitative PCR, we analysed the presence of human parvovirus B19 (B19V) and nine human herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6A, HHV-6B, HHV-7, and HHV-8) in fresh tissue samples from 19 non-thymomatous MG patients, 16 thymomas (3 with and 14 without MG), 41 normal thymus tissues, and 20 tonsils from healthy individuals. HHV-6B was the most common virus, found in over 50% of all tissue groups. B19V DNA was detected in 40% of adult control thymic tissue, 72% of MG thymus, 7.7% of non-MG thymoma, and 50% of tonsil samples. HHV-7 was present in 15-30% of thymus tissues and 95% of tonsils, while EBV was detected in less than 25% of all thymus samples but 85% of tonsils. In B19V seropositive individuals, B19V DNA was detected in 100% of thymic tissue from both MG patients and healthy individuals, except in thymomatous tissues, where it was found in only one of thirteen seropositive individuals. Immunohistochemistry for B19V protein expression did not show evident B19V VP1/VP2 protein expression, indicating dormant viral persistence. Laser capture microdissection (LCM) and RNAscope in situ hybridisation pinpointed B19V DNA localisation to the thymus medulla. This study is the first to demonstrate the persistence of various DNA viruses in the human thymus. However, neither B19V nor the nine human herpesviruses showed specific enrichment in MG thymic tissue compared to controls, suggesting that these viral infections are unlikely to be sole environmental triggers for MG.
Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area of posterior parietal cortex
Authors: Griggs Whitney S. , Norman Sumner L. , Tanter Mickael , Liu Charles , Christopoulos Vasileios , Shapiro Mikhail G. , Andersen Richard A.
Published: July 2024

The lateral intraparietal cortex (LIP) located within the posterior parietal cortex (PPC) is an important area for the transformation of spatial information into accurate saccadic eye movements. Despite extensive research, we do not fully understand the functional anatomy of intended movement directions within LIP. This is in part due to technical challenges. Electrophysiology recordings can only record from small regions of the PPC, while fMRI and other whole-brain techniques lack sufficient spatiotemporal resolution. Here, we use functional ultrasound imaging (fUSI), an emerging technique with high sensitivity, large spatial coverage, and good spatial resolution, to determine how movement direction is encoded across PPC. We used fUSI to record local changes in cerebral blood volume in PPC as two monkeys performed memory-guided saccades to targets throughout their visual field. We then analyzed the distribution of preferred directional response fields within each coronal plane of PPC. Many subregions within LIP demonstrated strong directional tuning that was consistent across several months to years. These mesoscopic maps revealed a highly heterogenous organization within LIP with many small patches of neighboring cortex encoding different directions. LIP had a rough topography where anterior LIP represented more contralateral upward movements and posterior LIP represented more contralateral downward movements. These results address two fundamental gaps in our understanding of LIP’s functional organization: the neighborhood organization of patches and the broader organization across LIP. These findings were achieved by tracking the same LIP populations across many months to years and developing mesoscopic maps of direction specificity previously unattainable with fMRI or electrophysiology methods.
Prognostic Significance of Potential Target Networks and P16INK4a In Early Diagnosis of Non-Small Cell Lung Cancer
Authors: Kundadka Varnika , Vatsa Radha , Kaur Navrinder
Published: July 2024

This study aimed to identify the prognostic signature of p16INK4a and related genes in non-small cell lung cancer (NSCLC). Since non-small cell lung cancer shows a poor prognosis, the 5-year survival rate in advanced stages is low. This emphasizes the need to identify more reliable diagnostic biomarkers for the early diagnosis of NSCLC and understand the molecular mechanisms underlying the progression of the disease. The role of P16 in essential cellular pathways are still unknown. Understanding its function and the mechanisms underlying its dysregulation could potentially lead to the development of targeted therapies for certain cancers. To address this, bioinformatics analyses revealed differential expression of genes in lung tumour tissues vs control samples. The interactions among the identified DEGs can help better understand the underlying molecular mechanism of NSCLC. We investigated the correlation between p16INK4a expression and genes involved in the relevant interactive pathways in early-stage NSCLC. These can serve as potential diagnostic and therapeutic biomarkers for NSCLC.
A smartphone-based genetically recombinant whole-cell biosensor for highly sensitive monitoring of polychlorinated biphenyls (PCBs)
Authors: Luo Qiangqiang , Zhang Faying , Zhang Mengjie , Hu Shantong , Li Xin , Pan Li , Lu Zhenghui , Wu Pan , Zhang Guimin
Published: July 2024

Polychlorinated biphenyls (PCBs) are highly carcinogenic and persistent pollutants commonly found in ecosystems. Their complex congeners pose a huge challenge to instrumental analysis and ELISA methods, which prefer single and known targets. To overcome this limitation, here we developed anEscherichia coliwhole-cell biosensor (WCB) for simultaneously detecting multiple PCB congeners. In this sensor, PCBs were firstly converted into hydroxylated PCBs (OH-PCBs) bybphABdegradation circuits, which then serve as high-affinity targets of transcriptional factor HbpRCBP6-based sensing pathways for sensitive response through extensive chassis screening. The resulting biosensor BL21(DE3)/HbpRCBP6-bphABshows the lowest detection limits for 2-CBP (2-chlorobiphenyl) to date and can recognize various PCB homologues, including 3-CBP, 4-CBP, 2,3-diCBP and 2,2’-diCBP, with detection limits of 0.06-1 μM. Further investigation of the docking structure and binding energy reveal that HbpRCBP6has a stronger affinity for OH-PCBs than for PCBs, indicating that the conversion of PCB by BphAB enzymes is a key step to improve the sensitivity of WCB. Subsequently, we developed an immobilized hydrogel WCB and a smartphone-based detection procedure to facilitate real-time and user-friendly PCB detection. This study will not only advance the biomonitoring of PCB contaminants but also provide an innovative strategy for developing metabolic pathway-sensing proteins combined biosensor.

Graphical Abstract
Pancreatic islets undergo functional and morphological adaptation during development of Barth Syndrome
Authors: Carlein Christopher , Hoffmann Markus D. A. , Amaral Andressa G. , Bickelmann Caroline , Lotfinia Ahmadali , de Selliers Laurie-Anne , Audoze-Chaud Johanne , Wrublewsky Selina , Lauterbach Marcel A. , von der Malsburg Karina , van der Laan Martin , Bozem Monika , Hoth Markus , Gilon Patrick , Ravier Magalie A. , Morgan Bruce , Ampofo Emmanuel , Maack Christoph , Roma Leticia Prates
Published: July 2024

Barth syndrome is a multisystem genetic disorder caused by mutation inTAFAZZIN, a gene that encodes a phospholipid:lysophospholipid transacylase important for cardiolipin remodeling. Barth Syndrome patients suffer from a number of symptoms including early heart failure, fatigue, and systemic metabolic alterations, including hypoglycemia. The endocrine pancreas is central to glucose homeostasis, however, the impact of defective cardiolipin remodeling on pancreatic islet function and the consequences for systemic metabolism is unclear. Surprisingly, in a mouse model with globalTAFAZZINknockdown, we observed improved glucose tolerance compared to wildtype littermates. We show that pancreatic islet metabolism and secretory function are robustly maintained through various compensatory mechanisms including increased glucose uptake and increased mitochondrial volume. Transcriptomics analyses revealed increased expression of genes encoding proteins involved in N-acetylglucosamine synthesis and proteinO-linked N-acetylglucosaminylation. These pathways might provide a molecular mechanism for coupling metabolic changes to mitochondrial volume regulation.
The inflammasome adaptor pycard is essential for immunity against Mycobacterium marinum infection in adult zebrafish
Authors: Uusi-Mäkelä Meri , Harjula Sanna-Kaisa E , Junno Maiju , Sillanpää Alina , Nätkin Reetta , Niskanen Mirja T , Nykter Matti , Rämet Mika
Published: July 2024

Inflammasome regulates the host response to intracellular pathogens including mycobacteria. We have previously shown that the course of Mycobacterium marinum infection in adult zebrafish (Danio rerio) has similar features than the course of tuberculosis in human. In this study, we have investigated the role of the inflammasome adaptor pycard in M. marinum infection in zebrafish. We produced two zebrafish knock-out mutant lines for the pycard gene with CRISPR/Cas9 mutagenesis. While the zebrafish larvae devoid of pycard develop normally and have unaltered resistance against M. marinum, the loss of pycard led to impaired survival and increased bacterial burden in the adult zebrafish. Based on histological analysis, immune cell aggregates, granulomas, were larger in pycard deficient fish compared to wild type controls. Transcriptome analysis with RNA sequencing of a zebrafish haematopoietic tissue, kidney, suggests a role for pycard in neutrophil mediated defence as well as in haematopoiesis and myelopoiesis during infection. Transcriptome analysis of fluorescently labelled kidney neutrophils further supported the importance of pycard for neutrophil-mediated immunity against M. marinum. Genes associated with neutrophil degranulation, haematopoiesis and PI3K signalling were differentially expressed in the pycard deficient neutrophils when compared to wild type controls. All in all, our results indicate that pycard is essential for resistance against mycobacteria in adult zebrafish. Based on transcriptional profiling of pycard mutants, we postulate that pycard mutant phenotype is mediated in part via defects in neutrophil function including neutrophil degranulation.
Critical roles of ERK and Akt signaling in metabolically dependent memory formation inDrosophilalarvae
Authors: Franz Hanna R. , Widmann Annekathrin
Published: July 2024

In the fruit flyDrosophila, memory formation is intricately linked to metabolic state. Our previous findings showed that the preferential support of memory under increased energy levels is mediated by the insulin receptor in the mushroom body (MB), a key memory center in the insect brain. This study analyzed the role of the insulin receptor’s downstream pathways, Ras-Raf-MEK-ERK and PI3K/Akt, in metabolically dependent memory formation. We evaluated their impact on memory processes by employing RNA interference-mediated downregulation of key components, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), in the MB ofDrosophilalarvae. To enhance energy levels, larvae were fed sugar for 60 minutes prior to aversive olfactory conditioning. Our findings revealed that genetically downregulating ERK and Akt in the MB significantly impaired metabolically dependent memory formation, without affecting naive sensory perception or olfactory learning. Immunohistochemical analysis confirmed the presence of active forms of ERK and Akt in the MB, underscoring their roles in modulating memory processes under elevated energy levels. The pivotal roles of these kinases suggest a broader implication of insulin signaling in memory formation under different metabolic conditions, and illuminate the connections between metabolic regulation and memory dynamics in the MB.
Convergent reductive evolution in bee-associated lactic acid bacteria
Authors: Pontes Ana , Harrison Marie-Claire , Rokas Antonis , Gonçalves Carla
Published: July 2024

Abstract

Distantly related organisms may evolve similar traits when exposed to similar environments or engaging in certain lifestyles.

Several members of the Lactobacillaceae (LAB) family are frequently isolated from the floral niche, mostly from bees and flowers. In some floral LAB species (henceforth referred to as bee- associated), distinctive genomic (e.g., genome reduction) and phenotypic (e.g., preference for fructose over glucose or fructophily) features were recently documented. These features are found across distantly related species, raising the hypothesis that specific genomic and phenotypic traits evolved convergently during adaptation to the floral environment.

To test this hypothesis, we examined representative genomes of 369 species of bee-associated and non-bee-associated LAB. Phylogenomic analysis unveiled seven independent ecological shifts towards the floral niche in LAB. In these bee-associated LAB, we observed pervasive, significant reductions of genome size, gene repertoire, and GC content.

Using machine leaning, we could distinguish bee-associated from non-bee-associated species with 94% accuracy, based on the absence of genes involved in metabolism, osmotic stress, or DNA repair. Moreover, we found that the most important genes for the machine learning classifier were seemingly lost, independently, in multiple bee-associated lineages. One of these genes,adhE, encodes a bifunctional aldehyde-alcohol dehydrogenase associated with the evolution of fructophily, a rare phenotypic trait that was recently identified in many floral LAB species. These results suggest that the independent evolution of distinctive phenotypes in bee- associated LAB has been largely driven by independent loss of the same set of genes.

Importance

Several lactic acid bacteria (LAB) species are intimately associated with bees and exhibit unique biochemical properties with potential for food applications and honeybee health. Using a machine-learning based approach, our study shows that adaptation of LAB to the bee environment was accompanied by a distinctive genomic trajectory deeply shaped by gene loss. Several of these gene losses occurred independently in distantly related species and are linked to some of their unique biotechnologically relevant traits, such as the preference of fructose over glucose (fructophily). This study underscores the potential of machine learning in identifying fingerprints of adaptation and detecting instances of convergent evolution. Furthermore, it sheds light onto the genomic and phenotypic particularities of bee-associated bacteria, thereby deepening the understanding of their positive impact on honeybee health.
NREM sleep brain networks modulate cognitive recovery from sleep deprivation
Authors: Lee Kangjoo , Wang Yimeng , Cross Nathan , Jegou Aude , Razavipour Fatemeh , Pomares Florence B. , Perrault Aurore A , Nguyen Alex , Aydin Umit , Uji Makoto , Abdallah Chifaou , Anticevic Alan , Frauscher Birgit , Benali Habib , Dang-vu Thien Thanh , Grova Christophe
Published: July 2024

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.
Axonal Tau sorting depends on the PRR2 domain and 0N4R-specific interactions hint at distinct roles of Tau isoforms in synaptic plasticity
Authors: Bell-Simons M. , Buchholz S. , Klimek J. , Zempel H.
Published: July 2024

Tau pathology is a major hallmark of Alzheimer’s disease (AD) and related diseases, called tauopathies. While Tau is normally enriched in axons, somatodendritic missorting of the microtubule-associated protein is a key event in early disease development. Tau missorting promotes synaptic loss and neuronal dysfunction but the mechanisms underlying both normal axonal sorting and pathological missorting remain unclear. Interestingly, the disease-associated Tau brain isoforms show different axodendritic distribution, but the distinct role of these isoforms in health and disease largely unknown. Here, we aimed to identify domains or motifs of Tau and cellular binding partners that are required for efficient axonal Tau sorting, and we studied the differences of the isoform-specific Tau interactome. By using humanMAPT-KO induced pluripotent stem cell (iPSC)-derived glutamatergic neurons, we analyzed the sorting behavior of more than 20 truncated or phosphorylation-mutant Tau constructs, and we used TurboID-based proximity labelling and proteomics to identify sorting- and isoform-specific Tau interactors. We found that efficient axonal Tau sorting was independent of the N-terminal tail, the C-terminal repeat domains, and the general microtubule affinity of Tau. In contrast, the presence of the proline-rich region 2 (PRR2) was necessary for successful sorting. Our interactome data revealed peroxisomal accumulation of the Tau N-terminal half, while axonal Tau interacted with the PP2A activator HSP110. When we compared the interactome of 0N3R- and 0N4R-Tau, we observed specific interactions of 0N4R-Tau with regulators of presynaptic exocytosis and postsynaptic plasticity, which are partially associated with AD pathogenesis, such as members of the CDC42 pathway and the RAB11 proteins, while 0N3R-Tau bound to MAP4 and other cytoskeletal elements. In sum, our study postulates that axonal Tau sorting relies on the PRR2 domain but not on microtubule affinity, and unravels a potential isoform-specific role in synaptic function and AD-related dysfunction.
Anti-diabetic and anti-adipogenic effects of polyherbal formulationVaranadi kashayamwith a focus on incretin modulation
Authors: Thottappillil Anjana , Kouser Sania , Badiger Abhi V. , Pinto Priyanka Gladys , Ramachandran Srimathy , Janadri Suresh , Mudagal Manjunatha P , Kukkupuni Subrahmanya Kumar , Mohan S Suma , Vishnuprasad Chethala N.
Published: July 2024

Managing complex disease like diabetes requires a systems and network medicine approach. Polyherbal formulations used in Indian Systems of Medicines (ISMs) likeAyurvedaand their multi-targeted mode of action could be an effective way to bring out this systems biology pharmacology effect required for chronic diseases. These multi-component formulations are also served as sources for identifying novel ligands that interact with drug targets having systemic effects. The present study usesVaranadi Kashayam(VK), a polyherbal preparation used inAyurvedaclinical management of diabetes and its comorbidities, to demonstrate the systemic pharmacological action exerted by a formulation with a special focus on incretin modulation.In-vitroassays demonstrated the inhibitory potential of VA on α-glucosidase and DPP4 enzymes and adipogenesis. It also showed an increase in GLP-1 secretion from GLUTag cells. These observations were corroborated in thein-vivohigh-fat fed model of SD rats where VA increased GLP-1 secretion, improved the oral glucose tolerance and reduced body weight. Bioinformatics and computational biology analysis further identified Chebulinic acid, Terchebin and Chebulagic acid as the three major molecules showing stable docking and interactions with DPP4 when compared to the standard drug Vildagliptin. Network pharmacology analysis of VA revealed the potential involvement of AGE-RAGE signalling, Insulin resistance, Insulin signalling and lipid and atherosclerosis pathway along with other important signalling like FOXO signalling, cAMP and PI3K-AKT signalling in exerting the anti-diabetic and anti-obesity action. The present work provided a biological insight into the multi-targeted mode of action of a poly-herbal formulation the possible pharmacological networking through which the formulation modulates diverse disease related targets.
Drought tolerance as an evolutionary precursor to frost and winter tolerance in grasses
Authors: Schat Laura , Schubert Marian , Fjellheim Siri , Humphreys Aelys M.
Published: July 2024

Accumulating evidence is suggesting more frequent tropical-to-temperate transitions than previously thought. This raises the possibility that biome transitions could be facilitated by precursor traits. A wealth of ecological, genetic and physiological evidence suggests overlap between drought and frost stress responses, but the origin of this overlap, i.e. the evolution of these responses relative to each other, is poorly known. Here, we test whether adaptation to frost and/or severe winters in grasses (Poaceae) was facilitated by ancestral adaptation to drought. We used occurrence patterns across Köppen-Geiger climate zones to classify species as drought, frost and/or winter tolerant, followed by comparative analyses. Ancestral state reconstructions revealed different evolutionary trajectories in different clades, suggesting both drought-first and frost-first scenarios. A model of correlated evolution was not supported when transition rate heterogeneity was taken into account or compared to traits simulated under independent evolution. Our findings provide some support for ancestral drought tolerance facilitating transitions to cold, temperate biomes, at least in some clades. Different scenarios in different clades is consistent with present-day grasses being either cold or drought specialists, possibly as a consequence of trade-offs between different stress tolerance responses.