bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidisciplinary management based on clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage: A randomized controlled trial
Authors: Zhang Lan , Shen Tingting , Zhou Yan , Xie Xing , Wang Jing , Gao Haixiao
Published: April 2024

Objective:

To explore the effectiveness of multidisciplinary management based on a clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage (HICH).

Methods:

A total of 124 patients with HICH admitted to our hospital between February 2021 and June 2023 were selected as research subjects in this randomized, controlled, unblinded study. They were divided into Control-group and Study-group using a random number table method, with 62 cases in each group. The Control-group received routine care and the Study-group adopted a multidisciplinary management approach based on the clinical nursing pathway model. A multidisciplinary intervention group including 1 attending physician, 1 psychotherapist, 1 nutritionist, 1 rehabilitation specialist, and 4 responsible nurses was constructed. From preoperative to postoperative day, patients were provided with psychological intervention, health education, respiratory tract management, and specific care for patients who were restless. One to 3 days after operation, the patients and their family members were guided in basic postoperative care and nutrition care. From the 4th day after surgery to the 1st day before discharge, patients were guided for rehabilitation exercises. Patients also received discharge advices upon discharge. Activities of daily living, neurological function, stress response indicators, incidence of complications, and nursing satisfaction before and after the intervention were compared between the 2 groups.

Results:

After the intervention, the activities of daily living and neurological function of the 2 groups were significantly improved compared to before the intervention, and the Study-group was significantly higher than the Control-group (P < .05). After intervention, the levels of stress response indicators in both groups significantly decreased compared to before the intervention, and the Study-group was significantly lower than the Control-group (P < .05). The incidence of complications in the Study-group (3.23%) was lower than that in the Control-group (15.00%) (P < .05). Nursing satisfaction in the Study-group (95.16%) was higher than that in the Control-group (83.33%) (P < .05).

Conclusions:

Our findings indicate that adopting a multidisciplinary management approach based on clinical nursing pathways to intervene in patients with HICH can reduce stress response levels, reduce the risk of complications, and facilitate the recovery of neurological function and activities of daily living with high patient satisfaction.
The Nocebo Effect: A Bias in Clinical Practice—An Ethical Approach
Authors: Răducan-Florea Iulia-Virginia , Leaşu Florin G. , Dinu Eleonora A. , Rogozea Liliana M.
Published: April 2024

Background:

The nocebo effect is often disregarded in medical practice and is certainly much less known than the placebo effect, although, in reality, both can influence therapeutic decision making and the quality of life of patients. However, the nocebo effect raises a number of issues not only of a practical nature related to clinical activity but also ethical dilemmas related to the observance of the patient's autonomy, nonmaleficence, or informed consent and the information on which it is based.

Areas of Uncertainty:

The ethical dilemmas raised by the nocebo effect revolve around how informed consent can be achieved, the accuracy and volume of information that is transmitted to the patient, and how to report negative side effects of therapeutic treatment.

Data Sources:

In September 2023, a narrative analysis of the literature was conducted using a combination of keywords such as nocebo, placebo, ethics, therapeutic relationship from PubMed, Scopus, Google Scholar, and so on, as well as from official documents developed at an international level (World Health Organization), for a period of 10 years (2012–2021).

Results:

Analyzing the articles that remarked upon the significant impact of ethics in nocebo research or in the therapeutic relationship, we can state that the existence of several relevant issues of interest have been detected regarding the ethical use of nocebo and its impact in research or in clinics and thus the need for proper knowledge and management of the impact of nocebo effects. The ethical paradox of obtaining informed consent with the 2 goals, first, the need for complete information and second, the preservation of the autonomy of the patient, respectively, that of “primum non-nocere” and of avoiding unnecessary harm by revealing probable adverse effects is a point of interest for numerous studies. The potential for a nocebo effect is present when we inform patients about the risks and benefits of treatment, there being a clear link between the moral and ethical duty to inform patients and the need to avoid situations that increase the nocebo impact on how the disease or the adverse effects of the treatment are perceived. Adapting information about the side effects of medicines should focus on ensuring a balance between transparency and caution, especially in patients with a high potential for nocebo effect.

Conclusions:

The nocebo effect had for a long time been unknown or denied, although it can interfere with the results of the treatment used. As the nocebo phenomenon becomes increasingly known in medical practice, the clinical and ethical implications are identified by medical staff, and nocebo's adverse responses are no longer ignored.
FDG PET in Neurological Manifestations of COVID-19
Authors: Seniaray Nikhil , Verma Ritu , Ranjan Rajeev , Belho Ethel
Published: April 2024

Both the central and peripheral nervous systems can be affected in COVID-19. Although MRI is the primary investigative tool for neurological imaging, FDG PET may show additional areas of involvement in the brain in the form of regional hypometabolism or hypermetabolism, secondary to synaptic dysfunction and electrical or glial activation. We present a case series of 4 patients who had neurological symptoms attributable to COVID-19 infection with abnormalities in the brain FDG PET scan.
Omental Hernia as a Potential Cause of False-Positive GI Bleeding on 99mTc-RBC Scintigraphy
Authors: Karamian Farivash , Sahafi Pegah , Saber Tanha Amin , Sadeghi Ramin
Published: April 2024

Gastrointestinal bleeding scintigraphy is a noninvasive study used to determine the presence of active bleeding, localize the bleeding site, and estimate the bleeding volume for prognostic purposes in patients with suspected gastrointestinal bleeding. However, it is important to note that false-positive results can occur due to various reasons. In this case, we present the scenario of a middle-aged woman who exhibited symptoms of gastrointestinal bleeding and underwent 99mTc-RBC scintigraphy. The imaging revealed an accumulation of radiotracer in the hypogastric region, which was later determined to be caused by an omental hernia on SPECT/CT images. The herniated structure caused congestion in the mesenteric vessels, leading to the accumulation of 99mTc-RBC. This case highlights the significance of considering anatomical anomalies and nonbleeding pathologies when interpreting the 99mTc-RBC scintigraphy results for gastrointestinal bleeding.
Development of Opioid Use Disorder After Breast Reconstruction
Authors: Groff Destin , Freedman Zachary , Gilles Ambroise , Bone Curtis , Johnson Timothy Shane
Published: April 2024

Introduction

After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD.

Methods

A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use.

Results

There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268–6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977–3.458; 36 months HCV: OR, 3.718; CI, 2.268–6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502–4.935).

Conclusions

Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted.
Fourteen-Year Experience in Burn Eyelid Reconstruction and Complications Recurrence
Authors: Jeong Tiffany , Alessandri-Bonetti Mario , Liu Hilary , Pandya Sumaarg , Stofman Guy M. , Egro Francesco M.
Published: April 2024

Background

Loss of vision and other ocular defects are a concern with eyelid burn sequelae. This most commonly progresses from eyelid contracture to cicatricial ectropion and lagophthalmos. When left untreated, these may lead to exposure keratitis, ulceration, infection, perforation, and loss of vision. In the case of full-thickness eyelid burns, release and grafting are required. However, there is a paucity of studies on outcomes in eyelid burn surgery treatment, despite concern for permanent ocular damage or loss of vision. The aim of the study is to describe the complication rates in burn eyelid reconstruction at a single center for 14 years.

Methods

A retrospective cohort study was performed of all patients who had sustained eyelid burns and required reconstruction between April 2009 and February 2023. Medical records were obtained from patients' charts. Collected data include demographics, medical history, type of injury, indication for surgery, procedure performed, and complications.

Results

A total of 14 patients and 25 eyelids underwent eyelid reconstruction of the 901 total patients with burn-related injuries requiring plastic surgery reconstruction. These patients underwent 54 eyelid surgeries with a mean follow-up time of 13.1 ± 17.1 months. Patients were 71% men and 29% women, with a mean age of 45.1 ± 15.6 years. In 53.7% (n = 29) of the cases, the simultaneous reconstruction of both the upper and lower eyelids was necessary. The reconstruction of the upper and lower eyelid alone represented a smaller percentage (25.9% and 20.4%, respectively). On average, the patients received 3.9 ± 3.5 eyelid surgeries. The overall complication rate was 53.7% (n = 29). The most common complication was ectropion (42.6%, n = 23). Other complications included eye injury (25.9%, n = 14), lagophthalmos (24.1%, n = 13), local infection (7.4%, n = 4), and graft loss (5.6%, n = 3).

Conclusion

Periorbital burns represent a major challenge that may require complex surgical intervention. Full-thickness skin graft remains the standard of care for patients with eyelid burns. However, there is a high incidence of ectropion that may require reoperation. Further studies examining the conditions of successful eyelid burn procedures may provide guidance on when patients may benefit from eyelid reconstruction during their burn treatment.
Socioeconomic Disparities in Postoperative Outcomes of Osteocutaneous Fibula Free Flaps for Head and Neck Reconstruction
Authors: Njoroge Moreen W. , Karwoski Allison S. , Gornitsky Jordan , Resnick Eric , Galaria Alina , Lopez Christopher D. , Boahene Kofi D. O. , Yang Robin
Published: April 2024

Background

Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer.

Methods

A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications.

Results

The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000–$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205–0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050–0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000–$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035–0.940; P = 0.042). No significant difference was found in the >$150,000 group.

Conclusions

Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI.
Assessing Long-Term Volume Retention in Breast Fat Grafting
Authors: Chen Yunchan , Arbuiso Sophia , Vernice Nicholas A. , Black Grant G. , Wang Marcos Lu , Liao Matthew W. , Medina Samuel J. , Brown Kristy A. , Otterburn David
Published: April 2024

Introduction

Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery.

Methods

A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change.

Results

The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05).

Discussion

Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis.
Intensive Blood Pressure Lowering Improves Left Ventricular Geometry in Older Hypertensive Patients: The STEP Trial
Authors: Deng Yue , Zhang Juyan , Chen Zhenzhen , Bai Jingjing , Yang Xiaomin , Yu Chunli , Yu Jing , Cai Jun
Published: April 2024

Background

The effect of intensive systolic blood pressure (SBP) lowering on left ventricular (LV) geometry remains unclear.

Methods

Patients with hypertension aged 60–80 years without prior stroke were enrolled from 42 centers across China from January 2017. Eligible patients were randomly assigned to intensive (target: 110 to <130 mmHg) or standard (target: 130 to < 150 mmHg) SBP-lowering treatment. LV mass (LVM) was assessed by two-dimensional, M-mode, color flow Doppler echocardiography. LV hypertrophy (LVH) was diagnosed according to LVM index (LVMI) to height1.7using sex-specific thresholds.

Results

Baseline demographic and LV parameters were comparable between the groups (n = 5709). During the median follow-up of 2.63 years, intensive treatment was associated with a lower risk of new LVH (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.69–1.00,P= 0.051) and greater regression of mean LVMI by 0.38 g/m1.7per year (95% CI 0.05–0.71,P= 0.024). The rate of baseline LVH regression did not differ between the groups. Male patients achieved a significantly greater benefit from intensive treatment than female patients in terms of new LVH prevention and baseline LVH regression (bothPfor interaction <0.10). The favorable effect of intensive treatment on the cardiovascular outcome (HR 0.73, 95% CI 0.54–1.00) was slightly attenuated after adjusting for LVMI as a time-varying covariate (HR 0.75, 95% CI 0.55–1.03).

Conclusions

In older patients with hypertension, intensive SBP lowering offers additional cardiovascular benefits in terms of LV geometry. This favorable effect partially explains the reduction in cardiovascular events.

Trial registration

Clinicaltrials.gov(Identifier:NCT03015311)

Condensed Abstract

This is the first randomized controlled trial with a sufficient sample size to compare the effect of intensive systolic blood pressure (SBP) lowering (<130 mmHg) on echocardiographic left ventricular (LV) geometry with that of standard SBP lowering (< 150 mmHg) in older patients with hypertension. A lower risk of new LV hypertrophy development and greater regression of LV mass index were observed in patients with intensive treatment than in those with standard treatment. This favorable effect partially explains the reduction in cardiovascular events associated with intensive SBP lowering.
Effect of urbanisation on soil and plant pollution in province of Valencia, Spain
Authors: Edina Simon , Bin Ismail Haziq , Sipos Bianka , Abriha-Molnar Vanda Eva , Abriha David , Andreu-Sanchez Oscar , Boluda Rafael , Perez Luiz Roca
Published: March 2024

The accumulation of the toxic metals can result in the degradation of neighboring ecosystems and reducing their value to humans in terms of aesthetic properties and utility. Therefore, the aim of our research was to investigate the effect of urbanization on metal levels in soil samples and Citrus sp. tree leaves along an urbanization (rural, periurban and urban) in Valencia (Spain). There were significant differences for the content of clay, pH, electrical conductivity (EC), soil organic matter (SOM), concentration of Ca and exchangeable sodium percentage (ESP). A significant difference was not found in the case of elemental concentration of soil. There were significant differences for the concentration of Cu on Citrus sp. leaves, only. Based on our findings Valencia did not exhibit a significant relationship between the element concentrations and the urban gradient except for the case of copper in the leaf samples. The find no difference in the soil indicate the homogenous nature of the Valencia soil.
Transcranial direct current stimulation modulates primate brain dynamics across states of consciousness.
Authors: Hoffner Guylaine , Castro Pablo , Uhrig Lynn , Signorelli Camilo Miguel , Dupont Morgan , Tasserie Jordy , Destexhe Alain , Cofre Rodrigo , Sitt Jacobo , Jarraya Bechir
Published: March 2024

The resting primate brain is traversed by spontaneous functional connectivity patterns that show striking differences between conscious and unconscious states. Transcranial direct current stimulation, a non-invasive neuromodulatory technique, can improve signs of consciousness in disorders of consciousness, but can it influence conscious and unconscious dynamic functional connectivity? We investigated the modulatory effect of prefrontal cortex (PFC) transcranial direct current stimulation (tDCS) on brain dynamics in awake and anesthetized non-human primates using functional MRI. In awake macaques receiving either anodal or cathodal high-density tDCS (HD-tDCS), we found that cathodal stimulation robustly disrupted the repertoire of functional connectivity patterns, increased structure-function correlation, decreased Shannon entropy, and favored transitions towards anatomically-based patterns. Under deep sedation, anodal HD-tDCS significantly altered brain pattern distribution and reduced structure-function correlation. The prefrontal stimulation also modified dynamic connectivity arrangements typically associated with consciousness and unconsciousness. Our findings offer compelling evidence that PFC tDCS induces striking modifications in the fMRI-based dynamic organization of the brain across different states of consciousness. This study contributes to an enhanced understanding of tDCS neuromodulation mechanisms and has important clinical implications for disorders of consciousness.
Dynamic Gamma Modulation of Hippocampal Place Cells Predominates Development of Theta Sequences
Authors: Wang Ning , Wang Yimeng , Guo Mingkun , Wang Ling , Wang Xueling , Zhu Nan , Yang Jiajia , Wang Lei , Zheng Chenguang , Ming Dong
Published: March 2024

The experience-dependent spatial cognitive process requires sequential organization of hippocampal neural activities by theta rhythm, which develops to represent highly compressed information for rapid learning. However, how the theta sequences were developed in a finer time scale within theta cycles remains unclear. In this study, we found that sweep-ahead structure of theta sequences developing with exploration was predominantly dependent on a relatively large proportion of FG-cells, i.e. a subset of place cells dominantly phase-locked to fast gamma rhythms. These ensembles integrated compressed spatial information by cells consistently firing at precessing slow gamma phases within the theta cycle. Accordingly, the sweep-ahead structure of FG-cell sequences was positively correlated with the intensity of slow gamma phase precession, in particular during early development of theta sequences. These findings highlight the dynamic network-modulation by fast and slow gamma in the development of theta sequences which may further facilitate memory encoding and retrieval.
Sustained ON alpha retinal ganglion cells in the temporal retina exhibit task-specific regional adaptions in dendritic signal integration
Authors: Oesterle Jonathan , Ran Yanli , Stahr Paul , Kerr Jason ND , Schubert Timm , Berens Philipp , Euler Thomas
Published: March 2024

Various retinal ganglion cells (RGCs) show regional adaptations, for instance, to increase visual acuity. However, for many RGC types, it is not known how they vary in their signalprocessing properties across the retina. In the mouse retina, sustained ON alpha (sONα) RGCs were found to have differences in morphology and receptive field sizes along the nasotemporal axis, and temporal sONα RGCs are likely to play a role in visually guided hunting. Thus, we hypothesised that this cell type also exhibits regional adaptations on the level of dendritic signal processing and that these adaptations are advantageous for prey capture. Here, we measured dendritic signals from individual sONα RGCs at different locations in theexvivowhole-mount mouse retina using two-photon microscopy. We measured both postsynaptic Ca2+signals at the dendrites of individual RGCs and presynaptic glutamate signals from bipolar cells (BCs). We found that temporal sONα RGC dendrites exhibit, in addition to the expected sustained-ON signals with only weak surrounds, signals with strong surround suppression, which were not present in nasal sONα RGCs. This difference was also present in the excitatory presynaptic inputs from BCs, suggesting a presynaptic origin. Finally, using population models in an encoder-decoder paradigm, we showed that these adaptations might be beneficial for detecting crickets in hunting behaviour.
Elevated pyramidal cell firing orchestrates arteriolar vasoconstriction through COX-2-derived prostaglandin E2 signaling
Authors: Le Gac Benjamin , Tournissac Marine , Belzic Esther , Picaud Sandrine , Dusart Isabelle , Soula Hédi , Li Dongdong , Charpak Serge , Cauli Bruno
Published: March 2024

Neurovascular coupling, linking neuronal activity to cerebral blood flow, is essential for brain function and underpins functional brain imaging. Whereas mechanisms involved in vasodilation are well-documented, those controlling vasoconstriction remain overlooked. This study unravels the mechanisms by which pyramidal cells elicit arteriole vasoconstriction. Using patch-clamp recording, vascular and Ca2+imaging in mouse cortical slices, we show that strong optogenetic activation of layer II/III pyramidal cells induces vasoconstriction, correlating with firing frequency and somatic Ca2+increase.Ex vivoandin vivopharmacological investigations indicate that this vasoconstriction predominantly recruits prostaglandin E2 through the cyclooxygenase-2 pathway, and activation of EP1 and EP3 receptors. We also present evidence that specific interneurons releasing neuropeptide Y, and astrocytes, through 20-hydroxyeicosatetraenoic acid, contribute to this process. By revealing the mechanisms by which pyramidal cells lead to vasoconstriction, our findings shed light on the complex regulation of neurovascular coupling.

Significance statement

Cerebral blood flow is tightly controlled by neuronal activity, a process termed neurovascular coupling which serves as the physiological basis for functional brain imaging widely used to map neuronal activity in health and diseases. While the prevailing view links increased neuronal activity with enhanced blood perfusion, our data suggest that elevated neuronal activity can also reduce cerebral blood flow. By optically controlling the activity of pyramidal cells, we demonstrate that these excitatory neurons induce vasoconstriction when their action potential firing is increased by releasing glutamate and lipid messengers. These findings update the interpretation of functional brain imaging signals and help to better understand the etiopathogenesis of epilepsy and Alzheimer’s disease, in which hyperactivity, hypoperfusion and cognitive deficits overlap.
A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth and interactive QC with afni_proc.py and more
Authors: Taylor Paul A , Glen Daniel , Chen Gang , Cox Robert W , Hanayik Taylor , Rorden Chris , Nielson Dylan M , Rajendra Justin K , Reynolds Richard C
Published: March 2024

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically under-discussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include: a modular HTML document that covers full single subject processing from the raw data through statistical modeling; several review scripts in the results directory of processed data; and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block", as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.
Global DNA Hypomethylation as a Biomarker of Accelerated Epigenetic Ageing in Primates
Authors: Girling Michael T.S. , Sanchez Nofre M , Paredes Ursula M.
Published: March 2024

Introduction

Epigenetic clocks based on DNA methylation patterns provide a powerful tool for measuring biological ageing, but requiring genome-wide methylation data and high costs limits their broad application across species and populations.

Methods

We investigated whether simply quantifying global DNA methylation levels could serve as an inexpensive proxy for epigenetic ageing, using a captive colony of owl monkeys (Aotus nancymaae) using a colorimetric ELISA assay to measure proportional content of levels of blood and brain 5-methylcytosine (5-mC) across the genome, comparing owl monkeys with known exposures to ageing accelerators and controls.

Results

we found that global 5-mC declined significantly with chronological age in blood, and in the brain of parents. Notably, this age-related blood hypomethylation in individuals experiencing early life maternal rejection was accelerated. Parenting experience also accelerated DNA methylation loss with age, but this effect was specific to the brain and not seen in blood. Infection history did not impact blood 5-mC trajectories. Although multiple regression models did not replicate all findings, likely due to sample size constraints, our results demonstrate that global DNA hypomethylation tracks biological ageing in blood.

Discussion

This simple metric successfully detected accelerated epigenetic ageing induced by early adversity, as well as distinct patterns relating to reproductive investment in the brain - phenotypes typically identified by sophisticated epigenetic clocks. Quantifying global methylation thus provides a cost-effective alternative approach to assessing susceptibility to environmentally-driven accelerated ageing across primate species and populations where DNA methylation arrays or sequencing are impractical.
Multiple and subject-specific roles of uncertainty in reward-guided decision-making
Authors: Paunov Alexander , L’Hôtellier Maëva , Guo Dalin , He Zoe , Yu Angela , Meyniel Florent
Published: March 2024

Decision-making in noisy, changing, and partially observable environments entails a basic tradeoff between immediate reward and longer-term information gain, known as the exploration-exploitation dilemma. Computationally, an effective way to balance this tradeoff is by leveraging uncertainty to guide exploration. Yet, in humans, empirical findings are mixed, from suggesting uncertainty-seeking to indifference and avoidance. In a novel bandit task that better captures uncertainty-driven behavior, we find multiple roles for uncertainty in human choices. First, stable and psychologically meaningful individual differences in uncertainty preferences actually range from seeking to avoidance, which can manifest as null group-level effects. Second, uncertainty modulates the use of basic decision heuristics that imperfectly exploit immediate rewards: a repetition bias and win-stay-lose-shift heuristic. These heuristics interact with uncertainty, favoring heuristic choices under higher uncertainty. These results, highlighting the rich and varied structure of reward-based choice, are a step to understanding its functional basis and dysfunction in psychopathology.
Hippocampal Signal Complexity and Rate-of-Change Predict Navigational Performance: Evidence from a Two-Week VR Training Program
Authors: Ozubko Jason D. , Campbell Madelyn , Verhayden Abigail , Demetri Brooke , Brady Molly , Sivashankar Yadurshana , Brunec Iva
Published: March 2024

The hippocampus is believed to be an important region for spatial navigation, helping to represent the environment and plan routes. Evidence from rodents has suggested that the hippocampus processes information in a graded manner along its long-axis, with anterior regions encoding coarse information and posterior regions encoding fine-grained information. Brunec et al. (2018) demonstrated similar patterns in humans in a navigation paradigm, showing that the anterior-posterior gradient in representational granularity and the rate of signal change exist in the human hippocampus. However, the stability of these signals and their relationship to navigational performance remain unclear. In this study, we conducted a two-week training program where participants learned to navigate through a novel city environment. We investigated inter-voxel similarity (IVS) and temporal auto-correlation hippocampal signals, measures of representational granularity and signal change, respectively. Specifically, we investigated how these signals were influenced by navigational ability (i.e., stronger vs. weaker spatial learners), training session, and navigational dynamics. Our results revealed that stronger learners exhibited a clear anterior-posterior distinction in IVS in the right hippocampus, while weaker learners showed less pronounced distinctions. Additionally, lower general IVS levels in the hippocampus were linked to better early learning. Successful navigation was characterized by faster signal change, particularly in the anterior hippocampus, whereas failed navigation lacked the anterior-posterior distinction in signal change. These findings suggest that signal complexity and signal change in the hippocampus are important factors for successful navigation, with IVS representing information organization and auto-correlation reflecting moment-to-moment updating. These findings support the idea that efficient organization of scales of representation in an environment may be necessary for efficient navigation itself. Understanding the dynamics of these neural signals provides insights into the mechanisms underlying navigational learning in humans.
Characterisation of cuticle mechanical properties: analysing stiffness in layered living systems to understand surface buckling patterns
Authors: Airoldi Chiara A. , Chen Chao , Herrera-Ubaldo Humberto , Fu Hongbo , Lugo Carlos A. , Crosby Alfred J. , Glover Beverley J.
Published: March 2024

Development of a living organism is a highly regulated process during which biological materials undergo constant change.De novomaterial synthesis and changes in mechanical properties of materials are key for organ development; however, few studies have attempted to produce quantitative measurements of the mechanical properties of biological materials during growth. Such quantitative analysis is particularly challenging where the material is layered, as is the case for the plant cuticle on top of the plant epidermal cell wall. Here, we focus onHibiscus trionumflower petals, where buckling of the cuticle forms ridges, producing an iridescent effect. This ridge formation is hypothesised to be due to mechanical instability, which directly depends upon the mechanical properties of the individual layers within the epidermal cells. We present measurements of the mechanical properties of the surface layers of petal epidermal cells through atomic force microscopy (AFM) and the uniaxial tensile tester for ultrathin films (TUTTUT), across growth stages. We found that the wavelength of the surface ridges was set at the ridge formation stage, and this wavelength was preserved during further petal development, most likely because of the plasticity of the material. Our findings suggest that temporal changes in biological material properties are key to understanding the development of biological surface patterns.
Nonuniform scaling of synaptic inhibition in the dorsolateral geniculate nucleus in a mouse model of glaucoma
Authors: Van Hook Matthew J. , McCool Shaylah
Published: March 2024

Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6-7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feed-forward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the GABAA-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling indicated this was the result of an approximately 1.4-fold increase in GABA receptor number at post-synaptic inhibitory synapses, although several pieces of evidence strongly indicate a non-uniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP.

Significance Statement:

Elevated eye pressure in glaucoma leads to loss of retinal outputs to the dorsolateral geniculate nucleus (dLGN), which is critical for relaying information to the cortex for conscious vision. Alterations in neuronal activity, as could arise from excitatory synapse loss, can trigger homeostatic adaptations to synaptic function that attempt to maintain activity within a meaningful dynamic range, although whether this occurs uniformly at all synapses within a given neuron or is a non-uniform process is debated. Here, using a mouse model of glaucoma, we show that dLGN inhibitory synapses undergo non-uniform upregulation due to addition of post-synaptic GABA receptors. This is likely to be a neuronal adaptation to glaucomatous pathology in an important sub-cortical visual center.
Oncogenic Phase Transitions: How Mutant p53 Drives Amyloid Formation in p63 and p73 Liquid Droplets
Authors: Petronilho Elaine C. , de Andrade Guilherme C. , de Sousa Gileno dos S. , Almeida Fernando P. , Mota Michelle F. , Marques Mayra A. , Vieira Tuane C. R. G. , de Oliveira Guilherme A. P. , Silva Jerson L.
Published: March 2024

Phase separation (PS) of p53 is critical in its path to amyloid aggregation, a process linked to cancer. P63 and p73 exhibit dual roles as tumor suppressors and oncogenes and are often heightened in tumors. Their coaggregation has been proposed in cancer, yet their PS contribution remains unknown. This study investigates the phase behaviors of p53, p63, and p73. P63 and p73 undergo liquid-liquid phase separation (LLPS). Unlike p53, p63 and p73 do not form amyloids under increased temperatures, underscoring an aspect of the processes involved in cancer. Unlike p63 and p73, wild-type and the M237I mutant p53 initially form droplets at 4°C, but at temperatures up to 37°C, they begin to aggregate and bind to Congo red, showing amyloidogenesis. Intriguingly, mutant p53 promotes amyloid-like states in p63 and p73 and hijacks p73 into membrane less organelles. Wild-type p53 has a moderate effect on p63 and p73’s amyloid aggregation. Additionally, heparin prevents the prion-like aggregation of p63 and p73 induced by p53. Our results shed light on how mutant and wild-type p53 may trigger amyloid aggregation of p63 and p73, revealing the capacity of p53 amyloid droplets within cancer. These insights expand the possibilities for developing cancer therapies targeting the prion-like conversion of p63 and p73 influenced by mutated p53.

Relevance

The prion-like action of mutant p53 on p63 and p73 droplets would be the basis for an oncogenic gain of function of the p53 mutation.
MolSnapper: Conditioning Diffusion for Structure Based Drug Design
Authors: Ziv Yael , Marsden Brian , Deane Charlotte
Published: March 2024

Generative models have emerged as potentially powerful methods for molecular design, yet challenges persist in generating molecules that effectively bind to the intended target. The ability to control the design process and incorporate prior knowledge would be highly beneficial for better tailoring molecules to fit specific binding sites. In this paper, we introduce MolSnapper, a novel tool that is able to condition diffusion models for structure-based drug design by seamlessly integrating expert knowledge in the form of 3D pharmacophores. We demonstrate through comprehensive testing on both CrossDocked and Binding MOAD datasets, that our method generates molecules better tailored to fit a given binding site, achieving high structural and chemical similarity to the original molecules. It also, when compared to alternative methods, yields approximately twice as many valid molecules.
Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses
Authors: Dey Abhishek , Yan Shuting , Schlick Tamar , Laederach Alain
Published: March 2024

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.
HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation
Authors: Gendreizig Sarah , Martinez-Ruiz Laura , López-Rodríguez Alba , Pabla Harkiren , Hose Leonie , Brasch Frank , Busche Tobias , Escames Germaine , Sudhoff Holger , Scholtz Lars Uwe , Todt Ingo , Oppel Felix
Published: March 2024

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting treatment strategies are desperately needed. Using patient-derived tumor cells, we created an HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly, including TPM1, TAGLN, and ACTA1. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-likein vitrodifferentiation occurs in human tissue. A recent sarcoma study was able to turn rhabdomyosarcoma into muscle-like cells. We are the first to report that carcinoma cells can undergo a triggered myocyte differentiation. Our study suggests that the targeted myo-differentiation of tumor cells might be therapeutically valuable in HPV+ HNSCCs.
Research disturbance negatively impacts incubation behaviour of female Great tits
Authors: Clemencin Léanne , Barba Emilio , Diez-Méndez David
Published: March 2024

Human-induced disturbance is perceived by avian species as a predation risk. However, the anti-predatory behaviour triggered by these non-lethal events can have negative impacts on reproduction and offspring survival. Research on breeding birds often involves visits to their nests and is likely to disrupt parental behaviour, but nest visits that do not involve direct handling of females have been overlooked as important disturbance events. This study focuses on the impacts of short visits to the nest of incubating Great tit(Parus major) females. We investigated how long they stay away from the nest (off-bout) after a disturbance, their possible compensatory behaviour once they resume incubation (on-bout), and the effects on daily incubation rhythms. We used three years of data from two breeding populations to assess the consequences of disturbances in two scenarios: when the female is present in the nest and flushed, and when the female is absent. We found that after a disturbance, the immediate off-bout was longer when the female was either present or absent, with the magnitude of the disturbance being greater when females were flushed. Females did not compensate with longer on-bouts afterwards, i.e. the research disturbance altered daily incubation behaviour by reducing the total time spent on the nest in relation to the number of daily disturbance events. Females that alter their behaviour in response to perceived predation risk would perform longer incubation periods, resulting in lower hatching rates. These effects of research on female behaviour should be considered when planning field experiments.