bluuebunny/crossref_metadata_2025_split huggingface dataset:
Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis
Authors: Rozenberg Serge , Vandromme Jean , Revercez Perrine , Valcarenghi Mathilde , Joris Aurélie 
Published: May 2022

Abstract
This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.
Effective Image Communication of Hormone Replacement Therapy Risks and Benefits
Authors: Rifkin Erik 
Published: May 2022

Abstract
This article focuses on the value of a unique graphic/image designed to communicate health risks and benefits related to the administration of hormone replacement therapy. It will demonstrate why equations, technical terms, and confusing rhetoric need not be used for communication to patients and others. The use of a “familiar” theater graphic (given the name Benefit/Risk Characterization Theater) will allow physicians and patients to share decision-making by visualizing tradeoffs through the use of a clearer format: example Benefit/Risk Characterization Theaters: breast cancer risks associated with hormone replacement therapy, effectiveness of estrogen in treating menopausal symptoms, and thromboembolic risk of taking estrogen for postmenopausal women. The article describes a practical, simple methodology that can be used in many countries to facilitate doctor-patient communication.
Individual Benefits and Risks of Intravaginal Estrogen and Systemic Testosterone in the Management of Women in the Menopause, With a Discussion of Any Associated Risks for Cancer Development
Authors: Laing Abbie J. , Newson Louise , Simon James A. 
Published: May 2022

Abstract
Several formulations of intravaginal oestrogen are available for the treatment of genitourinary syndrome of menopause (GSM). These are safe and effective treatments for the symptoms of GSM. Licensed doses of intravaginal oestrogen do not elevate systemic estradiol levels above the normal postmenopausal range with long term use and there is no evidence of an increased risk of coronary heart disease, stroke, thromboembolism, colorectal cancer, endometrial cancer, breast cancer or breast cancer recurrence with their use. This should reassure both women and their healthcare professionals and should lead to more women receiving these localised, vaginally administered hormonal treatments. Available evidence also suggests a positive safety profile for transdermal testosterone treatment when delivered at physiological concentrations.
Percutaneous auricular nerve stimulation (neuromodulation) for the treatment of pain: A proof-of-concept case report using total joint arthroplasty as a surrogate for battlefield trauma
Authors: Ilfeld Brian M. , Finneran John J. , Said Engy T. , Cidambi Krishna R. , Ball Scott T. 
Published: May 2022

BACKGROUND
There are few effective pain treatments following trauma on the battlefield other than opioids, which are limited by respiratory depression. Ultrasound-guided percutaneous peripheral nerve stimulation (“neuromodulation”) has been proposed as an analgesic, but requires physician-level skills, advanced equipment, and an hour to administer. In contrast, percutaneous auricular neuromodulation may be placed by a medic in the field under nonsterile conditions in a few minutes, theoretically provides analgesia for any anatomic location, has no side effects, and no significant risks. It therefore offers the potential to be applied quickly on the battlefield without any of the limitations of opioids. We propose total joint replacement as a surrogate for battlefield trauma and here present a case report to demonstrate proof of concept.

METHODS
Following open total knee or hip arthroplasty under spinal anesthesia, two patients had an auricular neuromodulation device applied within the recovery room. Patients were discharged with the unit and contacted daily for 7 days.

RESULTS
The devices were each applied in under 3 minutes without difficulty, were well tolerated during use, and removed without complication at home on Day 5. During use, neither patient experienced pain while lying, sitting, or ambulating. Neither required analgesics other than scheduled celecoxib; and a single tablet (50 mg) of tramadol for one patient on postoperative Days 3 and 4 for pain while lowering herself to a seated position. On Days 6 and 7, both patients experienced an increase in pain, one of whom required around-the-clock tramadol.

CONCLUSION
Ambulatory postoperative percutaneous auricular neuromodulation is feasible. In these two cases, it appears to have markedly reduced pain scores and opioid requirements free of systemic side effects during the week following major orthopedic surgery. Considering the potential of this modality to treat trauma on the battlefield without systemic side effects, additional investigation appears warranted.

LEVEL OF EVIDENCE
Therapeutic/care management; Level V.
Effect of exercise from a very early stage after intracerebral hemorrhage on microglial and macrophage reactivity states in rats
Authors: Tamakoshi Keigo , Maeda Madoka , Murohashi Nae , Saito Ami 
Published: May 2022

Objective
This study investigated the effects of exercise, starting very early after intracerebral hemorrhage (ICH), on microglia and macrophages in a rat model. Collagenase solution was injected into the left striatum to induce ICH.

Methods
Rats were randomly assigned to receive placebo surgery without exercise (sham surgery), ICH without exercise (ICH), or ICH with very early exercise (ICH + VET). The ICH + VET group was subjected to treadmill running 6 h, 24 h, and days 2–6 after ICH. Motor function assessment was performed using the ladder test and rotarod test 3 h, 25 h, and 7 days after ICH. Postexercise brain tissue was collected on day 8 after surgery to investigate the lesion volume. Very early exercise temporarily worsened motor dysfunction. The protein expression levels of the macrophage and microglial markers CD80, CD163, and TMEM119 were analyzed 6 h, 24 h, and 8 days after ICH. Protein analysis of NeuN, GFAP, and PSD95 was also performed on day 8 after ICH.

Results
There was no significant difference in lesion volume between the ICH and ICH + VET groups on day 8 after ICH. Exercise from very early stage prevented elevated CD163 protein expression.

Conclusion
Very early exercise may inhibit the activation of anti-inflammatory-associated macrophages/microglia.
eEF1A2 knockdown impairs neuronal proliferation and inhibits neurite outgrowth of differentiating neurons
Authors: Rumpansuwon Kanitin , Prommahom Athinan , Dharmasaroja Permphan 
Published: May 2022

Objectives
The translation elongation factor-1, alpha-2 (eEF1A2) plays an important role in protein synthesis. Mutations in this gene have been described in individuals with neurodevelopmental disorders. Here, we silenced the expression of eEFA2 in human SH-SY5Y neuroblastoma cells and observed its roles in neuronal proliferation and differentiation upon induction with retinoic acid.

Methods
eEF1A2 were silenced using siRNA transfection. Cell proliferation was qualitatively evaluated by Ki-67 immunocytochemistry. Neuronal differentiation was induced with retinoic acid for 3, 5, 7 and 10 days. Neurite length was measured. The expression of microtubule-associated protein 2 (MAP2) was analyzed by western blotting. Tyrosine hydroxylase expression was visualized by immunofluorescence. Cytotoxicity to a neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and western blotting of cleaved caspase-3.

Results
eEF1A2 knockdown suppressed the proliferative activity of undifferentiated SH-SY5Y cells as shown by decreased Ki-67 immunostaining. Upon retinoic acid-induction, differentiated neurons with eEF1A2 knockdown exhibited shorter neurite length than untransfected cells, which was associated with the reduction of tyrosine hydroxylase and suppression of MAP2 at 10 days of differentiation. eEF1A2 knockdown decreased the survival of neurons, which was clearly observed in undifferentiated and short-term differentiated cells. Upon treatment with MPP+, cells with eEF1A2 knockdown showed a further reduction in cell survival and an increase of cleaved caspase-3 protein.

Conclusions
Our results suggest that eEF1A2 may be required for neuronal proliferation and differentiation of SH-SY5Y cells. Increased cell death susceptibility against MPP+ in eEF1A2-knockdown neurons may imply the neuroprotective role of eEF1A2.
The presence of occlusion affects electroencephalogram activity patterns when the target is occluded and immediately before occlusion
Authors: Koshizawa Ryo , Oki Kazuma , Takayose Masaki 
Published: May 2022

Objective
The objective of this study was to clarify the differences in electroencephalogram (EEG) activity patterns during the eye movements required to trace visible and occluded moving targets with millisecond temporal resolution.

Methods
To achieve this objective, we simultaneously measured EEG and eye-tracking during a task that required tracking moving targets that were partially occluded. These EEG and eye tracker parameters were compared with those of a nonoccluded task, a control task in which the moving target was fully visible.

Results
Differences in EEG activity patterns in the parietal eye field and posterior parietal lobe were observed during the occluded sections in the occluded task compared with the nonoccluded task. Under the same conditions, differences in EEG activity patterns in the middle temporal visual area, posterior parietal lobe, premotor, primary motor cortex, and temporal lobe were observed during visible sections in the occluded task compared with the nonoccluded task.

Conclusion
These results indicate that the presence of occlusion affects EEG activity patterns not only when the target is occluded but also immediately before occlusion.
Volumetric changes in specific neurofunctional subfields of the hippocampus in major depressive disorder
Authors: Wang Yuning , Wang Yi , Zhou Jing , Ge Chenjin , Shi Yin , Hu Zhihai 
Published: May 2022

Objective
There is evidence that hippocampal volume is abnormal in patients with major depressive disorder (MDD), but there have been no studies on volumetric changes in different subfields based on functional topography. This was investigated in the present study by comparing hippocampal neurofunctional subfield volumes between MDD patients and healthy control (HC) subjects.

Methods
Patients with MDD (n = 44) and HCs (n = 27) recruited at Shanghai Traditional Chinese Medicine Integrated Hospital underwent a T1-weighted anatomical MRI scan in the sagittal orientation, and the data were used to calculate hippocampal subfield volumes. Logistic regression was used to evaluate the association between the volumes and risk of MDD. A nomogram for predicting MDD risk based on volume changes in different subfields was developed, and its predictive power was evaluated by calculating the concordance (C)-index.

Results
Compared with HCs, MDD patients showed reduced volume in hippocampal neurofunctional subfields, specifically in left (L)1, right (R)1, and R2 (related to emotion) and L2, L3, and R4 (related to cognition and perception). The logistic regression analysis revealed that the risk of MDD was 4.59-, 5.8-, 8.33-, and 6.92-fold higher with atrophies of L1, L2, L3, and R4, respectively. A nomogram for predicting MDD risk was developed based on age; sex; and hippocampal L1, L2, L3, and R4 subfield volumes and showed good accuracy, with a C-index of 0.784.

Conclusion
Volumetric changes in the neurofunctional subfield of the hippocampus are potential imaging markers that can predict the occurrence of MDD.
Alterations in white matter microstructural properties after lingual strength exercise in patients with dysphagia
Authors: Krekeler Brittany N , Hou Jiancheng , Nair Veena A. , Prabhakaran Vivek , Rusche Nicole , Rogus-Pulia Nicole , Robbins JoAnne 
Published: May 2022

Objectives
Central nervous system effects of lingual strengthening exercise to treat dysphagia remain largely unknown. This pilot study measured changes in microstructural white matter to capture alterations in neural signal processing following lingual strengthening exercise.

Methods
Diffusion-weighted images were acquired from seven participants with dysphagia of varying etiologies, before and after lingual strengthening exercise (20 reps, 3×/day, 3 days/week, 8 weeks), using a 10-min diffusion sequence (9 b0, 56 directions with b1000) on GE750 3T scanner. Tract-Based Spatial Statistics evaluated voxel-based group differences for fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity and local diffusion homogeneity (LDH). Paired t-tests evaluated treatment differences on each metric (P < 0.05).

Results
After lingual strengthening exercise, lingual pressure generation increased (avg increase = 46.1 hPa; nonsignificant P = 0.52) with these changes in imaging metrics: (1) decrease in fractional anisotropy, forceps minor; (2) increase in mean diffusivity, right inferior fronto-occipital fasciculus (IFOF); (3) decrease in mean diffusivity, left uncinate fasciculus; (4) decrease in axial diffusivity, both left IFOF and left uncinate fasciculus; (5) increase in LDH, right anterior thalamic radiation and (6) decrease in LDH, temporal portion of right superior longitudinal fasciculus. There was a positive correlation between diffusion tensor imaging metrics and change in lingual pressure generation in left IFOF and the temporal portion of right superior longitudinal fasciculus.

Conclusions
These findings suggest that lingual strengthening exercise can induce changes in white matter structural and functional properties in a small group of patients with dysphagia of heterogeneous etiologies. These procedures should be repeated with a larger group of patients to improve interpretation of overall lingual strengthening exercise effects on cortical structure and function.
Impact of hierarchical processing levels on division of labor: neural electrophysiological evidence from a joint rule shifting
Authors: Han Jiahui , Guan Lei , Zhu Chengdong 
Published: May 2022

Objectives
Although previous studies have revealed the behavioral and neural mechanisms underlying cognitive control, the neural electrophysiological process in joint task switching has rarely been discussed. Moreover, the hierarchy process remains unclear. Therefore, the present study aimed to explore the neural mechanism of a target when two actors use division of labor between action selections in a joint hierarchical rule-shifting situation.

Methods
The present study employed a joint hierarchical rule shifting paradigm, and each participant was responsible for the selection of one type of action (left key and right key). The cue was the letter ‘R’ with three features, which indicated the hierarchical rule of the current trial. The target was an Arabic numeral (1–9, except 5). Participants made a magnitude judgement or a parity judgment based on the high and low hierarchical features of cues.

Results
The P2 component was smaller in the high-shift condition than in the repeat condition; however, the high-shift condition elicited a larger N2 amplitude than the low-shift and repeat conditions. We believe that the current P2 is related to selective attention to the hierarchical features of rules, and N2 is related to conflict control. In addition, the high-shift condition had the largest P3 amplitude, which indicates that this condition has the largest extent of update and leads to the most unstable association between rule and stimuli.

Conclusions
The study demonstrated that participants had dynamic brain responses to target stimuli in the joint rule-shifting situation. In other words, participants first confirmed the actor of the current target and then processed the target stimuli themselves.
First direct observation of ‘elongated’ conformational states in α-synuclein upon liquid-liquid phase separation
Authors: Ubbiali Daniele , Fratini Marta , Piersimoni Lolita , Ihling Christian H. , Kipping Marc , Heilmann Ingo , Iacobucci Claudio , Sinz Andrea 
Published: May 2022

Abstractα-Synuclein (α-syn) is an intrinsically disordered protein (IDP) that undergoes liquid-liquid phase separation (LLPS), fibrillation, and forms insoluble intracellular Lewy’s bodies in neurons, which are the hallmark of Parkinson’s Disease (PD). Neurotoxicity precedes the formation of aggregates and is probably related to LLPS of α-syn in the cell. The molecular mechanisms underlying the early stages of LLPS are still elusive. To obtain structural insights into α-syn upon LLPS, we take advantage of cross-linking/mass spectrometry (XL-MS) and introduce an innovative approach, termed COMPASS (COMPetitive PAiring StatisticS). COMPASS unravels transient interactions between α-syn molecules in liquid droplets. In this work, we show that the conformational ensemble of α-syn shifts from a ‘hairpin-like’ structure towards more ‘elongated’ conformational states upon LLPS. We obtain insights into the critical initial stages of PD and establish a novel mass spectrometry-based approach that will aid to solve open questions in LLPS structural biology.
Evolutionarily conserved effects of Notch signaling drive intestinal graft-versus-host disease in mice and non-human primates
Authors: Tkachev Victor , Vanderbeck Ashley , Perkey Eric , Furlan Scott N. , McGuckin Connor , Atria Daniela Gómez , Gerdemann Ulrike , Rui Xianliang , Lane Jennifer , Hunt Daniel J. , Zheng Hengqi , Colonna Lucrezia , Hoffman Michelle , Yu Alison , Kelly Samantha , Allman Anneka , Burbach Brandon , Shimizu Yoji , Panoskaltsis-Mortari Angela , Chen Guoying , Carpenter Stephen M. , Harari Olivier , Kuhnert Frank , Thurston Gavin , Blazar Bruce R. , Kean Leslie S. , Maillard Ivan 
Published: May 2022

AbstractNotch signaling promotes T-cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like ligand DLL4. To assess if Notch’s effects are evolutionarily conserved and identify key mechanisms, we studied antibody-mediated DLL4 blockade in a non-human primate model similar to human allo-HCT. Short-term DLL4 blockade improved post-transplant survival with striking, durable protection from gastrointestinal GVHD, out of proportion to other disease sites. Unlike prior immunosuppressive strategies, anti-DLL4 interfered with a T-cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin a4b7 in conventional T-cells via b1 competition for a4 binding, while preserving a4b7 in regulatory T-cells. Thereby, DLL4/Notch blockade decreased effector T-cell infiltration into the gut, with increased regulatory to conventional T-cell ratios early after allo-HCT. Our results identify a conserved, biologically unique and targetable role of DLL4/Notch signaling in GVHD.One Sentence SummaryNotch signaling promotes pathogenic effector T cell infiltration of the intestine during acute graft-versus-host disease.
Mixture Margin Random-effects Copula Models for Inferring Temporally Conserved Microbial Co-variation Networks from Longitudinal Data
Authors: Deek Rebecca A. , Li Hongzhe 
Published: May 2022

AbstractLongitudinal microbiome studies, in which data on a single subject is collected repeatedly over time, are becoming increasingly common in biomedical research. Such studies provide an opportunity to study the inherently dynamic nature of a microbiome in a way that cannot be done using cross-sectional studies. In this paper, we develop random-effects copula models with mixed zero-beta margins to identify biologically meaningful temporally conserved co-variation between two bacterial taxa, while accounting for the excessive zeros seen in 16S rRNA and metagenomic sequencing data. The model assumes a random-effects model for the dependence parameter in the copulas, which captures the conserved microbial co-variation while allowing for a time-specific dependence parameters. We develop a Monte Carlo EM algorithm for efficient estimation of model parameters and a corresponding Monte Carlo likelihood ratio test for the mean dependence parameter. Simulation studies show that our test controls the Type I error rate and provides an unbiased estimate of the mean dependence parameter. Additionally, we apply our method to a longitudinal pediatric cohort and identify changes in both local and global patterns of microbial co-variation networks in infants treated with antibiotics. Our analysis shows that the no antibiotics network is less dependent on individual taxon, thus making it more stable than the antibiotics network and more robust to both targeted and random attacks.Author summaryIdentification of co-variation between two microbes in microbial communities provides important insights into the community structure and stability. The commonly used measures of co-variation do not handle excessive zeros observed in the data and cannot be applied to longitudinal microbiome data directly. In this paper, we develop random-effects copula models with mixed zero-beta margins to identify biologically meaningful temporally conserved co-variation between two bacterial taxa, while accounting for the excessive zeros seen in 16S rRNA and metagenomic sequencing data. The model captures the conserved microbial co-variations while allowing for a time-specific dependence parameters. We develop an efficient Monte Carlo-based algorithm for parameter estimation and statistical inference. We analyze the data from a pediatric longitudinal cohort and identify changes in both local and global patterns of microbial co-variation networks in infants treated with antibiotics.