bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Postoperative Hormonal Suppression on Fertility in Patients With Endometriosis After Conservative Surgery
Authors: Richard Evelyne , Morin Jessica , Murji Ally , Lemyre Madeleine , Laberge Philippe Y. , Maheux-Lacroix Sarah
Published: June 2022

OBJECTIVE:

To evaluate the effect of hormonal suppression on fertility when administered to infertile patients or patient wishing to conceive after surgery for endometriosis.

DATA SOURCES:

A systematic search of MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov was performed by two independent reviewers from the databases' inception until December 2020.

METHODS OF STUDY SELECTION:

We included randomized controlled trials comparing any suppressive hormonal therapy to an inactive control (placebo or absence of treatment) after conservative surgery for endometriosis. Studies that did not report fertility outcomes after surgery were excluded.

TABULATION, INTEGRATION AND RESULTS:

This systematic review and meta-analysis was registered in PROSPERO. Two reviewers extracted data and assessed the risk of bias as well as the strength of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. Relative risks (RRs) were pooled by quantitative random effect meta-analysis. From 3,138 citations, 19 trials (2,028 patients) were included. Overall, no difference was observed between the treatment and the control group for pregnancy (RR 1.15; 95% CI 1.00–1.32) and live births (RR 1.05; 95% CI 0.84–1.32). When pooling all hormonal therapies, the duration of administration of postoperative therapy was identified as a substantial source of heterogeneity between studies (I2 difference=74%) with increased chances of pregnancy compared with control when administered for at least 3 months (RR 1.22; 95% CI 1.04–1.43). Gonadotropin-releasing hormone (GnRH) agonists (14 trials, 1,721 patients) were associated with increased chances of pregnancy compared with placebo or no treatment (RR 1.20; 95% CI 1.03–1.41; I2=25%). Data were limited for other hormonal treatments with no significant difference between groups. Subgroup analyses taking into account the use of fertility treatments (insemination or in vitro fertilization), stages of the disease and risk of bias of included trials did not modify the results.

CONCLUSION:

Postoperative hormonal suppression should be considered on a case-by-case basis to enhance fertility while balancing this benefit with the risks of delaying conception. If chosen, GnRH agonists would be the treatment of choice, and a duration of at least 3 months should be favored.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42021224424.
Intermittent Soft-Tissue Tumor Enlargement in Episodic Angioedema With Eosinophilia Syndrome
Authors: Fernández Lucía T. , Ocampo-Candiani Jorge , Watts-Santos Anabella , Guerrero-Putz María D. , González-Díaz Sandra Nora , Zárate-Hernández María Del Carmen , Cantú-Rodríguez Olga G. , Herz-Ruelas Maira E.
Published: June 2022

Episodic hypereosinophilia and angioedema syndrome, also known as Gleich syndrome, is a rare entity characterized by recurrent episodes of eosinophilia, angioedema, urticaria, fever and weight gain with spontaneous resolution. It is classified as an idiopathic hypereosinophilic syndrome. Unlike other hypereosinophilic syndromes, it has a low risk for internal organ damage. We report the case of a 42-year-old male with a 28-year history of recurrent erythematous wheals and plaques and persistent hypereosinophilia. Physical examination revealed a well-defined subcutaneous nodule on his right lower limb that increased in size with each episode of angioedema. Histopathology evidenced a lipoma with intense eosinophil infiltration within the mature adipose tissue, while the specimen of the wheal revealed scarce perivascular and interstitial eosinophilic inflammatory infiltrate. Diagnosis of episodic angioedema with eosinophilia syndrome was made based on clinical and laboratory findings.
Is Developmental Regression in Down Syndrome Linked to Life Stressors?
Authors: Sargado Sabrina , Milliken Anna L. , Hojlo Margaret A. , Pawlowski Katherine G. , Deister Diana , Soccorso Cara N. , Baumer Nicole T.
Published: June 2022

Objective:

Unexplained regression in Down syndrome (URDS) involves a loss of acquired skills resulting in functional deterioration. Despite extensive workup and treatment, few individuals regain baseline function. This study aimed to understand the role of psychosocial stressors in URDS.

Methods:

We describe psychosocial stressors in 14 cases of URDS. Specifically, we examined psychosocial stressors in the context of presentation and clinical symptoms. We also examined co-occurring neurodevelopmental disorders and medical and mental health conditions.

Results:

All individuals experienced psychosocial stressors within one year of diagnosis of URDS. The most common psychosocial stressors were moving to a new home or school.

Conclusion:

Psychosocial stressors are commonly reported preceding URDS. Knowledge about psychosocial stressors' impact may lead to preventive interventions, improved monitoring, and earlier diagnosis. Future research should focus on understanding psychosocial stressors to help identify individuals at risk for URDS and contribute to treatment.
Entrapped temporal horn syndrome: a retrospective analysis of 5 case series
Authors: Zhuang Yan , Richard Seidu A. , Zhou Jiahao , Liu Jun , Fang Zhen , Chen Zejun
Published: June 2022

Introduction:

Entrapped temporal horn (ETH) syndrome is a rare form of localized noncommunicating hydrocephalus, which is often associated with the treatment of lesions around the trigone area (atrium) of the lateral ventricles. So far, only a few cases have been reported in the literature. Thus, we present our experience with the causes and management of patients with ETH syndrome at our institution.

Materials and method:

We retrospectively analyzed clinical data of 5 patients with ETH syndrome treated at our facility from July 2018 to August 2021. Patients’ data such as age, sex, initial disease, clinical presentation, radiologic diagnosis, treatment, and outcomes were documented and analyzed.

Results:

Our patients comprise of 3 females and 2 males. Their ages ranged from 42 to 85 years, with a mean age of 62 years. Postoperative adhesions caused ETH in 3 patients while meningioma and intracranial infection cause the ETH in 2 patients, respectively. One patient was treated via craniotomy, 3 patients were treated via shunting while 1 patient was treated conservatively. The ETH resolved in 4 patients, while no resolution was attained in 1 patient.

Conclusion:

Definitive treatments via craniotomy or shunting were capable of resolving the ETHs, while conservative treatment did not result in spontaneous resolution. Unresected meningioma around the trigone of the lateral ventricle is capable of causing the ETH, contrary to the notion that, infection or postoperative adhesions are the key causes of ETH. Thus, neurosurgeons ought to be on a lookout for ETH when treating lesions around the trigone area of the lateral ventricles.
FlapMap Visual Language System for Vascular Imaging Prior to Microvascular Free Tissue Transfer
Authors: Ibelli Taylor J. , Sayegh Farah , Kagen Alexander C. , Henderson Peter W.
Published: June 2022

Preoperative vascular imaging has been shown to be beneficial before free tissue transfer procedures, especially for deep inferior epigastric perforator flap breast reconstruction. Although computerized tomography angiography and magnetic resonance angiogram are increasingly frequently performed, there is no standardized method for recording, analyzing, and communicating the vast amount of clinically relevant information that is obtained from these tomographic imaging studies. Herein, the authors propose a new visual language system for preoperative imaging called “FlapMap,” which allows for the creation of a clinically actionable, easily understood, and easily communicated single image that aids in preoperative planning before microvascular free tissue transfer.
Predictors of older adults' chronic pain in the context of opioid adverse drug events
Authors: McDonald Deborah Dillon , Walsh Stephen J.
Published: June 2022

Background:

Factors predictive of chronic pain in older adults could help focus prevention and treatment efforts for those most at risk of chronic pain.

Purpose:

The objective of the study was to describe demographic and pain self-management factors predictive of chronic pain in the context of opioid adverse drug events (ADEs) reported for a cohort of older adults within the same year.

Method:

The design was a post hoc analysis of 9,095 cases aged 65 years and older from the 2019 National Health Interview Survey that reported chronic pain and 380 cases aged 65 years and older with opioid adverse events reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) during the second quarter of 2019. Logistic regression predicted chronic pain.

Results:

Less than a baccalaureate education increased the odds of chronic pain by 28.0% while lower income minimally increased the odds. Male gender increased the odds of chronic pain by 12.0%. Increased age minimally increased the odds for chronic pain. Use of opioids, other pain treatments, complementary treatments, and antidepressants were all associated with increased odds of chronic pain. FAERS opioid ADEs ranged from pruritus to death, with death identified in 16 (4.2%) cases. Misuse, abuse, or dependence was documented in 1.8% of cases.

Conclusions and Implications:

Less-educated older adults may be particularly at risk of chronic pain and should be routinely assessed and prescribed safe and efficacious pain self-management as needed. Some men may need additional support to use pain treatments.
The weaning from mechanical ventilation: a comprehensive ultrasound approach
Authors: Santangelo Erminio , Mongodi Silvia , Bouhemad Bélaid , Mojoli Francesco
Published: June 2022

Purpose of review

Due to heart, lung and diaphragm interactions during weaning from mechanical ventilation, an ultrasound integrated approach may be useful in the detection of dysfunctions potentially leading to weaning failure. In this review, we will summarize the most recent advances concerning the ultrasound applications relevant to the weaning from mechanical ventilation.

Recent findings

The role of ultrasonographic examination of heart, lung and diaphragm has been deeply investigated over the years. Most recent findings concern the ability of lung ultrasound in detecting weaning induced pulmonary edema during spontaneous breathing trial. Furthermore, in patients at high risk of cardiac impairments, global and anterolateral lung ultrasound scores have been correlated with weaning and extubation failure, whereas echocardiographic indexes were not. For diaphragmatic ultrasound evaluation, new indexes have been proposed for the evaluation of diaphragm performance during weaning, but further studies are needed to validate these results.

The present review summarizes the potential role of ultrasonography in the weaning process. A multimodal integrated approach allows the clinician to comprehend the pathophysiological processes of weaning failure.
Temperature control after cardiac arrest: friend or foe
Authors: Nolan Jerry P. , Soar Jasmeet
Published: June 2022

Purpose of review

Most patients who are successfully resuscitated after cardiac arrest are initially comatose and require mechanical ventilation and other organ support in an ICU. Best practice has been to cool these patients and control their temperature at a constant value in the range of 32–36 oC for at least 24 h. But the certainty of the evidence for this practice is increasingly being challenged. This review will summarize the evidence on key aspects of temperature control in comatose postcardiac arrest patients.

Recent findings

The Targeted Temperature Management 2 (TTM-2) trial documented no difference in 6-month mortality among comatose postcardiac arrest patients managed at 33 oC vs. targeted normothermia. A systematic review and meta-analysis completed by the Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR) concluded that temperature control with a target of 32–34 °C did not improve survival or favourable functional outcome after cardiac arrest. Two observational studies have documented an association between predicted moderate hypoxic–ischaemic brain injury and better outcome with temperature control at 33–34 oC compared with 35–36 oC.

We suggest actively preventing fever by targeting a temperature 37.5 oC or less for those patients who remain comatose following return of spontaneous circulation (ROSC) after cardiac arrest.
New developments in the understanding of right ventricular function in acute care
Authors: Couture Etienne J. , Grønlykke Lars , Denault André Y.
Published: June 2022

Purpose of review

Right ventricular dysfunction has an important impact on the perioperative course of cardiac surgery patients. Recent advances in the detection and monitoring of perioperative right ventricular dysfunction will be reviewed here.

Recent findings

The incidence of right ventricular dysfunction in cardiac surgery has been associated with unfavorable outcomes. New evidence supports the use of a pulmonary artery catheter in cardiogenic shock. The possibility to directly measure right ventricular pressure by transducing the pacing port has expanded its use to track changes in right ventricular function and to detect right ventricular outflow tract obstruction. The potential role of myocardial deformation imaging has been raised to detect patients at risk of postoperative complications.

Perioperative right ventricular function monitoring is based on echocardiographic and extra-cardiac flow evaluation. In addition to imaging modalities, hemodynamic evaluation using various types of pulmonary artery catheters can be achieved to track changes rapidly and quantitatively in right ventricular function perioperatively. These monitoring techniques can be applied during and after surgery to increase the detection rate of right ventricular dysfunction. All this to improve the treatment of patients presenting early signs of right ventricular dysfunction before systemic organ dysfunction ensue.
Vomiting and Gastric Motility in Early Brain Damaged Children With Congenital Zika Syndrome
Authors: de Paula Georgia Lima , da Silva Giselia Alves Pontes , e Silva Eduardo Just da Costa , Lins Maria das Graças Moura , Martins Olga Sophia de Sousa , Oliveira Danielle Maria da Silva , Ferreira Eric de Santana , Antunes Margarida Maria de Castro
Published: June 2022

Objectives:

This study investigated the occurrence of vomiting and gastric dysmotility in dysphagic children with congenital Zika syndrome (CZS) and assessed possible associations of these findings with the severity of dysphagia and the presence of tube feeding.

Methods:

Forty-six children with CZS were assessed for dysphagia, and the occurrence of vomiting, dietary volume tolerance <15 mL/kg, and feeding time per meal >30 minutes were evaluated. Gastric antrum ultrasonography was used to detect the frequency of contractions and measure antral areas (at fasting and 15 minutes postprandial), from which the gastric emptying rate (GER) was calculated. Antral ultrasonography findings were compared with those of ten healthy controls. Vomiting and gastric motility were compared between CZS patients according to the severity of dysphagia and the requirement for tube feeding.

Results:

Overall, 76% (35/46) of children with CZS had moderate-to-severe dysphagia (MSD), among whom 60% (21/35) were tube fed [MSD tube fed (MSDTF)]. Vomiting occurred in 54% (25/46) of children, whereas dietary volume intolerance and prolonged feeding time were observed in 59% (27/46) and 37% (17/46), respectively, most frequently in MSDTF patients. On ultrasound, 61% (28/46) of children with CZS had no antral contractions, whereas 90% (9/10) of controls did. Compared to healthy controls, GER was eight-fold lower in children with CZS and 60-fold lower in MSDTF children.

Conclusions:

In dysphagic children with CZS, vomiting, volume intolerance, and prolonged feeding time were frequent and possibly associated with impaired antral contraction and delayed gastric emptying, especially in cases of severe dysphagia and tube feeding.
The Use of the Consolidated Framework for Implementation Research to Understand Facilitators and Barriers to Sexually Transmitted Infection Screening in Primary Care
Authors: Ahmad Fahd A. , Dickey Viani , Tetteh Emmanuel K. , Foraker Randi , McKay Virginia R.
Published: June 2022

Background

Adolescents bear a disproportionate burden of sexually transmitted infections (STIs) and the sequelae of delayed treatment, yet STI screening is infrequently performed in pediatric primary care clinics with many of those at-risk not administered testing. This study aims to understand contextual factors influencing STI screening and testing among adolescents in pediatric primary care.

Methods

We used the Consolidated Framework for Implementation Research (CFIR) as part of a stepwise approach to facilitate a deep understanding the pediatric primary care environment. We conducted semistructured interviews of physicians, nurses, and patient-parent dyads from 4 pediatric primary care practices in the St. Louis metropolitan area about STI screening practices and common concerns regarding STI screening. Qualitative analysis was conducted using a categorical coding technique informed by the CFIR followed by a thematic coding technique.

Results

We interviewed 23 physicians/nurses and 12 patient-parent dyads. Individual-level barriers to STI screening and testing included wide variability in clinicians' practice patterns and their perception of STI risk in the patient population. Structural barriers included a lack of capacity to perform testing in clinic and time constraints during patient visits. Confidentiality issues also created significant barriers to screening and testing on both individual and structural levels. Adopting confidential methods for testing and educating providers on patients' recommendations for STI testing were discussed as ways to potentially improve STI care in pediatric patients.

Conclusions

Our use of the CFIR facilitated a systematic approach to identify gaps in STI care for adolescents and identified opportunities to close those gaps. An integrated, systematic approach that enhances patient confidentiality and improves clinicians' knowledge could address gaps in STI care in pediatric primary care settings.
GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics
Authors: Toland Angus M.S. , Lam Suk Wai , Varma Sushama , Wang Aihui , Howitt Brooke E. , Kunder Christian A. , Kerr Darcy A. , Szuhai Karoly , Bovée Judith V.M.G. , Charville Gregory W.
Published: June 2022

Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm that manifests histologically as a lobular proliferation of stellate to spindle-shaped cells in a myxoid background, exhibiting morphologic overlap with other cartilaginous and myxoid tumors of bone. CMF is characterized by recurrent genetic rearrangements that place the glutamate receptor gene GRM1 under the regulatory control of a constitutively active promoter, leading to increased gene expression. Here, we explore the diagnostic utility of GRM1 immunohistochemistry as a surrogate marker for GRM1 rearrangement using a commercially available monoclonal antibody in a study of 230 tumors, including 30 CMF cases represented by 35 specimens. GRM1 was positive by immunohistochemistry in 97% of CMF specimens (34/35), exhibiting moderate to strong staining in more than 50% of neoplastic cells; staining was diffuse (>95% of cells) in 25 specimens (71%). Among the 9 CMF specimens with documented exposure to acid decalcification, 4 (44%) exhibited diffuse immunoreactivity (>95%) for GRM1, whereas all 15 CMF specimens (100%) with lack of exposure to decalcification reagents were diffusely immunoreactive (P=0.003). High GRM1 expression at the RNA level was previously observed by quantitative reverse transcription polymerase chain reaction in 9 CMF cases that were also positive by immunohistochemistry; low GRM1 expression was observed by quantitative reverse transcription polymerase chain reaction in the single case of CMF that was negative by immunohistochemistry. GRM1 immunohistochemistry was negative (<5%) in histologic mimics of CMF, including conventional chondrosarcoma, enchondroma, chondroblastoma, clear cell chondrosarcoma, giant cell tumor of the bone, fibrous dysplasia, chondroblastic osteosarcoma, myoepithelial tumor, primary aneurysmal bone cyst, brown tumor, phosphaturic mesenchymal tumor, CMF-like osteosarcoma, and extraskeletal myxoid chondrosarcoma. These results indicate that GRM1 immunohistochemistry may have utility in distinguishing CMF from its histologic mimics.
Predictors of adverse pregnancy outcomes among Kenyan women with HIV on antiretroviral treatment in pregnancy
Authors: Jiang Wenwen , Ronen Keshet , Osborn Lusi , Drake Alison L. , Unger Jennifer A. , Matemo Daniel , Enquobahrie Daniel A. , Kinuthia John , John-Stewart Grace
Published: June 2022

Objective:

The aim of this study was to understand predictors of adverse pregnancy outcomes (APOs) among women on antiretroviral treatment (ART).

Design:

A longitudinal cohort

Methods:

Participants from the Mobile WAChX trial were evaluated for APOs, including stillbirth (fetal death at ≥20 weeks’ gestation), preterm birth (PTB, livebirth at <37 weeks’ gestation,) and neonatal death (NND, ≤28 days after live birth). Predictors were determined by univariable and multivariable Cox proportional hazards and log-binomial models.

Results:

Among 774 women included, median age was 27 years and 29.0% had unsuppressed HIV viral load (>1000 copies/ml) at enrollment. Half (55.1%) started ART prepregnancy, 89.1% on tenofovir-based regimens. Women with depression had a higher risk of stillbirth (adjusted hazard ratio [aHR] 2.93, 95% confidence interval (95% CI) 1.04–8.23), and women with lower social support score had higher risk of late stillbirth (aHR 11.74, 2.47–55.86). Among 740 livebirths, 201 (27.2%) were preterm and 22 (3.0%) experienced NND. PTB was associated with unsuppressed maternal viral load (adjusted prevalence ratio [aPR] 1.28, 95% CI 1.02–1.61), intimate partner violence (IPV) in pregnancy (aPR 1.94, 95% CI 1.28–2.94), and history of any sexually transmitted infection (STI) (aPR 1.63, 95% CI 1.06–2.51). NND was associated with PTB (aPR 2.53, 95% CI 1.10–5.78) and STI history (aPR 4.25, 95% CI 1.39–13.06). Most associations retained significance in the subgroup of women with viral suppression.

Conclusion:

Maternal viremia during pregnancy predicted PTB as did IPV, lower education, and STI history, while psychosocial stressors predicted stillbirth. Implementing mental health services, ART adherence, partner support, and routine STI screening and treatment could reduce APOs among women with HIV in sub-Saharan Africa settings.
The Utility of Submucosal Linear Enhancement on Dynamic Computed Tomography for Patients With Internal Hemorrhoids
Authors: Kisaki Shunsuke , Igarashi Takao , Ashida Hirokazu , Furuhashi Hiroto , Ojiri Hiroya
Published: June 2022

Objective

The purpose of this study was to evaluate the utility of submucosal linear enhancement on dynamic computed tomography (CT) for patients with internal hemorrhoids.

Methods

We retrospectively reviewed patients who were admitted to our institution due to acute lower gastrointestinal bleeding and underwent both dynamic CT and colonoscopy. The presence of submucosal linear enhancement of the intestinal wall from the lower rectum to the anal canal was evaluated using arterial-phase CT images. Based on these images, patients were then classified into 2 groups by 2 blinded radiologists, as follows: group A (absence of submucosal linear enhancement) and group B (presence of submucosal linear enhancement). The relationship between the groups and the risk of bleeding in internal hemorrhoids was evaluated using the size and range of internal hemorrhoids measured during colonoscopy as reference standards.

Results

A total of 94 patients were reviewed; of these, 62 patients without submucosal linear enhancement were classified into group A, and 32 patients with submucosal linear enhancement were classified into group B. Group B showed a significantly greater range (P = 0.017) and size (P = 0.002) of internal hemorrhoids. The Cohen κ coefficient value for the group classifications between the 2 radiologists was 0.66.

Conclusions

Submucosal linear enhancement on arterial-phase CT images could be a predictive finding suggesting the presence of internal hemorrhoids with a high risk of bleeding.
E-cigarette use and Respiratory Symptoms in Residents of the United States: A BRFSS Report
Authors: Varella Marcia H. , Andrade Olyn A. , Shaffer Sydney M. , Castro Grettel , Rodriguez Pura , Barengo Noël C. , Acuna Juan M.
Published: June 2022

Purpose

E-cigarettes are the most common type of electronic nicotine delivery system in the United States, rapidly gaining presence worldwide. E-cigarettes contain numerous toxic compounds that have been shown to induce mild to severe structural damage to the airways. The objective of this study is to assess if there is an association between e-cigarette use and respiratory symptoms in adults in the US as reported in the BRFSS in an attempt to drive potential early detection and prevention of severe or permanent respiratory disease.

Methods

We analyzed data from 18,079 adults, 18-44 years, who participated at the Behavioral Risk Factor Surveillance System (BRFSS) in the year 2017. E-cigarette smoking status was categorized as current everyday user, current some days user, former smoker, and never smoker. The frequency of any respiratory symptoms (cough, phlegm, or shortness of breath) was compared. We calculated unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI).

Results

The BRFSS reported prevalence of smoking e-cigarettes was 6%. About 28% of the participants reported any of the respiratory symptoms assessed. The frequency of reported respiratory symptoms was highest among current some days e-cigarette users (45%). After adjusting for selected participant’s demographic, socio-economic, and behavioral characteristics, and asthma and COPD status, the odds of reporting respiratory symptoms increased by 49% among those who use e-cigarettes some days (OR 1.49; 95% CI: 1.06-2.11), and by 29% among those who were former users (OR 1.29; 95% CI: 1.07-1.55) compared with those who never used e-cigarettes. No statistically significant association was found for those who used e-cigarettes every day (OR 1.41; 95% CI 0.96-2.08)

Conclusion

E-cigarettes cannot be considered safe alternatives to combustible traditional cigarettes. Cohort studies may shed more evidence on the association between e-cigarette use and specific respiratory diseases.
Investigating the use and effectiveness of lifestyle medicine approaches to tackle erectile dysfunction: a cross-sectional eSurvey based study
Authors: El-Osta Austen , Kerr Gabriele , Alaa Aos , El Asmar Marie Line , Karki Manisha , Webber Iman , Sasco Eva Riboli , Blume Giordano , Beecken Wolf-D. , Mummery David
Published: June 2022

Background

Erectile dysfunction (ED) is the most common sexual dysfunction in men. Some types of ED are amenable to treatment using lifestyle medicine approaches with or without pharmacotherapy.

Aim

Investigate the use and perceived effectiveness of lifestyle medicine approaches to tackle ED.

Methods

A cross-sectional online survey of 1177 community dwelling adults explored the prevalence and methods used to tackle ED in the community setting. We examined differences between participants with and without ED. Variables associated with ED in univariable analyses were included in a multivariable logistic regression to identify variables independently associated with the condition.

Outcomes

Self-reported measure; perceived effectiveness of lifestyle medicine interventions to tackle ED

Results

Most respondents (76.5%) had experienced ED, and this was associated with having a long-term condition, taking anti-hypertensive medication, hypercholesterolaemia and obesity. Medication was the most common management strategy overall (65.9%), followed by stress management (43.5%) and weight loss (40.4%). Over half (53.9%) did not use any lifestyle modification strategies to tackle ED. Only 7.0% of ED sufferers received a mental health assessment and 29.2% received other tests (e.g., blood test, medical imaging) by GPs. Cardiovascular training was identified as the best rated strategy by its users (37.8%). Supplements (35.1%) and weight training/physical activity (32.6%) were also positively rated.

Clinical implications

Structured education to general practitioners and community dwelling adults about the impact of lifestyle behaviour modification and how this could influence the appearance or trajectory of ED could help improve personal choice when tackling ED.

Strengths and Limitations

To our knowledge, this is the first study to collect eSurvey responses from community dwelling adults to gauge their reliance and perceived effectiveness of lifestyle medicine approaches to tackle ED. The principal limitation was the lack of follow-up, and not recording other information including lifestyle factors such as nutrition, smoking, and the use of alcohol and recreational drugs, which may have enabled a fuller exploration of the factors that could influence the primary outcome measures examined.

Conclusion

Despite the high prevalence of ED, there is not enough awareness in the community setting about effective and low-cost lifestyle medicine strategies, including cardiovascular training and the use of supplements and weight training, to help tackle this common condition
Application of machine learning and complex network measures to an EEG dataset from ayahuasca experiments
Authors: Alves Caroline L. , Cury Rubens Gisbert , Roster Kirstin , Pineda Aruane M. , Rodrigues Francisco A. , Thielemann Christiane , Ciba Manuel
Published: June 2022

Ayahuasca is made from a mixture of Amazonian herbs and has been used for a few hundred years by the people of this region for traditional medicine. In addition, this plant has been shown to be a potential treatment for various neurological and psychiatric disorders.

EEG experiments have found specific brain regions that changed significantly due to ayahuasca. Here, we used an EEG dataset to investigate the ability to automatically detect changes in brain activity using machine learning and complex networks. Machine learning was applied at three different levels of data abstraction: (A) the raw EEG time series, (B) the correlation of the EEG time series, and (C) the complex network measures calculated from (B).

As a result, the machine learning method was able to automatically detect changes in brain activity, with case (B) showing the highest accuracy (92%), followed by (A) (88%) and (C) (83%), indicating that connectivity changes between brain regions are more important than connectivity changes within brain regions. The most activated areas were the frontal and temporal lobe, which is consistent with the literature.

In terms of brain connections, the correlation between F3 and PO4 was the most important. This connection may point to a cognitive process similar to face recognition in individuals during ayahuasca-mediated visual hallucinations.

Furthermore, closeness centrality and assortativity were the most important complex network measures. These two measures are also associated with diseases such as Alzheimer’s disease, indicating a possible therapeutic mechanism.

Overall, our results showed that machine learning methods were able to automatically detect changes in brain activity during ayahuasca consumption. The results also suggest that the application of machine learning and complex network measurements are useful methods to study the effects of ayahuasca on brain activity and medical use.
Mast cells impair melanoma cell homing and metastasis by inhibiting HMGA1 secretion
Authors: Benito-Martin Alberto , Hergueta-Redondo Marta , Nogués Laura , Castellano-Sanz Elena , Garvin Eduardo , Cioffi Michele , Sola-Castrillo Paloma , Buehring Weston , Ximénez-Embún Pilar , Muñoz Javier , Matei Irina , Villanueva Josep , Peinado Héctor
Published: June 2022

Metastatic disease is the major cause of death from cancer. From the primary tumor, cells remotely prepare the environment of the future metastatic sites by secreted factors and extracellular vesicles. During this process, known as pre-metastatic niche formation, immune cells play a crucial role. Mast cells are hematopoietic bone marrow-derived innate immune cells whose function in lung immune response to invading tumors remains to be defined. We found reduced melanoma lung metastasis in mast cell deficient mouse models (Wsh and MCTP5-Cre-RDTR), supporting a pro-metastatic role for mast cells in vivo. However, due to evidence pointing to their antitumorigenic role, we studied the impact of mast cells in melanoma cell function in vitro. Surprisingly, in vitro co-culture of bone-marrow derived mast cells with melanoma cells showed that they have an intrinsic anti-metastatic activity. Mass spectrometry analysis of melanoma-mast cell co-cultures secretome showed that HMGA1 secretion by melanoma cells was significantly impaired. Consistently, HMGA1 knock down in B16-F10 cells reduced their metastatic capacity in vivo. Importantly, analysis of HMGA1 expression in human melanoma tumors showed that metastatic tumors with high HMGA1 expression are associated with reduced overall and disease-free survival. Moreover, we show that HMGA1 is reduced in the nuclei and enriched in the cytoplasm of melanoma metastatic lesions when compared to primary tumors. These data suggest that high HMGA1 expression and secretion from melanoma cells promotes metastatic behavior. Targeting HMGA1 expression intrinsically or extrinsically by mast cells actions reduce melanoma metastasis. Our results pave the way to the use of HMGA1 as anti-metastatic target in melanoma as previously suggested in other cancer types.
The lupus susceptibility alleleDRB1*03:01encodes a disease-driving epitope
Authors: Scavuzzi Bruna Miglioranza , van Drongelen Vincent , Kaur Bhavneet , Fox Jennifer Callahan , Liu Jianhua , Mesquita-Ferrari Raquel A. , Kahlenberg J. Michelle , Farkash Evan A. , Benavides Fernando , Miller Frederick W. , Sawalha Amr H. , Holoshitz Joseph
Published: June 2022

TheHLA-DRB1*03:01allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a shortDRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïveDRB1*03:01transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble human lupus nephritis. This study provides evidence for a noncanonical, antigen presentation-independent mechanism of HLA-disease association in SLE and could lay new foundations for our understanding of key molecular mechanisms that trigger and propagate this devastating autoimmune disease.
A remodeled RNA polymerase II complex catalyzing viroid RNA-templated transcription
Authors: Dissanayaka Mudiyanselage Shachinthaka D. , Ma Junfei , Pechan Tibor , Pechanova Olga , Liu Bin , Wang Ying
Published: June 2022

Viroids, a group of plant pathogens, are mysterious subviral agents composed of single-stranded circular noncoding RNAs. Nuclear-replicating viroids exploit host RNA polymerase II (Pol II) activity for transcription from circular RNA genome to minus-strand intermediates, a classic example illustrating the intrinsic RNA-dependent RNA polymerase activity of Pol II. The mechanism for Pol II to accept single-stranded RNAs as templates for transcription remains poorly understood. Here, we reconstituted a robust in vitro transcription system and demonstrated that Pol II also accepts the minus-strand viroid RNA template to generate plus-strand RNAs. Based on this reconstituted system, we purified the Pol II complex on RNA templates for nano-liquid chromatography-tandem mass spectrometry analysis. We identified a remodeled Pol II missing Rpb4, Rpb5, Rpb6, Rpb7, and Rpb9, which contrasts to the canonical 12-subunit Pol II or the 10-subunit Pol II core on DNA templates. This remodeled Pol II is active in transcription with the aid of TFIIIA-7ZF. Interestingly, this remodeled Pol II appears not to require other canonical general transcription factors (such as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and TFIIS), indicating a different mechanism/machinery regulating RNA-templated transcription. Transcription elongation factors, such as FACT complex, PAF1 complex, and SPT6, were also absent in the transcription complex on RNA templates. We further analyzed the critical zinc finger domains in TFIIIA-7ZF for aiding Pol II activity on RNA template and revealed the first three zinc finger domains pivotal for template binding. Collectively, our data illustrated a distinct organization of Pol II complex on viroid RNA templates, providing new insights into the evolution of transcription machinery, the mechanism of RNA-templated transcription, as well as viroid replication.
Nuclear position modulates long-range chromatin interactions
Authors: Finn Elizabeth H. , Misteli Tom
Published: June 2022

The human genome is non-randomly organized within the cell nucleus. Spatial mapping of genome folding by biochemical methods and imaging has revealed extensive variation in locus interaction frequencies between cells in a population and between homologs within an individual cell. Commonly used mapping approaches typically examine either the relative position of genomic sites to each other or the position of individual loci relative to nuclear landmarks. Whether the frequency of specific chromatin-chromatin interactions is affected by where in the nuclear space a locus is located is unknown. Here, we have simultaneously mapped at the single cell level the interaction frequencies and radial position of more than a hundred locus pairs using high-throughput imaging to ask whether the location within the nucleus affects interactions frequency. We find strong enrichment of many interactions at specific radial positions. Position-dependency of interactions was cell-type specific, correlated with local chromatin type, and cell-type-specific enriched associations were marked by increased variability, sometimes without a significant decrease in mean spatial distance. These observations demonstrate that genome organization relative to itself and relative to nuclear landmarks are closely interwoven.

Significance Statement

A gene’s nuclear environment is defined by its distance to other genes as well as its distance to nuclear structures such as the nuclear periphery. While both of these features have been shown to be important for gene function, they are often studied separately. We performed the first systematic analysis comparing these two features. We determined that at the level of single chromosomes they are correlated, suggesting that genome organization relative to itself and relative to nuclear landmarks are closely interwoven.
Mechanism of PEX5-mediated protein import into peroxisomes
Authors: Skowyra Michael L. , Rapoport Tom A.
Published: June 2022

Peroxisomes are ubiquitous organelles, whose dysfunction causes fatal human diseases. Most peroxisomal enzymes are imported from the cytosol by the receptor PEX5, which interacts with a docking complex in the peroxisomal membrane, and then returns to the cytosol after monoubiquitination by a membrane-embedded ubiquitin ligase. The mechanism by which PEX5 shuttles between cytosol and peroxisomes, and releases cargo inside the lumen, is unclear. Here, we use Xenopus egg extract to demonstrate that PEX5 accompanies cargo completely into the lumen, utilizing WxxxF/Y motifs near its N-terminus that bind a lumenal domain of the docking complex. PEX5 recycling is initiated by an amphipathic helix that binds to the lumenal side of the ubiquitin ligase. The N-terminus then emerges in the cytosol for monoubiquitination. Finally, PEX5 is extracted from the lumen, resulting in unfolding of the receptor and cargo release. Our results reveal the unique mechanism by which PEX5 ferries proteins into peroxisomes.
Reconstitution of an N-AChR from Brugia malayi
Authors: Noonan Jennifer D. , Beech Robin N.
Published: June 2022

Neurotransmission is an important target for anthelmintic drugs, where receptor characteristics and response can be examined through reconstitution ex vivo in Xenopus laevis oocytes. The homomeric ACR-16 nicotine sensitive acetylcholine receptors (N-AChRs) of several helminth species have been characterized in this way. Our efforts to reconstitute the N-AChR from the clade III filarial parasite, Brugia malayi using similar conditions, initially produced no detectable response. A robust response to acetylcholine is obtained from the closely related clade III parasite Ascaris suum, suggesting that specific changes have occurred between Ascaris and Brugia. N-AChRs from three species intermediate between A. suum and B. malayi were characterized to provide information on the cause. Maximal current to acetylcholine did not change abruptly, consistent with a discrete event, but rather decreased progressively from A. suum through Dracunculus medinensis, Gonglylonema pulchrum and Thelazia callipaeda. Receptor responses to the characteristic nicotine, and other agonists were generally similar. The decrease in maximal current did correlate with a delayed time to maximal response. Together, this suggested that the failure to reconstitute the B. malayi N-AChR was one extreme of a progressive decrease and that synthesis of the receptor in oocytes was responsible. Addition of accessory proteins EMC-6, NRA-2 and NRA-4, in addition to RIC-3, produced a small, but measurable B. malayi N-AChR response. Pharmacological properties of a chimeric B. malayi N-AChR were equivalent to the other species, confirming the receptor response remains unchanged while its production is increasingly dependent on accessory proteins. One possibility is that loss of many subunits for acetylcholine receptors from the filarial nematode genome is linked to such a dependence. This novel phylogenetic approach allowed the first characterization of a B. malayi AChR ex vivo and in doing so, provides a framework for the successful characterization of other receptors that have yet to be reconstituted.
Opto-MASS: a high-throughput engineering platform for genetically encoded fluorescent sensors enabling all-optical in vivo detection of monoamines and opioids
Authors: Rappleye Michael , Gordon-Fennel Adam , Castro Daniel C. , Matarasso Avi K. , Zamorano Catalina A. , Stine Carrie , Wait Sarah J. , Lee Justin D. , Siebart Jamison C. , Suko Azra , Smith Netta , Muster Jeanot , Matreyek Kenneth A , Fowler Douglas M. , Stuber Garrett D. , Bruchas Michael R. , Berndt Andre
Published: June 2022

Fluorescent sensor proteins are instrumental for detecting biological signals in vivo with high temporal accuracy and cell-type specificity. However, engineering sensors with physiological ligand sensitivity and selectivity is difficult because they need to be optimized through individual mutagenesis in vitro to assess their performance. The vast mutational landscape proteins constitute an obstacle that slows down sensor development. This is particularly true for sensors that require mammalian host systems to be screened. Here, we developed a novel high-throughput engineering platform that functionally tests thousands of variants simultaneously in mammalian cells and thus allows the screening of large variant numbers. We showcase the capabilities of our platform, called Optogenetic Microwell Array Screening System (Opto-MASS), by engineering novel monoamine and neuropeptide in vivo capable sensors with distinct physiological roles at high-throughput.
SUBATOMIC: a SUbgraph BAsed mulTi-OMIcs Clustering framework to analyze integrated multi-edge networks
Authors: Loers Jens Uwe , Vermeirssen Vanessa
Published: June 2022

Representing the complex interplay between different types of biomolecules across different omics layers in multi-omics networks bears great potential to gain a deep mechanistic understanding of gene regulation and disease. However, multi-omics networks easily grow into giant hairball structures that hamper biological interpretation. Module detection methods can decompose these networks into smaller interpretable modules. However, these methods are not adapted to deal with multi-omics data nor consider topological features. When deriving very large modules or ignoring the broader network context, interpretability remains limited. To address these issues, we developed a subgraph based multi-omics clustering framework (SUBATOMIC), which infers small and interpretable modules with a specific topology while keeping track of connections to other modules and regulators.

SUBATOMIC groups specific molecular interactions in composite network subgraphs of two and three nodes and clusters them into topological modules. These are functionally annotated, visualized and overlaid with expression profiles to go from static to dynamic modules. To preserve the larger network context, SUBATOMIC investigates statistically the connections in between modules as well as between modules and regulators such as miRNAs and transcription factors. We applied SUBATOMIC to analyze a composite Homo sapiens network containing transcription factor-target gene, miRNA-target gene, protein-protein, homologous and co-functional interactions from different databases. We derived and annotated 5586 modules with diverse topological, functional and regulatory properties. We created novel functional hypotheses for unannotated genes. Furthermore, we integrated modules with condition specific expression data to study the influence of hypoxia in three cancer cell lines. We developed two prioritization strategies to identify the most relevant modules in specific biological contexts: one considering GO term enrichments and one calculating an activity score reflecting the degree of differential expression. Both strategies yielded modules specifically reacting to low oxygen levels.

In conclusion, we developed the SUBATOMIC framework that generates interpretable modules from multi-omics networks and applied it to hypoxia in cancer. SUBATOMIC can infer and contextualize modules, explore condition or disease specific modules, identify regulators and functionally related modules, and derive novel gene functions for uncharacterized genes. The software is available at https://github.com/CBIGR/SUBATOMIC.