bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the potential relationships among obstructive sleep apnea, erectile dysfunction, and gut microbiota: a narrative review
Authors: Andersen Monica Levy , Gozal David , Pires Gabriel Natan , Tufik Sergio
Published: June 2023

Introduction

Poor sleep quality is closely associated with comorbidities affecting a multitude of organ systems. Among the sleep disorders in the population, there has recently been an increase in the prevalence of obstructive sleep apnea (OSA), which has particularly affected men. The intermittent hypoxia and sleep fragmentation associated with OSA can result in the manifestation or aggravation of a number of pathophysiologic conditions, including the impairment of reproductive function in men and women. In this context, erectile dysfunction (ED) is of particular concern. Other consequences of OSA are changes in the gastrointestinal microbiota, with the resultant dysbiosis having potentially harmful consequences that promote downstream exacerbation of various comorbidities.

Objectives

This narrative review aims to explore the potential relationships among ED, gut microbiota, and OSA.

Methods

A search of the relevant literature was performed in the PubMed, Embase, Medline, and Web of Science databases.

Results

Sleep is important for regulating the body’s functions, and sleep deprivation can negatively affect health. OSA can damage organic functions, including reproductive function, and can lead to ED. Restoring the microbiota and improving sleep can help to improve sexual function or reverse ED and enhance other associated conditions mediated through the gut-brain axis relationship. Probiotics and prebiotics can be used as supportive strategies in the prevention and treatment of OSA, as they help to reduce systemic inflammation and improve intestinal barrier function.

Conclusion

A good diet, a healthy lifestyle, and proper bowel function are essential in controlling depression and several other pathologies. Modulating the gut microbiota through probiotics and prebiotics can provide a viable strategy for developing new therapeutic options in treating many conditions. A better understanding of these a priori unrelated phenomena would foster our understanding of the effects of OSA on human fertility and how changes in gut microbiota may play a role.
Overexpression of PsAMT1.2 in poplar enhances nitrogen utilization and resistance to drought stress
Authors: Zhang Chunxia , Li Yang , Yang Tianli , Shi Mengting
Published: June 2023

Ammonium is an important form of inorganic nitrogen, which is essential for plant growth and development, and the uptake of ammonium is mediated by different members of ammonium transporters (AMTs). It is reported that PsAMT1.2 is specially expressed in the root of poplar, and the overexpression of PsAMT1.2 could improve plant growth and the salt tolerance of poplar. However, the role of AMTs in plant drought and low nitrogen (LN) resistance remains unclear. To understand the role of PsAMT1.2 in drought and LN tolerance, the response of PsAMT1.2-overexpression poplar to polyethylene glycol (PEG)-simulated drought stress (5% PEG) under LN (0.001 mM NH4NO3) and moderate nitrogen (0.5 mM NH4NO3) conditions was investigated. The PsAMT1.2-overexpression poplar showed better growth with increased stem increment, net photosynthetic rate, chlorophyll content, root length, root area, average root diameter and root volume under drought and/or LN stress compared with the wild type (WT). Meanwhile, the content of malondialdehyde significantly decreased, and the activities of superoxide dismutase and catalase significantly increased in the roots and leaves of PsAMT1.2-overexpression poplar compared with WT. The content of NH4+ and NO2− in the roots and leaves of PsAMT1.2-overexpression poplar was increased, and nitrogen metabolism–related genes, such as GS1.3, GS2, Fd-GOGAT and NADH-GOGAT, were significantly upregulated in the roots and/or leaves of PsAMT1.2-overexpression poplar compared with WT under drought and LN stress. The result of this study would be helpful for understanding the function of PsAMT1.2 in plant drought and LN tolerance and also provides a new insight into improving the drought and LN tolerance of Populus at the molecular level.
Loss of NOR‐1 represses muscle metabolism through mTORC1‐mediated signaling and mitochondrial gene expression in C2C12 myotubes
Authors: Paez Hector G. , Ferrandi Peter J. , Pitzer Christopher R. , Mohamed Junaith S. , Alway Stephen E.
Published: June 2023

Gene expression of the NR4A nuclear orphan receptor NOR‐1 is reduced in obesity and in human skeletal muscle during disuse. It has been well established that NOR‐1 is highly responsive to both aerobic and resistance exercise and NOR‐1 overexpression is coincident with a plethora of metabolic benefits. However, it is unclear whether loss of NOR‐1 contributes to inappropriate metabolic signaling in skeletal muscle that could lead to insulin resistance. The purpose of this study was to elucidate the impact of NOR‐1 deficiency on C2C12 metabolic signaling. Changes in gene expression after siRNA‐mediated NOR‐1 knockdown in C2C12 myotubes were determined by qPCR and bioinformatic analysis of RNA‐Seq data. Our RNA‐Seq data identified several metabolic targets regulated by NOR‐1 and implicates NOR‐1 as a modulator of mTORC1 signaling via Akt‐independent mechanisms. Furthermore, pathway analysis revealed NOR‐1 knockdown perturbs the insulin resistance and insulin sensitivity pathways. Taken together, these data suggest skeletal muscle NOR‐1 deficiency may contribute to altered metabolic signaling that is consistent with metabolic disease. We postulate that strategies that improve NOR‐1 may be important to offset the negative impact that inactivity, obesity, and type 2 diabetes have on mitochondria and muscle metabolism.
Photography and Image Acquisition in Dermatology a Scoping Review: Techniques for High-Quality Photography
Authors: Kashetsky Nadia , Mar Kristie , Liu Chaocheng , Rivers Jason K. , Mukovozov Ilya
Published: June 2023

BACKGROUND

Clinical photography is essential in dermatology, in particular in the areas of surgical and cosmetic dermatology and has been evolving rapidly. However, many dermatologists desire more training in clinical photography and a comprehensive literature review of photography in dermatology is lacking.

OBJECTIVE

This scoping review aimed to summarize the literature regarding techniques for high-quality photography in dermatology.

MATERIALS AND METHODS

A literature search was conducted using Embase, MEDLINE, PubMed, and Evidence-Based Medicine databases in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews.

RESULTS

This review summarizes information from 74 studies. Camera type, resolution, lens choice, camera settings, environment and set-up, standardization, and types of clinical photography are all important factors in acquisition of high-quality photography.

CONCLUSION

Photography in dermatology is continuously evolving with broader applications. Improved practices and innovations will benefit the quality of images.
Intradermal Delivery of Alopecia Therapeutics: Current State and Future Prospects
Authors: Alhanshali Lina , Buontempo Michael , Majerson Daniela , Shapiro Jerry , Lo Sicco Kristen
Published: June 2023

BACKGROUND

Mesotherapy, a technique of transdermal microinjections of specific preparations, is increasingly used in fields such as dermatology and specifically for alopecia treatment. Its popularity stems from its ability to deliver drugs in a targeted manner while minimizing systemic side effects.

OBJECTIVE

To assess and review current knowledge regarding the use of mesotherapy to deliver alopecia medications and highlight future directions for research.

MATERIALS AND METHODS

The authors used research databases including PubMed and Google Scholar to identify current literature on mesotherapy and alopecia. The following search terms were used among other terms: “Mesotherapy” or “Intradermal” AND “Alopecia”.

RESULTS

Recent studies are promising for the intradermal delivery of dutasteride and minoxidil in the treatment of androgenetic alopecia.

CONCLUSION

Although limitations exist with dutasteride and minoxidil therapies, further research regarding the preparation, delivery, and maintenance of these drugs is warranted as mesotherapy could establish this technique as a safe, effective, and viable treatment option for androgenetic alopecia.
Update on antiadhesion barriers and therapeutics in gynecological surgery
Authors: Dawodu Olanrewaju , Baxter Briana , Kim Jin Hee
Published: June 2023

Purpose of review

Postoperative adhesions remain a clinical challenge to both patients and providers, as they are associated with significant complications and a high economic burden. This article provides a clinical review of currently available antiadhesive agents and promising new therapies that have advanced past animal studies.

Recent findings

Several agents have been investigated on their ability to reduce adhesion formation; however, there is no widely acceptable option. The few available interventions are barrier agents and while low-quality evidence suggests that they may be more effective than no treatment, there is no general agreement on their overall efficacy. There is an abundance of research on new solutions; however, their clinical efficacy is yet to be determined.

Although a wide range of therapeutics have been investigated, majority are halted in animal models with only a select few being studied in humans and ultimately available in the market. Many agents have shown effectiveness in reducing adhesion formation, however, that has not been translated to improvement in clinically relevant outcomes; hence the need for high-quality large randomized trials.
An update and review of nontubal ectopic pregnancy management
Authors: Kostroun Katherine , Go Virginia-Arlene , Robinson Randal D.
Published: June 2023

Purpose of review

Nontubal ectopic pregnancies appear to be increasing in prevalence. Increasingly, minimally invasive methods for management are being utilized. A current literature review and recommendations for management of nontubal ectopic pregnancy is presented in this review.

Recent findings

Nontubal ectopic pregnancies are less common than tubal ectopic pregnancies but present a unique and significant threat to patient's health and are optimally managed by specialists familiar with the condition. Early diagnosis, prompt treatment and close follow-up to resolution are critical. Recent publications focus on fertility-sparing and conservative management through the use of medications both systemic and local; as well as minimally invasive surgical techniques. The Society of Maternal Fetal Medicine recommends against expectant management of cesarean scar pregnancies; however, optimal treatment is unknown and this holds true for management of other nontubal ectopic pregnancies.

Minimally invasive and fertility sparing management should be the mainstay in treatment of stable patients with nontubal ectopic pregnancy.
Skeletal muscle relaxants for the treatment of myofascial pelvic pain and high tone pelvic floor disorders
Authors: Flatow Virginia , Uy-Kroh Jean , Carey Erin T. , Ascher-Walsh Charles , Khalil Susan
Published: June 2023

Purpose of review

Chronic pelvic main is a complex process that includes many causes. In gynecology, the treatment of myofascial pelvic pain and high tone pelvic floor disorders can be managed with skeletal muscle relaxants for select clinical indications. A review of skeletal muscle relaxants will be included for gynecologic indications.

Recent findings

There are limited studies on vaginal skeletal muscle relaxants, but there can be oral forms used for chronic myofascial pelvic pain. They function as antispastic, antispasmodic, and combination of the two modes of action. Diazepam is the most studied for myofascial pelvic pain in both oral and vaginal formulations. Its use can be combined with multimodal management to optimize outcomes. Other medications have limitations due to dependency and limited studies that demonstrate improvement in pain scales.

Skeletal muscle relaxants have limited high quality studies for chronic myofascial pelvic pain. Their use can be combined with multimodal options to improve clinical outcomes. Additional studies are needed for vaginal preparations and evaluation of safety and clinical efficacy for patient reported outcomes measures in patients living with chronic myofascial pelvic pain.
Detection Capability of 89Sr and 90Sr Using Liquid Scintillation Counting
Authors: Blain Ezekiel , Nishikawa Kimi , Faye Sherry A. , Roselan Amy , Burn Adam G. , Torres Miguel A. , Semkow Thomas M.
Published: June 2023

We developed a new method for simultaneous determination of 89Sr and 90Sr with an emphasis on detectability. The samples were digested, and Sr was chemically purified followed by a single count on a liquid scintillation counter in three windows overlapping the 90Sr, 89Sr, and 90Y peaks. Gamma spectrometry was used to measure 85Sr, added for chemical recovery. The method was tested on 18 water samples spiked at levels from 9 to 242 Bq of 89Sr and 90Sr, with either single radionuclides or their mixtures. In addition, eight method blanks were measured. The data were analyzed numerically by solving a system of linear equations for 89Sr and 90Sr activities as analytes and 90Y activity as a participating component. The total uncertainties of the results were calculated numerically using variances and covariances. The average bias from the known activities was −0.3% (range from −3.6 to 3.1%) for 90Sr and − 1.5% (range from −10.1 to 5.1%) for 89Sr. The En
-scores were within −1.0 and 1.0 at 95% confidence level. The detection capabilities of this method were determined by means of the decision threshold LC
and the limit of detection referred to as the minimum detectable activity. All relevant uncertainties were propagated into the LC
and minimum detectable activity. In addition, detection limits were calculated for the purpose of Safe Drinking Water Act monitoring. The detection capabilities were compared with the regulatory requirements in the US and EU for food and water. For samples spiked with either pure 89Sr or 90Sr, false positives were observed for the opposite radionuclide exceeding the above LC
values. This was attributed to interference by the spiked activity. A new method was developed to calculate decision and detectability curves in the presence of interference.
Understanding the Health and Well-being of Women With Multiple Sclerosis
Authors: Collins Jennifer , Babenko-Mould Yolanda , Jackson Kimberley T. , Smith-Carrier Tracy
Published: June 2023

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system, and is potentially disabling. Women experience MS more frequently than men at a 3:1 ratio. Current literature suggests that women may experience health, social determinants of health, and disability differentially, and there is a gap in the research examining how gender intersects with MS. METHODS: Interviews were conducted with 23 women with MS. van Manen's hermeneutic phenomenology was used to inform and analyze the data to understand the nature and meaning of health and well-being for participants. RESULTS: A key theme of “enhancing wholeness for women with MS” emerged from the data, which suggests that women with MS view themselves as healthy and “whole” despite living with MS. Supporting factors for physical, mental, and social well-being include the ability to enact human agency within social structures such as with employment or seeking care with MS clinics. The findings informed the development of a figure that depicts the supporting factors of health and well-being for women living with MS. CONCLUSION: The health and well-being of women with MS may be optimally supported by nurses and interdisciplinary healthcare teams through careful consideration as to how agency is enacted within social structures, for example, MS clinics, employment, and social support systems, as well as considerations for social determinants of health.
Shoulder Check: Investigating Shoulder Injury Rates, Types, Severity, Mechanisms, and Risk Factors in Canadian Youth Ice Hockey
Authors: Gibson Eric S. , Eliason Paul H. , West Stephen W. , Black Amanda M. , Lebrun Constance , Emery Carolyn A. , Pasanen Kati
Published: June 2023

Objective:

To describe shoulder-related injury rates (IRs), types, severity, mechanisms, and risk factors in youth ice hockey players during games and practices.

Design:

Secondary analysis of data from a 5-year prospective cohort study, Safe-to-Play (2013-2018).

Setting:

Canadian youth ice hockey.

Participants:

Overall, 6584 player-seasons (representing 4417 individual players) participated. During this period, 118 shoulder-related games and 12 practice injuries were reported.

Assessment of Risk Factors:

An exploratory multivariable mixed-effects Poisson regression model examined the risk factors of body checking policy, weight, biological sex, history of injury in the past 12 months, and level of play.

Main Outcome Measures:

Injury surveillance data were collected from 2013 to 2018. Injury rates with 95% confidence interval (CI) were estimated using Poisson regression.

Results:

The shoulder IR was 0.35 injuries/1000 game-hours (95% CI, 0.24-0.49). Two-thirds of game injuries (n = 80, 70%) resulted in >8 days of time-loss, and more than one-third (n = 44, 39%) resulted in >28 days of time-loss. An 83% lower rate of shoulder injury was associated with policy prohibiting body checking compared with leagues allowing body checking (incidence rate ratio [IRR], 0.17; 95% CI, 0.09-0.33). A higher shoulder IR was observed for those who reported any injury in the last 12-months compared with those with no history (IRR, 2.00; 95% CI, 1.33-3.01).

Conclusions:

Most shoulder injuries resulted in more than 1 week of time-loss. Risk factors for shoulder injury included participation in a body-checking league and recent history of injury. Further study of prevention strategies specific to the shoulder may merit further consideration in ice hockey.
Findings From the 2021 Organizational Value of Nursing Professional Development Practice, Part 3
Authors: Harper Mary G. , MacDonald Ryan , Maloney Patsy , Aucoin Julia
Published: June 2023

In 2021, the Association for Nursing Professional Development commissioned a national study to examine relationships between nursing professional development (NPD) staffing and organizational outcomes and to compare NPD staffing in pediatric and adult hospitals. This report compares data from children's and adult hospitals, which indicate that children's hospitals, in general, have significantly more staffing resources, including NPD practitioners. Insufficient data were obtained to examine relationships between NPD staffing in children's hospitals and organizational outcomes.
De-escalation Techniques for the Agitated Pediatric Patient
Authors: Georgadarellis Alexandria G. , Baum Carl R.
Published: June 2023

The emergency department can be a particularly challenging environment for the care of pediatric patients presenting with acute agitation. Agitation is a behavioral emergency requiring prompt intervention. Timely recognition of agitation and proactive implementation of de-escalation strategies are critical for safe and effective management of agitation, as well as prevention of recurrent episodes. This article reviews the definition of agitation, explores the domains of verbal de-escalation, and considers multidisciplinary management strategies for children with acute agitation.
Intraoperative Indocyanine Green Angiography Facilitates Flap Fenestration and Facial Organ Fabrication in Total Facial Restoration
Authors: Huang Xin , Li Haizhou , Gu Shuchen , Gao Yashan , Khoong Yimin , Liu Yunhan , Luo Shenying , Gu Bin , Li Qingfeng , Zan Tao
Published: June 2023

Background:

Because of a lack of effective measures to visualize flap vasculature and perfusion, flap fenestration and facial organ fabrication cannot be performed effectively, preventing the transition from two-dimensional coverage to restoration of the three-dimensional (3D) structure of facial organs. This study aimed to evaluate the efficacy of indocyanine green angiography (ICGA) in guiding flap fenestration and facial organ fabrication in total facial restoration.

Methods:

Ten patients with total facial scarring after burn injury were enrolled in the study. They were treated with preexpanded, prefabricated monoblock flaps for total face restoration. The openings of nostrils and oral and palpebral orifices, together with organ fabrication, were conducted under the guidance of intraoperative ICGA by hemodynamic evaluation of flap perfusion. Postoperative follow-up measures include vascular crisis, infection, flap necrosis, and aesthetic and functional recovery.

Results:

The opening of facial organ orifices was performed at the stage of flap transfer in nine patients. To avoid damaging the major nourishing vessels, the left palpebral orifice was opened 8 days after the flap transfer in one patient, as observed by ICGA. Based on ICGA evaluation, the decision to perform additional vascular anastomosis before flap fenestration was made in six patients. Hemodynamic analysis of flap perfusion after fenestration revealed no significant change. Follow-up showed satisfactory aesthetic recovery and well-restored 3D structures of facial organs.

Conclusion:

This pilot study demonstrates how intraoperative ICGA can enhance the safety of flap fenestration, thereby transforming full facial restoration from the two-dimensional to the 3D realm by facilitating facial organ fabrication.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Physical activity is associated with adiposity in older adults with HIV in the modern HIV era
Authors: Webel Allison R. , Davey Christine Horvat , Oliveira Vitor , Cleveland Dave , Crane Heidi M. , Gripshover Barbara M. , Long Dustin M. , Fleming Julia G. , Buford Thomas W. , Willig Amanda L.
Published: June 2023

Objectives:

People with HIV (PWH) are aging and are experiencing higher rates of abdominal adiposity. Physical activity is an effective nonpharmacological strategy to reduce adiposity in the general aging population. Yet, the relationship between physical activity and adiposity in people with well controlled HIV is unclear. Our objective was to describe the association between objectively-measured physical activity and abdominal adiposity in PWH.

Methods:

As part of the multisite, observational PROSPER-HIV study, virologically suppressed, adult PWH wore an Actigraph accelerometer for 7–10 days and completed duplicate waist and hip circumference measures. Demographic and medical characteristics were abstracted from the CFAR Network of Integrated Clinical Systems dataset. Descriptive statistics and multiple linear regressions were used to analyze the data.

Results:

On average, our 419 PWH were 58 years of age [interquartile range (IQR): 50, 64], male (77%), Black (54%), and currently taking an integrase inhibitor (78%). PWH completed a mean of 7.06 (±2.74) days of total actigraphy wear time. They took an average of 4905 (3233, 7140) steps per day and engaged in 5.4 h of sedentary time per day. Controlling for age, sex, employment and integrase inhibitor use, the number of steps taken per day was associated with reduced abdominal adiposity (F = 3.27;P < 0.001) and the hours of daily sedentary time was associated with increased abdominal adiposity (F = 3.24;P < 0.001).

Conclusions:

Greater physical activity is associated with reduced abdominal adiposity in aging PWH. Future work should investigate how to tailor the amount, type and intensity of physical activity needed to reduce adiposity in PWH taking contemporary HIV medication.

Registration number:

NCT03790501.
Association of CD4 count and HIV viral load with risk of Non-AIDS-defining cancers
Authors: MA Yunqing , Zhang Jiajia , Yang Xueying , Chen Shujie , Weissman Sharon , Olatosi Bankole , Alberg Anthony , Li Xiaoming
Published: June 2023

Objectives:

HIV-induced immunodeficiency contributes to an increased risk of non-AIDS-defining cancers (NADC). This study aims to identify the most predictive viral load (VL) or CD4 measures of NADC risk among people living with HIV (PLWH).

Design:

Extracted from South Carolina electronic HIV reporting system, we studied adult PLWH who were cancer-free at baseline and had at least 6 months of follow-up since HIV diagnosis between January 2005 and December 2020.

Methods:

Using multiple proportional hazards models, risk of NADC was investigated in relation to twelve measures of VL and CD4 at three different time intervals before NADC diagnosis. The best VL/CD4 predictor(s) and final model were determined using Akaike's information criterion.

Results:

Among 10,413 eligible PLWH, 449 (4.31%) developed at least one type of NADC. After adjusting for potential confounders, the best predictors of NADC were the proportion of days with viral suppression (hazard ratio [HR]: 0.47 (>25% and ≤50% vs =0), 95% confidence interval [CI]: [0.28, 0.79]) and proportion of days with low CD4 count (AIC = 7201.35) (HR: 12.28 (>75% vs = 0), 95% CI: [9.29, 16.23]).

Conclusions:

VL and CD4 measures are strongly associated with risk of NADC. In analyses examining three time windows, proportion of days with low CD4 count was the best CD4 predictor for each time window. However, the best VL predictor varied across time windows. Thus, using the best combination of VL and CD4 measures for a specific time window should be considered when predicting NADC risk.
Postdoctoral National Institutes of Health F32 Grants
Authors: Narahari Adishesh K. , Chandrabhatla Anirudha S. , Fronk Emily , White Simon , Mandava Shreya , Jacobs-El Hannah , Mehaffey J. Hunter , Tribble Curtis G. , Roeser Mark , Kern John , Kron Irving L. , Schirmer Bruce
Published: June 2023

Objective:

We examined trainees in surgery and internal medicine who received National Institutes of Health (NIH) F32 postdoctoral awards to determine their success rates in obtaining future NIH funding.

Summary Background Data:

Trainees participate in dedicated research years during residency (surgery) and fellowship (internal medicine). They can obtain an NIH F32 grant to fund their research time and have structured mentorship.

Methods:

We collected NIH F32 grants (1992-2021) for Surgery Departments and Internal Medicine Departments from NIH RePORTER, an online database of NIH grants. Non-surgeons and non-internal medicine physicians were excluded. We collected demographic information on each recipient including gender, current specialty, leadership positions, graduate degrees, and any future NIH grants they received. A Mann-Whitney U test was used for continuous variables and a χ2 test was utilized to analyze categorical variables. An alpha value of 0.05 was used to determine significance.

Results:

We identified 269 surgeons and 735 internal medicine trainees who received F32 grants. A total of 48 surgeons (17.8%) and 339 internal medicine trainees (50.2%) received future NIH funding (P < 0.0001). Similarly, 24 surgeons (8.9%) and 145 internal medicine trainees (19.7%) received an R01 in the future (P < 0.0001). Surgeons who received F32 grants were more likely to be department chair or division chief (P =0.0055 and P < 0.0001).

Conclusions:

Surgery trainees who obtain NIH F32 grants during dedicated research years are less likely to receive any form of NIH funding in the future compared to their internal medicine colleagues who received F32 grants.
Recurrence after Surgery for Primary Hyperparathyroidism in 517 Patients with Multiple Endocrine Neoplasia Type 1. An AFCE and GTE study (Association Francophone de Chirurgie Endocrinienne and Groupe d’étude des Tumeurs Endocrines)
Authors: Santucci Nicolas , Ksiazek Elea , Pattou François , Baud Gregory , Mirallié Eric , Frey Samuel , Trésallet Christophe , Sébag Frédéric , Guérin Carole , Mathonnet Muriel , Christou Niki , Donatini Gianluca , Brunaud Laurent , Gaujoux Sébastien , Ménégaux Fabrice , Najah Haythem , Binquet Christine , Goudet Pierre , Lifante Jean-Christophe
Published: June 2023

Objective:

To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in MEN1 patients and to identify the risk factors for recurrence after initial surgery.

Summary Background Data:

In MEN 1 patients, pHPT is multiglandular and the optimal extent of initial parathyroid resection influences the risk of recurrence.

Methods:

MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal (LTSP) and subtotal (STP) were analyzed. Patients with total parathyroidectomy (TP) with reimplantation were excluded.

Results:

517 patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher following LTSP (68.5%) than STP (45%) (P<0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years (P<0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (Odds Ratio=2.19; 95% CI [1.31; 3.69] P=0.003). The five and ten-year recurrent pHPT probabilities were significantly higher in patients after LTSP with mutation in exon 10 (37% and 79% versus 30% and 61% P=0.016).

Conclusion:

Persistence, recurrence of pHPT and reoperation rate are significantly lower after STP than LTSP in MEN 1 patients. Genotype seems to be associated with recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP and LTSP may not be recommended when exon 10 is mutated.
Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers
Authors: Gibson Lucy L. , Abdelnour Carla , Chong Joyce , Ballard Clive , Aarsland Dag
Published: June 2023

Purpose of review

Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges.

Recent findings

Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future.

In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.
Evaluation of volumetric asymmetry of the dorsolateral prefrontal cortex and medial temporal lobe in Alzheimer’s disease using the atlas-based method
Authors: Karaca Omur , Tepe Nermin , Ozcan Emrah
Published: June 2023

Brain areas affected during neurodegenerative disease progression are considered anatomically connected to the first affected areas. The dorsolateral prefrontal cortex (DLPFC) has connections with the medial temporal lobe (MTL), which includes regions that become atrophic in Alzheimer’s disease. In this study, we aimed to investigate the degree of volumetric asymmetry of DLPFC and MTL structures. This is a cross-sectional volumetric study involving 25 Alzheimer’s disease patients and 25 healthy adults who underwent MRI with a 3D turbo spin echo sequence at 1.5 Tesla. The atlas-based method incorporated MRIStudio software to automatically measure the volume of brain structures. We compared the asymmetry index and volumetric changes across study groups and correlated them with Mini-Mental State Examination scores. We observed significant volumetric rightward lateralization in the DLPFC and superior frontal gyrus in Alzheimer’s disease patients compared to the healthy controls. There was a significant volume loss in the MTL structures of Alzheimer’s disease patients. Atrophy of MTL structures was positively correlated with right DLPFC volume changes in Alzheimer’s disease patients. Volumetric asymmetry of the DLPFC may be a characteristic for determining disease progression in Alzheimer’s disease patients. Future studies are recommended to evaluate whether these volumetric asymmetrical changes are specific to Alzheimer’s disease and whether asymmetry measurements can serve as diagnostic markers.
A Transdiagnostic Structural Brain Signature of Parkinsonian and Essential Tremor
Authors: Ineichen Christian , Callaghan Fraser , Baumann-Vogel Heide , Büchele Fabian , O’Gorman Tuura Ruth , Baumann Christian R. , Schreiner Simon J.
Published: June 2023

Background

Parkinson’s disease (PD) and Essential Tremor (ET) are heterogeneous, yet distinct disorders. At the same time, PD and ET show overlapping features such as phenotypes with predominant tremor. These heterogeneities and overlaps pose challenges for clinical management and research and may indicate transdiagnostic, shared mechanisms for tremor.

Objectives

To test the hypothesis that MRI may reveal structural brain changes related to tremor phenotypes rather than diagnoses in PD and ET patients. For this, we compared regional brain volumes between three patient groups with overlapping phenotypes and distinct diagnoses: ET, PD with tremor-dominant phenotype (PD-T), and PD with non-tremor-dominant phenotype (PD-nT).

Methods

We studied 164 patients (18 ET, 38 PD-T, 108 PD-nT) who were evaluated for deep brain stimulation. All patients underwent structural MRI, and standardized assessment of motor symptoms. We compared regional brain volumes between groups.

Results

Volumes of the thalamus, pallidum, and pre-cerebellar and upper brainstem (midbrain, pons, superior cerebellar peduncle) differed across groups and were smallest in ET, intermediate in PD-T, and largest in PD-nT. Differences reached significance when comparing ET or PD-T with PD-nT but not ET with PD-T. Thalamic and brainstem volumes correlated with more severe and less levodopa-responsive tremor in PD. In contrast to the subcortical findings, cortical thickness in frontal and parietal regions was thinner in PD-nT compared to PD-T patients.

Conclusions

We identified tremor-related volume loss in cerebellothalamic and interconnected regions (pallidum), potentially suggesting shared mechanisms of tremor in PD and ET and pointing towards a transdiagnostic structural brain signature of tremor.
Single-cell multiplex chromatin and RNA interactions in aging human brain
Authors: Wen Xingzhao , Luo Zhifei , Zhao Wenxin , Calandrelli Riccardo , Nguyen Tri C. , Wan Xueyi , Richard John Lalith Charles , Zhong Sheng
Published: June 2023

SUMMARY PARAGRAPH

The dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA (caRNA)1–3. Chromatin complex compositions change during cellular differentiation and aging, and are expected to be highly heterogeneous among terminally differentiated single cells4–7. Here we introduce theMulti-Nucleic Acid Interaction Mapping inSingleCell (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within individual nuclei. Applied to 14 human frontal cortex samples from elderly donors, MUSIC delineates diverse cortical cell types and states. We observed the nuclei exhibiting fewer short-range chromatin interactions are correlated with an “older” transcriptomic signature and with Alzheimer’s pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci (cis eQTLs) and a promoter tends to be the cell type where these cis eQTLs specifically affect their target gene’s expression. Additionally, the female cortical cells exhibit highly heterogeneous interactions between the XIST non-coding RNA and Chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploring chromatin architecture and transcription at cellular resolution in complex tissues.
The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation
Authors: Xu Hang , Yuan Zihao , Qin Kunpeng , Jiang Shuai , Sun Li
Published: June 2023

Caspase (CASP) is a family of proteases involved in cleavage and activation of gasdermin, the executor of pyroptosis. In human, CASP3 and CASP7 recognize the same consensus motif DxxD, which is present in gasdermin E (GSDME). However, human GSDME is cleaved by CASP3 but not by CASP7. The underlying mechanism of this observation is unclear. In this study, we identified a pyroptotic pufferfish GSDME that was cleaved by both pufferfish CASP3/7 and human CASP3/7. Domain swapping between pufferfish and human CASP and GSDME showed that the GSDME C-terminus and the CASP7 p10 subunit determined the cleavability of GSDME by CASP7. p10 contains a key residue that governs CASP7 substrate discrimination. This key residue is highly conserved in vertebrate CASP3 and in most vertebrate (except mammalian) CASP7. In mammals, the key residue is conserved in non-primate (e.g., mouse) but not in primate. However, mouse CASP7 cleaved human GSDME but not mouse GSDME. These findings revealed the molecular mechanism of CASP7 substrate discrimination and the divergence of CASP3/7-mediated GSDME activation in vertebrate. These results also suggested that mutation-mediated functional alteration of CASP probably enabled the divergence and specialization of different CASP members in the regulation of complex cellular activities in mammals.
Vibrio choleraeArrests Intestinal Epithelial Proliferation through T6SS-dependent Activation of the Bone Morphogenetic Protein Pathway
Authors: Xu Xinyue , Foley Edan
Published: June 2023

To maintain an effective barrier, intestinal epithelial progenitor cells must divide at a rate that matches the loss of dead and dying cells. Otherwise, epithelial breaches expose the host to systemic infection by gut-resident microbes. Unlike most pathogens,Vibrio choleraeblocks tissue repair by arresting progenitor proliferation in theDrosophilainfection model. At present, we do not understand howVibriocircumvents such a critical antibacterial defense. In a series of genetic experiments, we found thatV. choleraeblocks epithelial repair by activating the growth inhibitor Bone Morphogenetic Protein (BMP) pathway in progenitors. Specifically, we discovered that interactions betweenVibrioand gut commensals initiate BMP signaling via host innate immune defenses. Notably, we found thatVibrioalso activates BMP and arrests proliferation in zebrafish intestines, indicating an evolutionarily conserved link between infection, BMP and failure in tissue repair. Combined, our study highlights how enteric pathogens engage host immune and growth regulatory pathways to disrupt intestinal epithelial repair.
Chemically induced partial unfolding of the multifunctional Apurinic/apyrimidinic endonuclease 1
Authors: Rai Ratan , Dawodu Olabode I. , Johnson Steven M. , Vilseck Jonah Z. , Kelley Mark R. , Ziarek Joshua J. , Georgiadis Millie M.
Published: June 2023

Targeting of the multifunctional enzyme apurinic/apyrimidinic endonuclease I/redox factor 1 (APE1) has produced small molecule inhibitors of both its endonuclease and redox activities. While one of the small molecules, the redox inhibitor APX3330, completed a Phase I clinical trial for solid tumors and a Phase II clinical trial for Diabetic Retinopathy/Diabetic Macular Edema, the mechanism of action for this drug has yet to be fully understood. Here, we demonstrate through HSQC NMR studies that APX3330 induces chemical shift perturbations (CSPs) of both surface and internal residues in a concentration-dependent manner, with a cluster of surface residues defining a small pocket on the opposite face from the endonuclease active site of APE1. Furthermore, APX3330 induces partial unfolding of APE1 as evidenced by a time-dependent loss of chemical shifts for approximately 35% of the residues within APE1 in the HSQC NMR spectrum. Notably, regions that are partially unfolded include adjacent strands within one of two beta sheets that comprise the core of APE1. One of the strands comprises residues near the N-terminal region and a second strand is contributed by the C-terminal region of APE1, which serves as a mitochondrial targeting sequence. These terminal regions converge within the pocket defined by the CSPs. In the presence of a duplex DNA substrate mimic, removal of excess APX3330 resulted in refolding of APE1. Our results are consistent with a reversible mechanism of partial unfolding of APE1 induced by the small molecule inhibitor, APX3330, defining a novel mechanism of inhibition.
As predicted and more: modulated channel occupation in YZn5+x
Authors: Fredrickson Rie T. , Fredrickson Daniel C.
Published: June 2023

Like many complex intermetallic phases, the crystal structures of REZn5+xcompounds (RE = lanthanide or Group 3 element) based on the EuMg5type have gradually unfolded. The original reports described a complex hexagonal structure with an unusual combination of tetrahedrally close-packed regions and open spaces, as well as observations of superstructure reflections. More recently, we reinvestigated the structure of YZn5, reclassifying it as the EuMg5+x-type compound YZn5+x(x ≃ 0.2), in which disordered channels run alongcthrough the spaces formerly considered open. In addition, DFT-chemical pressure (DFT-CP) analysis of ordered models of YZn5+xhighlighted paths for communication between neighboring channels setting the stage for superstructure formation. Herein, the experimental elucidation of this effect is presented with the synthesis and structure determination of a modulated form of YZn5+x. By slow-cooling samples of YZn5+xfrom the annealing temperature, crystals were obtained that exhibit satellite reflections with the modulation wavevectorq= {1\over 3}a*+ {1\over 3}b*+ 0.3041c*. Structure solution and refinement using a (3+1)D model in superspace groupP31c({1\over 3}\,\!{1\over 3}σ3)00sreveals incommensurate order in the structure's channels. Here, two Zn sites associated with the channels are present, each with discontinuous atomic domains that are slanted in thex3x4plane. Their slanting corresponds to adjustments along thecaxis for the presence or absence of close neighbors along that axis, while the occupation patterns of neighboring channels are shifted by {1\over 3} of the modulation period. These features follow earlier predictions from CP analysis, highlighting how this approach can be used predictively in search of new phenomena.
Module walking using an SH3-like cell-wall-binding domain leads to a new GH184 family of muramidases
Authors: Moroz Olga V. , Blagova Elena , Lebedev Andrey A. , Skov Lars K. , Pache Roland A. , Schnorr Kirk M. , Kiemer Lars , Friis Esben P. , Nymand-Grarup Søren , Ming Li , Ye Liu , Klausen Mikkel , Cohn Marianne T. , Schmidt Esben G. W. , Davies Gideon J. , Wilson Keith S.
Published: June 2023

Muramidases (also known as lysozymes) hydrolyse the peptidoglycan component of the bacterial cell wall and are found in many glycoside hydrolase (GH) families. Similar to other glycoside hydrolases, muramidases sometimes have noncatalytic domains that facilitate their interaction with the substrate. Here, the identification, characterization and X-ray structure of a novel fungal GH24 muramidase from Trichophaea saccata is first described, in which an SH3-like cell-wall-binding domain (CWBD) was identified by structure comparison in addition to its catalytic domain. Further, a complex between a triglycine peptide and the CWBD from T. saccata is presented that shows a possible anchor point of the peptidoglycan on the CWBD. A `domain-walking' approach, searching for other sequences with a domain of unknown function appended to the CWBD, was then used to identify a group of fungal muramidases that also contain homologous SH3-like cell-wall-binding modules, the catalytic domains of which define a new GH family. The properties of some representative members of this family are described as well as X-ray structures of the independent catalytic and SH3-like domains of the Kionochaeta sp., Thermothielavioides terrestris and Penicillium virgatum enzymes. This work confirms the power of the module-walking approach, extends the library of known GH families and adds a new noncatalytic module to the muramidase arsenal.
Impact of virtual reality immersion on customer experience: moderating effect of cross-sensory compensation and social interaction
Authors: Mou Yupeng , Fan Jiao , Ding Zhihua , Khan Inayat
Published: June 2023

Purpose

In order to encourage customers to try experience virtual tourism, researchers and practitioners pay more attention on how to improve customers' perception of authenticity.

Design/methodology/approach

Using the theory of cross-sensory compensation, through 4 experiments, this study examines the impact of social interaction and cross-sensory strategies on the relationship between virtual reality (VR) and improving customers' perception of authenticity and customer experience.

Findings

Through experimental research, this paper finds that (1) VR immersion has a significant positive impact on perception of authenticity, which in turn acts on customers' virtual tourism experience. (2) In addition, social interaction strengthens the relationship between VR immersion and customers' perception of authenticity. (3) The cross-sensory compensation has a positive effect on VR immersion to enhance customers' perception of authenticity.

Originality/value

The research conclusion provides a direction for further discussion on how to improve customers' perception of authenticity and provides theoretical guidance and reference for the virtual tourism industry.