bluuebunny/crossref_metadata_2025_split huggingface dataset:
Terminology and Guidelines for Diagnostic Assay Development and Validation: Best Practices for Molecular Tests
Authors: Groth-Helms Deborah , Rivera Yazmín , Martin Frank N. , Arif Mohammad , Sharma Poonam , Castlebury Lisa A. 
Published: May 2023

Effective use of diagnostic assays is essential for the early detection of plant pathogens and mitigation of potential disease impacts. Assay developers require a full understanding of the intended use of a test to address complicating factors that might be observed by an end user and limit the utility of the test and its scope of application in the field. The fitness of a test for a disease prevention application is determined by its performance characteristics, which are selected during assay design and defined during validation. This paper provides guidance to developers by standardizing the descriptions of key validation terms and concepts, including tiers that can be referenced in publications to better communicate the extent to which a test has been validated. These concepts are then applied in the broader context of a strategic approach to validation for various taxa and methods. The aim of this paper is to increase awareness of common pitfalls and gaps encountered during this process, with the goal of increased success in technology transfer. Recommendations are given for improving the efficiency and quality of test development through improved coordination among stakeholders. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Estrogen deficiency accelerates postmenopausal atherosclerosis by inducing endothelial cell ferroptosis through inhibiting NRF2/GPX4 pathway
Authors: Lv Ying , Zhang Shan , Weng Xiuzhu , Huang Jianxin , Zhao Honggang , Dai Xinyu , Bai Xiaoxuan , Bao Xiaoyi , Zhao Chen , Zeng Ming , Bai Yunshu , Hu Sining , Li Ji , Jia Haibo , Yu Bo 
Published: May 2023

AbstractOxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE−/− mice fed with high‐fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin‐1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized‐low‐density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti‐ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.
Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain
Authors: de Zoete Rutger M. J. , Berryman Carolyn F. , Nijs Jo , Walls Angela , Jenkinson Mark 
Published: May 2023

Objectives:
Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention. The primary aim was to investigate changes in structural brain characteristics after physical exercise therapy for people with chronic nonspecific neck pain. The secondary aims were to investigate (1) baseline differences in structural brain characteristics between responders and nonresponders to exercise therapy, and (2) differential brain changes after exercise therapy between responders and nonresponders.

Materials and Methods:
This was a prospective longitudinal cohort study. Twenty-four participants (18 females, mean age 39.7 y) with chronic nonspecific neck pain were included. Responders were selected as those with ≥20% improvement in Neck Disability Index. Structural magnetic resonance imaging was obtained before and after an 8-week physical exercise intervention delivered by a physiotherapist. Freesurfer cluster-wise analyses were performed and supplemented with an analysis of pain-specific brain regions of interest.

Results:
Various changes in grey matter volume and thickness were found after the intervention, for example, frontal cortex volume decreased (cluster-weighted P value = 0.0002, 95% CI: 0.0000-0.0004). We found numerous differences between responders and nonresponders, most notably, after the exercise intervention bilateral insular volume decreased in responders, but increased in nonresponders (cluster-weighted P value ≤ 0.0002).

Discussion:
The brain changes found in this study may underpin clinically observed differential effects between responders and nonresponders to exercise therapy for people with chronic neck pain. Identification of these changes is an important step toward personalized treatment approaches.
Biologically Interpretable Deep Learning To Predict Response to Immunotherapy In Advanced Melanoma Using Mutations and Copy Number Variations
Authors: Zhang Liuchao , Cao Lei , Li Shuang , Wang Liuying , Song Yongzhen , Huang Yue , Xu Zhenyi , He Jia , Wang Meng , Li Kang 
Published: May 2023

Only 30–40% of advanced melanoma patients respond effectively to immunotherapy in clinical practice, so it is necessary to accurately identify the response of patients to immunotherapy pre-clinically. Here, we develop KP-NET, a deep learning model that is sparse on KEGG pathways, and combine it with transfer- learning to accurately predict the response of advanced melanomas to immunotherapy using KEGG pathway-level information enriched from gene mutation and copy number variation data. The KP-NET demonstrates best performance with AUROC of 0.886 on testing set and 0.803 on an unseen evaluation set when predicting responders (CR/PR/SD with PFS ≥6 mo) versus non-responders (PD/SD with PFS <6 mo) in anti-CTLA-4 treated melanoma patients. The model also achieves an AUROC of 0.917 and 0.833 in predicting CR/PR versus PD, respectively. Meanwhile, the AUROC is 0.913 when predicting responders versus non-responders in anti-PD-1/PD-L1 melanomas. Moreover, the KP-NET reveals some genes and pathways associated with response to anti-CTLA-4 treatment, such as genes PIK3CA, AOX1 and CBLB, and ErbB signaling pathway, T cell receptor signaling pathway, et al. In conclusion, the KP-NET can accurately predict the response of melanomas to immunotherapy and screen related biomarkers pre-clinically, which can contribute to precision medicine of melanoma.
Greater Number of Plasma Exchanges Does Not Improve Outcome in Myasthenic Crisis
Authors: Hansen Michael , Neilson Lee , Parikh Melanie , Katirji Bashar 
Published: May 2023

Abstract

Objectives:
To determine the relationship between the number of plasma exchanges and clinical outcome in patients experiencing myasthenic crisis.

Methods:
We retrospectively reviewed all episodes of myasthenia gravis exacerbation/crisis who received plasmapheresis in patients admitted to a single-center tertiary care referral center from July 2008 to July 2017. We performed statistical analyses to determine whether the increased number of plasma exchanges improves the primary outcome (hospital length of stay) and the secondary outcome (disposition to home, skilled nursing facility, long-term acute care hospital, or death).

Results:
There is neither clinically observable nor statistically significant improvement in length of stay or disposition on discharge in patients who received 6 or greater sessions of plasmapheresis.

Conclusions:
This study provides class IV evidence that extending the number of plasma exchanges beyond 5 does not correlate with decreased hospital length of stay or improved discharge disposition in patients experiencing myasthenic crisis.
Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis
Authors: Li Xiaoyan , Koeberl Dwight D. , Lutz Michael W. , Bedlack Richard 
Published: May 2023

Abstract

Objective:
Clenbuterol, a beta-agonist, has plausible mechanisms for treating amyotrophic lateral sclerosis (ALS). In this highly inclusive open-label trial (NCT04245709), we aimed to study the safety and efficacy of clenbuterol in patients with ALS.

Methods:
All participants received clenbuterol starting at 40 μg daily and increased to 80 μg twice daily. Outcomes included safety, tolerability, ALS Functional Rating Score (ALSFRS-R) progression, forced vital capacity (FVC) progression, and myometry. ALSFRS-R and FVC slopes measured during treatment were compared with slopes before treatment (calculated by assuming ALSFRS-R was 48 and FVC was 100% at ALS onset).

Results:
The 25 participants had a mean age of 59, mean disease duration of 43 months, ALSFRS-R score at enrollment 34, and FVC at enrollment 77%. Forty-eight percent were female, 68% were taking riluzole, and none were taking edaravone. Two participants experienced severe adverse events, neither related to the study. Twenty-four participants experienced adverse events, most commonly tremors/jitters, cramps/spasms, insomnia, and stiffness/spasticity. Fourteen participants withdrew early from the trial, 13 due to adverse events. Patients who withdrew early were significantly older and more likely to be male. Per-protocol and intention-to-treat analyses showed meaningfully slower ALSFRS-R and FVC progression during treatment. Hand grip dynamometry and myometry changes were highly variable between participants; most declined slowly, but some showed improvements.

Conclusions:
Clenbuterol was safe but less tolerable at the doses we selected compared with an earlier Italian case series. Consistent with that series, our study suggested benefits on ALS progression. However, the latter result should be interpreted with caution as our study is limited by small sample size, large drop out, lack of randomization, and blinding and placebo controls. A larger, more traditional trial now seems warranted.
Frequency and Magnitude of Obstacles and Helpful Behavior Items in End-of-Life Care as Perceived by Nurses Working in Critical-Access Hospitals
Authors: Beckstrand Renea L. , Larsen Shalyn , Macintosh Janelle L. B. , Rasmussen Ryan , Luthy Karlen E. , Lyman Trissa M. 
Published: May 2023

Background
Twenty percent of Americans live in rural areas where most of their health care is provided in critical-access hospitals (CAHs). It is unknown how frequently obstacle and helpful behavior items occur in end-of-life (EOL) care in CAHs.

Objectives
The aims of this study were to determine the frequency of occurrence scores of obstacle and helpful behavior items in providing EOL care in CAHs and to also determine which obstacles and helpful behaviors have the greatest or least impact on EOL care based on the magnitude scores.

Methods
A questionnaire was sent to nurses working in 39 CAHs in the United States. Nurse participants were asked to rate obstacle and helpful behavior items by size and frequency of occurrence. Data were analyzed to quantify the impact of obstacle and helpful behavior items on EOL care in CAHs by multiplying the mean size by the mean frequency of items to determine mean magnitude scores.

Results
Items with the highest and lowest frequency were determined. In addition, obstacle and helpful behavior item magnitude scores were calculated. Seven of the top 10 obstacles were related to patients' families. Seven of the top 10 helpful behaviors involved nurses ensuring families had positive experiences.

Conclusion
Nurses in CAHs perceived issues around patient family members as significant obstacles to EOL care. Nurses work to ensure that families have positive experiences. Visiting hour issues seemed to be irrelevant. The use of technology, such as telehealth, seemed to provide little benefit in EOL care in CAHs.
Evaluation of Training in Identifying and Responding to Suicide Risk by Staff of a Behavioral Health Managed Care Organization
Authors: Walker Marcie L. , Weems Lori A. , Hutchison Shari L. , Herschell Amy D. , Karpov Irina O. , MacDonald-Wilson Kim L. 
Published: May 2023

Purpose of Study:
Gatekeeper training for individuals who may be in contact with someone contemplating suicide is a recommended suicide prevention strategy. This study assessed organizational-level gatekeeper training.

Primary Care Setting(s):
Gatekeeper training was conducted in a behavioral health managed care organization (BHMCO), which facilitates integrated behavioral and physical health services for 1.4 million Medicaid-enrolled Pennsylvanians.

Methodology and Sample:
Gatekeeper training was offered to BHMCO staff via a new training policy. Gatekeeper trainers were qualified BHMCO staff. Approximately half (47%) of trained staff served as care managers. Pre- and posttraining surveys were administered to assess self-reported confidence in ability to identify and assist individuals at risk for suicide. Post-training, staff responded to a hypothetical vignette involving suicide risk, which was evaluated for skills by gatekeeper trainers.

Results:
Eighty-two percent of staff completed training. Mean confidence scores improved significantly from pre- (η = 615) to posttraining (η = 556) (understanding = 3.41 vs. 4.11, respectively; knowledge = 3.47 vs. 4.04; identification = 3.30 vs. 3.94; respond = 3.30 vs. 4.04, p < .0001 for each). Intermediate and advanced skills to address suicide risk were demonstrated post-training in 68.6% and 17.2% of staff, respectively. More care managers versus other BHMCO staff demonstrated advanced skills (21.6% vs. 13.0%); however, both groups showed significant improvement pre- to post-training.

Implications for Case Management:
Care managers benefit from suicide prevention training and are uniquely positioned to serve as organizational leaders to successful population health initiatives to decrease suicide through training and education.
Distinct trajectories of caregiver–toddler physiological attunement during routine vaccinations
Authors: Di Lorenzo-Klas Miranda G. , Waxman Jordana A. , Flora David B. , Schmidt Louis A. , Garfield Hartley , Flanders Dan , Weinberg Eitan , Savlov Deena , Pillai Riddell Rebecca R. 
Published: May 2023

Abstract

Introduction:
Toddlers rely on their caregivers for regulatory support when faced with pain-related distress. The caregiver's ability to support their toddler relies on their capacity to regulate their own distress and respond effectively to the child's need for support. The aim of the current study was to describe patterns of caregiver–toddler physiological co-regulatory patterns, also known as attunement, during routine vaccinations across the second year of life.

Methods:
Caregiver–toddler dyads (N = 189) were part of a longitudinal cohort observed at either 12-, 18-, or 24-month well-baby vaccinations. Parallel-process growth-mixture modeling was used to examine patterns of dyadic physiological co-regulatory responses, indexed by high-frequency heart rate variability (HF-HRV).

Results:
Three groups of dyads were discerned. The largest group (approximately 80%) demonstrated physiological attunement, with a stable and parallel regulatory pattern of HF-HRV from baseline to postneedle. The second group (7.9%) had parallel regulatory trajectories but with notably lower (ie, less regulated) HF-HRV values, which indicates independent regulatory responses (ie, a lack of attunement among dyad members). The third group (11.1%) showed diverging regulatory trajectories: Caregivers showed a stable regulatory trajectory, but toddlers demonstrated a steep decrease followed by an increase in HF-HRV values that surpassed their baseline levels by the third minute postneedle. Post hoc analyses with the HF-HRV groupings explored heart rate patterns and potential predictors.

Conclusions:
These findings elucidate potential adaptive and maladaptive co-regulatory parasympathetic patterns in an acute pain context.
Gluteal Fold: Cadaveric Dissection of the Superficial Fascial System in the Buttock and Anatomy-Based Gluteal Liposculpture
Authors: Si Loubin , Li Zhijin , Fu Lin , Zhang Mingzi , Tian Tong , Qi Zheng , Long Xiao , Wang Xiaojun , Wang Yang 
Published: May 2023

Background:
The anatomy and formation mechanism of the gluteal fold (GF) remain unclear. Given that understanding the anatomy of the superficial fascial system (SFS) may facilitate the improvement of liposuction techniques, this study aimed to clarify and define the anatomical components of the GF.

Methods:
A total of 20 fresh female buttocks and thighs were dissected sagittally to observe the changes of the SFS along the GF and were dissected horizontally to observe the SFS on the upper, middle, and lower levels of the buttock.

Results:
Through these dissections, 2 patterns of the SFS in the GF region were identified. The retinaculum cutis (RC)-dominant SFS, named the fascial condensation zone, features an extremely dense and tough RC, originating from the bony structures (eg, the ischium) and radially anchored by the dermis. The fat-dominant SFS features a classic double-layered SFS structure. The RC-dominant SFS is mainly distributed at the medial GF, thus forming the depressed fold. It gradually disappears along the GF and the SFS becomes fat-dominant, making the fold increasingly less visible. At the lateral buttock, the SFS of the buttock and thigh reach an identical status in terms of morphologic features, showing a smooth curve between the buttock and the thigh instead of a fold. Thus, based on these findings, different liposuction methods were formulated to manage GF contouring.

Conclusions:
The SFS of the GF region shows a regional variation pattern. Topographic anatomy of the SFS in the GF region helps us understand GF contour deformities and provide an anatomical basis for surgical correction.
Role of the Medial Canthus Fibrous Band in Forming Moderate and Severe Epicanthal Folds in Asians and Its Clinical Application
Authors: Wang Shimeng , Liu Haipeng , Li Tian , Zhang Duo 
Published: May 2023

Background:
Epicanthal folds (EFs) are skin folds located at the medial canthus in Asians. However, the anatomical structure of EFs remains unclear. The authors discovered a fibrous band connected to the medial canthal tendon (MCT) and referred to it as the medial canthal fibrous band (MCFB). This study aimed to verify whether the MCFB is different from the MCT and whether its unique anatomical relationship with the MCT plays an important role in EF formation.

Methods:
Forty patients who underwent epicanthoplasty from February of 2020 to October of 2021 were included. EFs from 11 patients underwent biopsy and were stained with hematoxylin and eosin, Masson trichrome, and Weigert stains to reveal their composition. Expression of collagens I and III and elastin was determined through immunohistochemical staining, and their mean optical density was measured. Preoperative and immediate exposed lacrimal caruncle area (ELCA) was measured after removing the MCFB.

Results:
The MCFB is a fibrous tissue located in the EF and above the MCT. The orientation and composition of collagen fibers of the MCFB are different from those of the MCT (P < 0.001). The MCFB also has more elastin fibers than the MCT (P < 0.05). Immediate ELCA was significantly higher than before ELCA (P < 0.001) once the MCFB was removed.

Conclusions:
The MCFB is composed of collagen fibers different from those in the MCT and plays a role in EF formation. Removing the MCFB during epicanthoplasty can result in a more attractive appearance postoperatively.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Minimally Invasive Video-Assisted Submuscular Gluteal Augmentation with Implants: An Innovative Technique
Authors: Ibarra-Hurtado Tomás R. , Nuño-Guzmán Carlos M. , Ambriz-Plascencia Ana R. , Ibarra-Tapia María E. 
Published: May 2023

Summary:
Gluteal augmentation is one of the most requested cosmetic procedures. This article describes the surgical technique and early results of an innovative minimally invasive video-assisted submuscular gluteal augmentation with implants. The authors aimed to perform a technique that would reduce complications and surgical time. Fourteen healthy women without obesity or relevant pathologic background who requested gluteal augmentation with implants as a single procedure were included. The procedure was performed through bilateral parasacral 5-cm incisions at cutaneous and subcutaneous planes as far as the gluteus maximus muscle fascia. Through a 1-cm incision in the fascia and muscle, the index finger was introduced under the gluteus maximus, and a submuscular space was created by blunt dissection toward the greater trochanter to avoid a sciatic nerve injury, until the middle gluteus level was reached. Next, the balloon shaft of a Herloon trocar was introduced in the dissected space. Balloon dilatation in this submuscular space was performed as required. The balloon shaft was replaced by the trocar, through which a 30-degree 10-mm laparoscope was introduced. Submuscular pocket anatomic structures were observed, and while the laparoscope was being retrieved, hemostasis was verified. The submuscular plane collapsed, leaving the pocket for the implant to be placed. There were no intraoperative complications. The only postoperative complication was a self-limited seroma in one patient (7.1%). This innovative technique was simple to perform and safe, allowing direct visualization and hemostasis, with a short surgical time, low complication rate, and high degree of satisfaction.
Lip Lifting: The Missing Link in Central Facial Rejuvenation
Authors: Jalalabadi Faryan , Lisiecki Jeffrey L. , Chiodo Michael V. , Rohrich Rod J. 
Published: May 2023

Summary:
The lip lift is a powerful yet finesse operation in the realm of facial rejuvenation. In an era of increased popularity of nonsurgical lip augmentation, the astute plastic surgeon must identify which patients will end up with an unnatural appearance should they receive volume enhancement alone in pursuit of central facial and perioral rejuvenation. In this article, the authors review the ideal youthful lip appearance, characteristics of the aged lip appearance, and indications for lifting. The authors present their preferred surgical technique, the underlying principles that it respects, and adjunct procedures to optimize results in central facial rejuvenation.