bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome—a feasibility study
Authors: Schubert-Hjalmarsson Elke , Fasth Anders , Ickmans Kelly , Mårdbrink Eva-Lott , Söderpalm Ann-Charlott , Lundberg Mari 
Published: June 2023

Abstract
Background
Pain is a major symptom in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the underlying mechanism causing generalized pain in children with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome is unclear, central sensitization has been suggested as a possible explanation. The aim of this study was to explore the feasibility of a study protocol for a future case–control study, investigating features of central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome.

Methods
Central sensitization features were measured in ten patients and nine healthy controls aged 13–17 years via experimental pain measurement quantifying primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia. Descriptive statistics were used. Frequency, median, and range values were calculated.

Results
Eleven out of 57 patients chose to participate. No control could be recruited through public schools. Therefore, a convenience sampling strategy was used for the recruitment of the control group. The process of assessing primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia was well tolerated by all participants (patients and controls). When assessing endogenous pain modulation via conditioned pain modulation, two participants in the patient group and three in the control group did not achieve a pain experience ≥ 3 on the numerical rating scale when immersing their hands in cold water.

Conclusion
This study investigated the feasibility, safety, and toleration of experimental pain measurements in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the test protocol proved to be sufficiently feasible for use with the participant group, it will need to be adapted in the main study in order to obtain more reliable data. Recruitment, especially of participants for the control group, can be a major obstacle for future studies and requires careful planning.

Trial registration
Researchweb.org, 270,501. Registered on 9 May 2019.
Pneumatic vitreolysis versus vitrectomy for the treatment of vitreomacular traction syndrome and macular holes: complication analysis and systematic review with meta-analysis of functional outcomes
Authors: Quiroz-Reyes Miguel A. , Quiroz-Gonzalez Erick A. , Quiroz-Gonzalez Miguel A. , Lima-Gomez Virgilio 
Published: June 2023

AbstractBackgroundWe conducted a systematic review to compare the effects of pneumatic vitreolysis (PV), enzymatic vitreolysis (EVL) with ocriplasmin, and pars plana vitrectomy (PPV) on vitreomacular traction (VMT) syndrome and macular holes (MHs) to assess their efficacy as treatment options.MethodsDatabases, including PubMed, ClinicalTrials.gov (www.clinicaltrials.gov), the Cochrane Central Register of Controlled Trials (CENTRAL)—including the Cochrane Eyes and Vision Group Trials Register (The Cochrane Library2013, Issue 2)—, Ovid MEDLINE, and EMBASE (January 2000–October 2022), were searched to identify studies comparing the outcomes of PV versus PPV, PPV versus ocriplasmin and ocriplasmin versus PV. RevMan 5.1 was used for the meta-analysis of the studies.ResultsAmong the 89 studies, 79 were considered eligible for qualitative analysis, and 10 quantitative studies were subjected to meta-analysis. PPV resulted in better postoperative visual acuity improvement than ocriplasmin (standardized mean deviation (SMD) = 0.38, 95% CI 0.03–0.73,p = 0.0003). PV resulted in no significant difference in visual improvement compared with PPV (SMD = − 0.15, 95% CI − 0.47 to 0.16,p = 0.35). PPV was significantly more effective in terms of the VMT release rate (risk ratio = 0.48, 95% CI 0.38–0.62,p = 0.00001) and MH closure rate (risk ratio = 0.49, 95% CI 0.30–0.81,p = 0.006) than ocriplasmin. PV was more effective than ocriplasmin in terms of the VMT release rate (risk ratio = 0.49, 95% CI 0.35–0.70,p = 0.0001). Qualitative analysis showed MH closure rates of 46%, 47.8%, and 95% and VMT releases rates of 46%, 68% and 100% after ocriplasmin, PV, and PPV treatments, respectively. Adverse events and postoperative complications occurring after treatment have also been documented in these studies.ConclusionPPV appears to be the most promising option for MH closure and VMT release, with fewer serious complications than EVL or PV. However, given the limited number of studies comparing these treatments, further research is needed to establish the superiority of PPV over the other options.
The correlation between coronary artery, aortic, and mitral valve calcification in patients with coronary atherosclerosis
Authors: Suwita Benedicta Mutiara , Suroyo Indrati , Rusdi Lusiani , Prihartono Joedo 
Published: June 2023

Abstract
Background
Atherosclerosis is the underlying process causing coronary artery calcification. Pathophysiology of aortic and mitral valve calcification has several similarities with coronary atherosclerosis, but their correlation has not been clear, especially in patients with coronary atherosclerosis.

Purpose
This study aims to investigate the correlation between the calcium score of the coronary arteries, aortic, and mitral valves in patients with coronary atherosclerosis.

Methods
This was a cross-sectional, correlation study. Stratified randomization was done based on the coronary artery calcium score category. The calcium score was calculated using Agatston technique. Statistical tests were done to look for the correlations between the coronary artery and aortic valve calcium score, coronary artery and mitral valve calcium score, as well as coronary artery and aortic + mitral valve calcium score.

Results
There are ninety-seven subjects (coronary calcium score “mild” 34 subjects, “moderate” 30 subjects, “severe” 33 subjects) with a mean age of 63.85 (± 9.80) years old. The median coronary artery calcium score was 158.7 (Agatston Unit (AU; 1–3917.7), aortic valve 12.6 AU (0–3747), and mitral valve 0.1 AU (0–1247.5 AU). There was a very weak correlation between coronary artery calcium score with aortic, mitral, and aortic + mitral valve calcium score.

Conclusions
There was no statistically significant correlation between the calcium score of the coronary artery and the calcium score of the aortic valve, as well as the calcium score of the mitral valve in patients with coronary atherosclerosis. However, the secondary analysis showed a correlation between them varied depending on the severity of coronary artery calcification, which could shed light on a better understanding of the atherosclerotic process in the coronary artery, aortic, and mitral valve.
Knowledge and utilization of standardized stroke outcome measures among physiotherapists in tertiary health institutions in Anambra State, Nigeria
Authors: Okonkwo Uchenna Prosper , Eze Chidinma Chisom , Ibeneme Sam Chidi , Igwe Sylvester Emeka , Chukwuemeka Uchechukwu Martha , Ihegihu Ebere Yvonne , Ugwuanyi Daniel Chimuanya 
Published: June 2023

Abstract
Background
Knowledge and utilization of standardized stroke outcome measures (SOMs) are important as it helps in the evaluation of patient response to therapy and decision of further step in patient care. This study evaluated the current knowledge and utilization of standardized stroke outcome measures and the factors that influence them.

Methods
A cross-sectional survey research design was used for the study. The consecutive sampling technique was used to recruit 40 (16 females and 24 males) respondents from two tertiary hospitals located in Anambra State. Data were analyzed using the IBM Statistical Package for the Social Sciences (SPSS) version 21. The frequency counts and percentages, mean and standard deviation, chi-square test, and Spearman rank-order correlation were used in the analysis of different variables. The alpha level was set at 0.05.

Results
A total of 37.5% had poor knowledge, 30% had fair knowledge, and 32.5% had good knowledge of SOMs. The highest familiarity (i.e., very familiar) was observed as follows: 6-min walk test (72.5%), Modified Ashworth Scale (70%), Barthel Index (65.75%), Mini-mental Stroke Examination (52.5%), Functional Independence Measure (65%), Berg Balance Scale (50%), and National Institute of Health Stroke Scale (50%). Poor utilization was observed in % of the respondents, fair utilization was observed in 25%, and good was observed in 20% of them. There was a positive correlation between knowledge and utilization of standardized stroke outcome measures (p < 0.01). Knowledge and utilization were each significantly associated with gender and educational qualification. Utilization alone was significantly associated with years of experience and the center of practice.

Conclusion
There is still a deficit in the awareness and utilization of standardized stroke outcome measures in the study population. There has not been an appreciable improvement in the knowledge of SOMs among the population of physiotherapists that participated in the current study. However, the utilization of SOMs is still at a low level. This requires action from critical stakeholders in Nigeria’s health system to encourage its regular use in clinical practice as it will serve to improve service delivery to patients.
Reconciling myths and misconceptions about hypnosis with scientific evidence
Authors: Stein Madeline V. , Lynn Steven Jay , Terhune Devin B. 
Published: June 2023

SUMMARYThis issue ofBJPsych Advancesincludes an article on the use of hypnotherapy in psychiatric practice. The article contains a number of errors and misconceptions regarding the characteristics and practice of hypnosis that we address in this commentary.
An online experimental medicine trial on the effect of 28-day simvastatin administration on emotional processing, reward learning, working memory and salivary cortisol in healthy volunteers at risk for depression: OxSTEP protocol
Authors: Waters Shona , De Giorgi Riccardo , Quinton Alice M. G. , Gillespie Amy L. , Murphy Susannah E. , Cowen Philip J. , Harmer Catherine J. 
Published: June 2023

Background
Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing.

Aims
Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness.

Method
This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.
Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial
Authors: Michalski Jeff M. , Winter Kathryn A. , Prestidge Bradley R. , Sanda Martin G. , Amin Mahul , Bice William S. , Gay Hiram A. , Ibbott Geoffrey S. , Crook Juanita M. , Catton Charles N. , Raben Adam , Bosch Walter , Beyer David C. , Frank Steven J. , Papagikos Michael A. , Rosenthal Seth A. , Barthold H. Joseph , Roach Mack , Moughan Jennifer , Sandler Howard M. 
Published: June 2023

PURPOSETo determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer.METHODSMen with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death.RESULTSFive hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT ( P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006).CONCLUSIONCompared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.
Sex and Tumor-Site Differences in the Association of Alcohol Intake With the Risk of Early-Onset Colorectal Cancer
Authors: Jin Eun Hyo , Han Kyungdo , Shin Cheol Min , Lee Dong Ho , Kang Seung Joo , Lim Joo Hyun , Choi Yoon Jin 
Published: June 2023

PURPOSE Given the increasing incidence of early-onset colorectal cancer (CRC; diagnosed before age 50 years) worldwide, it is important to identify modifiable risk factors. We investigated whether alcohol consumption in the young population correlated with an increased early-onset CRC risk that differed by tumor location and sex. PATIENTS AND METHODS We investigated the association between average daily alcohol consumption and the risk of early-onset CRC among 5,666,576 individuals age 20-49 years using data from the Korean National Health Insurance Service (2009-2019). Alcohol consumption levels of nondrinker, light (reference), moderate, and heavy drinker were defined as 0, <10, 10 to <30, and ≥30 g/d for men and 0, <10, 10 to <20, and ≥20 g/d for women, respectively. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs. RESULTS We identified 8,314 incident early-onset CRC cases during the follow-up period. Moderate and heavy drinkers showed an increased risk of early-onset CRC compared with light drinkers (aHR, 1.09 [95% CI, 1.02 to 1.16] and aHR, 1.20 [95% CI, 1.11 to 1.29], respectively). Subgroup analysis by tumor location showed positive dose-response significance for early-onset distal colon and rectal cancers, but not for proximal colon cancer. The dose-response association between drinking frequency and risk of early-onset CRC was significant, with a 7%, 14%, and 27% increased risk for 1-2, 3-4, and ≥5 d/wk compared with nondrinkers, respectively. CONCLUSION Excessive alcohol consumption increases the risk of CRC onset before age 50 years. Thus, effective interventions are required to discourage alcohol consumption among young people and to tailor CRC screening approaches for high-risk individuals.
Extremity Rhabdomyosarcoma—An Integrated Clinicopathologic and Genomic Study to Improve Risk Stratification
Authors: de Traux de Wardin Henry , Xu Bin , Dermawan Josephine K. , Smith Mariel H. , Wolden Suzanne L. , Antonescu Cristina R. , Wexler Leonard H. 
Published: June 2023

PURPOSE Extremity rhabdomyosarcoma (RMS) is associated with a very poor outcome compared with other sites, mainly because of its high incidence of alveolar histology and regional lymph node involvement. To better define prognostic markers in this clinical subset, we investigated our experience of 61 patients with extremity RMS treated at our tertiary cancer center for the past 2 decades. PATIENTS AND METHODS The patients had a median age of 8 years at diagnosis, equal gender distribution, and two-thirds occurred in the lower extremity. Most (85%) patients had FOXO1 fusion–positive alveolar RMS (ARMS), with 70% having a PAX3::FOXO1 transcript. Remaining were seven patients with fusion-negative embryonal RMS (ERMS) and two with MYOD1-mutant spindle cell/sclerosing RMS (SRMS). In 40% of the patients, material was available for DNA-based targeted sequencing using MSK-IMPACT cancer gene panel. RESULTS One-third of patients presented with localized disease at diagnosis while the remaining had regional nodal (18%) or distant metastases (51%). Metastatic disease, high-risk group, and age 10 years or older significantly affected the overall survival (OS; hazard ratio [HR], 2.68 [ P = .004], 2.78 [ P = .010] and 2.26 [ P = .034], respectively). Although the presence of metastatic disease had a dismal impact on 5-year EFS and OS (19% and 29%, respectively), nodal involvement had a comparatively lower impact on 5-year EFS and 5-year OS (43% and 66%, respectively). PAX3::FOXO1 ARMS had worse prognosis and afflicted older children compared with PAX7::FOXO1 (HR = 3.45, P = .016). The most common events in the ARMS group included MED12 alterations, CDK4 amplifications, and CDKN2A deletions (8%-17%). The latter two abnormalities were mutually exclusive, enriched for acral and high-risk lesions, and correlated with poor outcome on OS ( P = .02). CONCLUSION Our data provide rationale for considering the integration of molecular abnormalities to refine risk stratification in extremity RMS.
Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With ERBB2 Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study
Authors: Ganti Apar K. , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Dib Elie G. , Duvivier Herbert L. , Ahn Eugene R. , Behl Deepti , Borghaei Hossein , Balmanoukian Ani S. , Gaba Anu , Li Rui , Osei-Boateng Kwabena , Thota Ramya , Grantham Gina N. , Gregory Abigail , Halabi Susan , Schilsky Richard L. 
Published: June 2023

PURPOSE The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and ERBB2 mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2 mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival. RESULTS Twenty-eight patients with lung cancer (27 non–small-cell, 1 small-cell) and ERBB2 mutation (n = 15), ERBB2 amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two ERBB2 mutation; one both mutation and amplification) and seven patients with SD16+ (five ERBB2 mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; P = .005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T. CONCLUSION Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non–small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations.
No-cost meals might not exist for insects feeding on toxic plants
Authors: Pokharel Prayan 
Published: June 2023

ABSTRACTPlants produce chemicals (or plant specialised/secondary metabolites, PSM) to protect themselves against various biological antagonists. Herbivorous insects use plants in two ways: as a food source and as a defence source. Insects can detoxify and sequester PSMs in their bodies as a defence mechanism against predators and pathogens. Here, I review the literature on the cost of PSM detoxification and sequestration in insects. I argue that no-cost meals might not exist for insects feeding on toxic plants and suggest that potential costs could be detected in an ecophysiological framework.
The inner mitochondrial membrane fission protein MTP18 serves as a mitophagy receptor to prevent apoptosis in oral cancer
Authors: Panigrahi Debasna P. , Praharaj Prakash P. , Behera Bishnu P. , Patra Srimanta , Patil Shankargouda , Patro Birija S. , Bhutia Sujit K. 
Published: June 2023

ABSTRACT
MTP18 (also known as MTFP1), an inner mitochondrial membrane protein, plays a vital role in maintaining mitochondrial morphology by regulating mitochondrial fission. Here, we found that MTP18 functions as a mitophagy receptor that targets dysfunctional mitochondria into autophagosomes for elimination. Interestingly, MTP18 interacts with members of the LC3 (also known as MAP1LC3) family through its LC3-interacting region (LIR) to induce mitochondrial autophagy. Mutation in the LIR motif (mLIR) inhibited that interaction, thus suppressing mitophagy. Moreover, Parkin or PINK1 deficiency abrogated mitophagy in MTP18-overexpressing human oral cancer-derived FaDu cells. Upon exposure to the mitochondrial oxidative phosphorylation uncoupler CCCP, MTP18[mLIR]-FaDu cells showed decreased TOM20 levels without affecting COX IV levels. Conversely, loss of Parkin or PINK1 resulted in inhibition of TOM20 and COX IV degradation in MTP18[mLIR]-FaDu cells exposed to CCCP, establishing Parkin-mediated proteasomal degradation of outer mitochondrial membrane as essential for effective mitophagy. We also found that MTP18 provides a survival advantage to oral cancer cells exposed to cellular stress and that inhibition of MTP18-dependent mitophagy induced cell death in oral cancer cells. These findings demonstrate that MTP18 is a novel mitophagy receptor and that MTP18-dependent mitophagy has pathophysiologic implications for oral cancer progression, indicating inhibition of MTP18-mitophagy could thus be a promising cancer therapy strategy.