bluuebunny/crossref_metadata_2025 huggingface dataset:
Femoral Physeal-Sparing ACL Reconstruction With Iliotibial Band Autograft Over-the-Top With Associated Lateral Extra-Articular Tenodesis
Authors: Grandberg Camila , Fox Michael A. , Engler Ian D. , Cong Ting , Musahl Volker , McClincy Michael P.
Published: May 2023

Background:

Injuries to the anterior cruciate ligament (ACL) in the pediatric population have been exponentially increasing over the years. However, surgical techniques typically employed for ACL reconstruction (ACL-R) in adults may injure the physes of skeletally immature patients, resulting in growth disturbances.

Indications:

Currently, ACL-R is recommended for most patients, aiming to return the patient to their previous activities as well as reduce the risk of further instability, meniscal and chondral injuries, and early osteoarthritis. Pediatric ACL-R techniques may vary widely. In this video, the technique chosen was over-the-top on the femur with a vertical tibial tunnel, in addition to a lateral extra-articular tenodesis, using the iliotibial (IT) band as the graft.

Technique Description:

The patient is positioned in standard supine arthroscopic position. An incision is made over the lateral epicondyle and the IT band is exposed. A 2-cm-wide graft is harvested. The proximal aspect of the graft is truncated as high as possible, and the distal aspect is left attached to Gerdy tubercle. Arthroscopic portals are established, and the remanent ACL is debrided, exposing the posterior aspect of the lateral femoral condyle. The capsule is penetrated using a Schnidt tonsil to establish the over-the-top position, which is subsequently exchanged for a cardiac clamp. The graft sutures are grasped using the clamp and pulled into the joint. The tibial tunnel is drilled at the anatomic footprint of the ACL. The graft is threaded over-the-top of the lateral femoral condyle and through the tibial tunnel. Finally, femoral graft fixation is performed on the lateral femoral condyle using interrupted sutures through the IT band and periosteum, and tibial graft fixation is performed with standard interference fixation.

Results:

Previous literature shows low re-rupture rates, excellent postoperative patient-reported outcomes, and high return to sport rates.

Conclusion:

In the pediatric population, there is still no ACL-R technique defined as the gold standard. The described technique is a valuable option for ACL-R in skeletally immature patients, with low revision rates and excellent postoperative outcomes. In addition, this technique minimizes the risk of growth disturbances and effectively stabilizes the knee, allowing patients to return to previous activities.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Model selection and robust inference of mutational signatures using Negative Binomial non-negative matrix factorization
Authors: Pelizzola Marta , Laursen Ragnhild , Hobolth Asger
Published: May 2023

Background

The spectrum of mutations in a collection of cancer genomes can be described by a mixture of a few mutational signatures. The mutational signatures can be found using non-negative matrix factorization (NMF). To extract the mutational signatures we have to assume a distribution for the observed mutational counts and a number of mutational signatures. In most applications, the mutational counts are assumed to be Poisson distributed, and the rank is chosen by comparing the fit of several models with the same underlying distribution and different values for the rank using classical model selection procedures. However, the counts are often overdispersed, and thus the Negative Binomial distribution is more appropriate.

Results

We propose a Negative Binomial NMF with a patient specific dispersion parameter to capture the variation across patients and derive the corresponding update rules for parameter estimation. We also introduce a novel model selection procedure inspired by cross-validation to determine the number of signatures. Using simulations, we study the influence of the distributional assumption on our method together with other classical model selection procedures. We also present a simulation study with a method comparison where we show that state-of-the-art methods are highly overestimating the number of signatures when overdispersion is present. We apply our proposed analysis on a wide range of simulated data and on two real data sets from breast and prostate cancer patients. On the real data we describe a residual analysis to investigate and validate the model choice.

Conclusions

With our results on simulated and real data we show that our model selection procedure is more robust at determining the correct number of signatures under model misspecification. We also show that our model selection procedure is more accurate than the available methods in the literature for finding the true number of signatures. Lastly, the residual analysis clearly emphasizes the overdispersion in the mutational count data. The code for our model selection procedure and Negative Binomial NMF is available in the R package SigMoS and can be found at https://github.com/MartaPelizzola/SigMoS.
Comparison of CG, CKD-EPI[AS] and CKD-EPI[ASR] equations to estimate glomerular filtration rate and predict mortality in treatment naïve people living with HIV in Zimbabwe
Authors: Hunter-Dickson Mitchell , Drak Douglas , Anderson Matthew , Shamu Tinei , Chimbetete Cleophas , Dahwa Rumbidzai , Gracey David M.
Published: May 2023

Background

Renal impairment in people living with HIV (PWH) in Sub-Saharan Africa is common and associated with increased morbidity and mortality. The ideal equation to estimate glomerular filtration rate (eGFR) in this population remains unclear. That which best predicts clinical risk may be the most appropriate while validation studies are awaited. Here we compare the Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI[ASR]) and the CKD-EPI equation with the race coefficient removed (CKD-EPI[AS]), in a population of anti-retroviral therapy (ART) naïve PWH in Zimbabwe to assess which equation best predicts mortality.

Methods

A retrospective cohort study of treatment naïve PWH at the Newlands Clinic in Harare, Zimbabwe was completed. The study included all patients commencing ART between 2007 and 2019. Predictors of mortality were assessed by multivariable logistic regression.

Results

A total of 2991 patients were followed-up for a median of 4.6 years. The cohort was 62.1% female, with 26.1% of patients having at least one comorbidity. The CG equation identified 21.6% of patients as having renal impairment compared with 17.6% with CKD-EPI[AS] and 9.3% with CKD-EPI[ASR]. There was a mortality rate of 9.1% across the study period. The highest mortality risk was seen in those with renal impairment as determined by the CKD-EPI[ASR] equation for both eGFR < 90 and eGFR < 60 with OR 2.97 (95%CI 1.86–4.76) and OR 10.6 (95%CI 3.15–18.04) respectively.

Conclusion

In treatment naïve PWH in Zimbabwe, the CKD-EPI[ASR] equation identifies patients at highest risk of mortality when compared to the CKD-EPI[AS] and CG equations.
The effects of community-based interventions on the uptake of selected maternal and child health services: experiences of the IMCHA project in Iringa Tanzania, 2015‐2020
Authors: Maluka Stephen Oswald , Mpambije Chakupewa Joseph , Kamuzora Peter Clever , Fitzgerald Sian
Published: May 2023

Background

Maternal and child health (MCH) improvement has been prioritised in resource-constrained countries. This is due to the desire to meet the global sustainable development goals of achieving a maternal mortality rate of 70 per 100000 live births by 2030. The uptake of key maternal and child health services is crucial for reducing maternal and child health mortalities. Community-Based Interventions (CBIs) have been regarded as among the important strategies to improve maternal and child health service uptake. However, a paucity of studies examines the impacts of CBIs and related strategies on maternal and child health. This paper unveils the contribution of CBIs toward improving MCH in Tanzania.

Methods

Convergent mixed method design was employed in this study. Questionnaires were used to examine the trajectory and trend of the selected MCH indicators using the baseline and end-line data for the implemented CBI interventions. Data was also collected through in-depth interviews and focus group discussions, mainly with implementers of the interventions from the community and the implementation research team. The collected quantitative data was analysed using IBM SPSS, while qualitative data was analysed thematically.

Results

Antenatal care visits increased by 24% in Kilolo and 18% in Mufindi districts, and postnatal care increased by 14% in Kilolo and 31% in Mufindi districts. Male involvement increased by 5% in Kilolo and 13% in Mufindi districts. The uptake of modern family planning methods increased by 31% and 24% in Kilolo and Mufindi districts, respectively. Furthermore, the study demonstrated improved awareness and knowledge on matters pertaining to MCH services, attitude change amongst healthcare providers, and increased empowerment of women group members.

Conclusion

Community-Based Interventions through participatory women groups are vital for increasing the uptake of MCH services. However, the success of CBIs depends on the wide array of contextual settings, including the commitment of implementers of the interventions. Thus, CBIs should be strategically designed to enlist the support of the communities and implementers of the interventions.
The effectiveness of educational program based on health belief model on promotion of puberty health concepts among teen girls: a cross-sectional study in north of Iran
Authors: Eghbal Sedighe Bab , Kenari Zahra Aghaei , Ashouri Asieh , Rouhani-Tonekaboni Nooshin , Kasmaei Parisa , Mehrabian Fardin , Karimy Mahmood , Rezaei Fatemeh , Fattahi Esmaeil
Published: May 2023

Background

Puberty is a sensitive critical stage of human life. As numerous healthy habits and behaviors are created during adolescence, correct health education during puberty is essential to maintain and improve an individual's physical, emotional, and mental health. The present study aimed to determine the impact of educational intervention based on the predictors of the Health Belief Model (HBM) on female nine-grade students’ health behaviors in Rasht, Iran.

Methods

The present randomized controlled trial study examined 110 female nine-grade students. Multi-stage sampling was performed, and the students were randomly divided into two groups of 55 as intervention and control. The data collection tool included a valid and reliable questionnaire with four sections, namely demographic variables, knowledge, HBM constructs, and health behaviors during puberty. The educational program comprised four 45–60-min sessions per group (4 groups of 13) based on HBM. The data were collected two times, before and 1 month after the educational intervention, and were analyzed using the independent t-test, paired t-test, chi-square test, and SPSS 23.

Results

The mean age of menarche was 12.26 ± 1.133 in the intervention group and 12.12 ± 1.263 in the control group. The family was a source of information for students and the main cue to action before the intervention. Before the educational intervention, there was no significant difference between the experimental and control groups in terms of knowledge, HBM constructs, and puberty health behaviors; however, the variables increased significantly in the intervention group after educational intervention (P<0.001).

Conclusions

Given the effectiveness of the HBM in improving the health behavior of adolescent girls, it is recommended that health policymakers should plan and implement educational interventions in this field.
Attitudes of health care professionals towards interprofessional teamwork in Ashanti Region, Ghana
Authors: Dassah Edward T. , Dzomeku Veronica M. , Norman Betty R. , Gyaase Daniel , Opare-Addo Mercy N. A. , Buabeng Kwame O. , Adu-Sarkodie Yaw
Published: May 2023

Background

Interprofessional collaboration ensures that high-quality health care is provided leading to improved health outcomes and provider satisfaction. Assessing the attitudes of health care professionals towards teamwork in Ghana is novel.

Objective

To examine the attitudes of health care professionals towards interprofessional teamwork and assess specific attributes influencing these attitudes in the Ashanti region, prior to implementing an in-service interprofessional HIV training programme.

Methods

A cross-sectional pre-training online survey using a modified Attitudes Toward Health Care Teams Scale was conducted among health care practitioners undergoing a two-day interactive interprofessional HIV training in Kumasi and Agogo from November 2019 to January 2020. Trainees were diverse health professional cadres selected from five hospitals in the Ashanti region of Ghana. Data was summarised using the mean and standard deviation for continuous variables, and frequencies and percentages for categorical variables. An exploratory factor analysis was conducted to categorise the 14 items of the modified attitudes scale. The Wilcoxon rank-sum (Mann–Whitney) and Kruskal–Wallis tests were used to test the mean attitude difference among the demographic characteristics. Statistical significance was set at p < 0.05.

Results

Altogether, 302 health professionals completed the survey. The ages ranged from 20–58 years, mean age 27.96 years (standard deviation 5.90 years). Up to 95% of the trainees agreed with the 14 statements on the modified attitudes scale. Three factors were identified; “quality of care”, “team efficiency”, and “time constraint” with Cronbach’s alpha measures of 0.73, 0.50, and 0.45 respectively. The overall mean attitude score was 58.15 ± 6.28 (95% CI, 57.42–58.88). Attitude of health care professionals towards interdisciplinary teams for patient care varied significantly by age (p = 0.014), health profession cadre (p = 0.005), facility (p = 0.037), and professional experience (p = 0.034).

Conclusion

Strengthening in-service interprofessional training for health practitioners especially early career professionals in the Ashanti region would be valuable.
Effects of weight change on taste function; a systematic review
Authors: Fathi Mojdeh , Javid Ahmad Zare , Mansoori Anahita
Published: May 2023

Background

The aim of this review is to evaluate the relationship between weight status and taste perception and preference of sweet, salt, fat, bitter, and sour through reviewing observational and interventional studies with objective methods.

Methods

A comprehensive literature search was performed in 6 online databases of PubMed, Scopus, Web of Science, Cochrane, Embase, and Google Scholar up to October 2021. The following keywords were used in the search strategy: (Taste OR "Taste Perception" OR "Taste Threshold" OR "Taste preference" OR "Taste sensitivity" OR "Taste changes") AND (weight OR "Weight gain" OR "weight loss" OR "weight change").

Results

Most observational studies indicate that four taste sensitivities or perceptions (especially sweet and salt taste perception) are lower in subjects with overweight and obesity. The longitudinal studies reported that sweet and fat preference is increased along with weight gain in adults. It is concluded that taste perceptions are decreased in individuals with overweight and obesity, especially in men. Also, taste perception and preference change after weight loss but not significantly.

Conclusion

It is suggested that the results of the interventional studies are not conclusive and need further studies with the same and standard design adjusting cofounding variables including genetic, gender, age and food condition of subjects.
KRAS, MYC, and ARF6: inseparable relationships cooperatively promote cancer malignancy and immune evasion
Authors: Sabe Hisataka
Published: May 2023

Mutations in the KRAS gene and overexpression of protein products of the MYC and ARF6 genes occur frequently in cancer. Here, the inseparable relationships and cooperation of the protein products of these three genes in cancer malignancy and immune evasion are discussed. mRNAs encoded by these genes share the common feature of a G-quadruplex structure, which directs them to be robustly expressed when cellular energy production is increased. These three proteins are also functionally inseparable from each other, as follows.　1) KRAS induces MYC gene expression, and may also promote eIF4A-dependent MYC and ARF6 mRNA translation, 2) MYC induces the expression of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and 3) ARF6 protects mitochondria from oxidative injury. ARF6 may moreover promote cancer invasion and metastasis, and also acidosis and immune checkpoint. Therefore, the inseparable relationships and cooperation of KRAS, MYC, and ARF6 appear to result in the activation of mitochondria and the driving of ARF6-based malignancy and immune evasion. Such adverse associations are frequent in pancreatic cancer, and appear to be further enhanced by TP53 mutations.
A comparison between knotted and knotless medial row of suture bridge technique in arthroscopic rotator cuff repair surgery: a meta-analysis
Authors: Xiao Qiuping , Quan Xiaolin , Hu Shidong , Xiao Yujia , Wu Jiangping , Nie Mao
Published: May 2023

Background

The shoulder arthroscopic suture bridge technique is currently very popular, but scientific evidence relating to the clinical outcomes of the medial row with or without knots has not been systematic reviewed.

Purpose

The purpose of this study was to compare the clinical outcomes of knotted versus knotless double-row suture bridges for rotator cuff repairs.

Study design

Meta-analysis.

Method

Five databases that contain literature in English were searched (Medline, PubMed, Embase, Web of Science, and the Cochrane Library), with a focus on works published between 2011 and 2022. Clinical data relating to arthroscopic rotator cuff repair with the suture bridge approach was examined and the outcomes of medial row knotting contrasted with that of the knotless technique. The search phrase used was: (double row) AND (rotator cuff) AND (repair), and the search method is subject term plus free word search. Literature quality evaluation was performed using the Cochrane “risk of bias” tool 1.0 and the Newcastle–Ottawa scale quality assessment instrument.

Results

One randomized controlled trial, four prospective cohort studies, and five retrospective cohort studies were included in this meta-analysis. Data pertaining to 1146 patients was drawn from these ten original papers and analyzed. Meta-analyses that were performed on 11 postoperative outcomes revealed that none of the differences were statistically significant (P > 0.05) and that the publications were unbiased (P > 0.05). Postoperative retear rate and postoperative retear categorization were the outcomes assessed. Scores on postoperative pain, forward flexion, abduction, and external rotation mobility were collated and evaluated. The University of California, Los Angeles scoring systems in the first year following surgery, the American Shoulder and Elbow Surgeons score and Constant scales in the first and second years after surgery were the secondary outcomes spotlighted in this study.

Conclusion

The clinical outcomes of shoulder arthroscopic rotator cuff repair with the suture bridge technique with or without a knotted medial row was proven to be equivalent. These outcomes are about postoperative retear, postoperative retear classification, postoperative shoulder function score, postoperative shoulder mobility, and postoperative pain, respectively. It should be noted that the conclusions are based on short-term clinical follow-up data.
First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors
Authors: Zhao Yuanyuan , Ma Yuxiang , Zang Aimin , Cheng Ying , Zhang Yiping , Wang Xiangcai , Chen Zhendong , Qu Song , He Jianbo , Chen Chuanben , Jin Chuan , Zhu Dongyuan , Li Qingshan , Liu Xianling , Su Wuyun , Ba Yi , Hao Yanrong , Chen Junmin , Zhang Guoping , Qu Shenhong , Li Yong , Feng Weineng , Yang Mengxiang , Liu Baorui , Ouyang Weiwei , Liang Jin , Yu Zhuang , Kang Xiaoyan , Xue Shilin , Yang Guihong , Yan Wei , Yang Yingying , Liu Zhi , Peng Yufeng , Fanslow Bill , Huang Xian , Zhang Li , Zhao Hongyun
Published: May 2023

Background

QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies.

Methods

In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated.

Results

Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3—not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively.

Conclusions

QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials.

Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.
Impact of early relapse within 24 months after first-line systemic therapy (POD24) on outcomes in patients with marginal zone lymphoma: A US multisite study
Authors: Epperla Narendranath , Welkie Rina Li , Torka Pallawi , Shouse Geoffrey , Karmali Reem , Shea Lauren , Anampa-Guzmán Andrea , Oh Timothy S. , Reaves Heather , Tavakkoli Montreh , Lindsey Kathryn , Greenwell Irl Brian , Hansinger Emily , Thomas Colin , Chowdhury Sayan Mullick , Annunzio Kaitlin , Christian Beth , Barta Stefan K. , Geethakumari Praveen Ramakrishnan , Bartlett Nancy L. , Herrera Alex F. , Grover Natalie S. , Olszewski Adam J.
Published: May 2023

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of POD24 and the assessment of cumulative incidence of histologic transformation (HT) in POD24 versus non-POD24 groups. The study included 524 patients with 143 (27%) in POD24 and 381 (73%) in non-POD24 groups. Patients with POD24 had inferior OS compared to those without POD24, regardless of the type of systemic therapy received (rituximab monotherapy or immunochemotherapy) at diagnosis. After adjusting for factors associated with inferior OS in the univariate Cox model, POD24 remained associated with significantly inferior OS (HR = 2.50, 95% CI = 1.53–4.09, p = 0.0003) in multivariable analysis. The presence of monoclonal protein at diagnosis and those who received first-line rituximab monotherapy had higher odds of POD24 on logistic regression analysis. Patients with POD24 had a significantly higher risk for HT compared to those without POD24. POD24 in MZL might be associated with adverse biology and could be used as an additional information point in clinical trials and investigated as a marker for worse prognosis.
Convergence of YAP/TAZ, TEAD and TP63 activity is associated with bronchial premalignant severity and progression
Authors: Ning Boting , Tilston-Lunel Andrew M. , Simonetti Justice , Hicks-Berthet Julia , Matschulat Adeline , Pfefferkorn Roxana , Spira Avrum , Edwards Matthew , Mazzilli Sarah , Lenburg Marc E. , Beane Jennifer E. , Varelas Xaralabos
Published: May 2023

Background

Bronchial premalignant lesions (PMLs) are composed primarily of cells resembling basal epithelial cells of the airways, which through poorly understood mechanisms have the potential to progress to lung squamous cell carcinoma (LUSC). Despite ongoing efforts that have mapped gene expression and cell diversity across bronchial PML pathologies, signaling and transcriptional events driving malignancy are poorly understood. Evidence has suggested key roles for the Hippo pathway effectors YAP and TAZ and associated TEAD and TP63 transcription factor families in bronchial basal cell biology and LUSC. In this study we examine the functional association of YAP/TAZ, TEADs and TP63 in bronchial epithelial cells and PMLs.

Methods

We performed RNA-seq in primary human bronchial epithelial cells following small interfering RNA (siRNA)-mediated depletion of YAP/TAZ, TEADs or TP63, and combined these data with ChIP-seq analysis of these factors. Directly activated or repressed genes were identified and overlapping genes were profiled across gene expression data obtained from progressive or regressive human PMLs and across lung single cell RNA-seq data sets.

Results

Analysis of genes regulated by YAP/TAZ, TEADs, and TP63 in human bronchial epithelial cells revealed a converged transcriptional network that is strongly associated with the pathological progression of bronchial PMLs. Our observations suggest that YAP/TAZ-TEAD-TP63 associate to cooperatively promote basal epithelial cell proliferation and repress signals associated with interferon responses and immune cell communication. Directly repressed targets we identified include the MHC Class II transactivator CIITA, which is repressed in progressive PMLs and associates with adaptive immune responses in the lung. Our findings provide molecular insight into the control of gene expression events driving PML progression, including those contributing to immune evasion, offering potential new avenues for lung cancer interception.

Conclusions

Our study identifies important gene regulatory functions for YAP/TAZ-TEAD-TP63 in the early stages of lung cancer development, which notably includes immune-suppressive roles, and suggest that an assessment of the activity of this transcriptional complex may offer a means to identify immune evasive bronchial PMLs and serve as a potential therapeutic target.
Impact of cardiac output and alveolar ventilation in estimating ventilation/perfusion mismatch in ARDS using electrical impedance tomography
Authors: Tuffet Samuel , Maraffi Tommaso , Lacheny Matthieu , Perier François , Haudebourg Anne-Fleur , Boujelben Mohamed Ahmed , Alcala Glasiele , Mekontso-Dessap Armand , Carteaux Guillaume
Published: May 2023

Introduction

Electrical impedance tomography (EIT) can be used to assess ventilation/perfusion (V/Q) mismatch within the lungs. Several methods have been proposed, some of them neglecting the absolute value of alveolar ventilation (VA) and cardiac output (QC). Whether this omission results in acceptable bias is unknown.

Methods

Pixel-level V/Q maps of 25 ARDS patients were computed once considering (absolute V/Q map) and once neglecting (relative V/Q map) the value of QC and VA. Previously published indices of V/Q mismatch were computed using absolute V/Q maps and relative V/Q maps. Indices computed with relative V/Q maps were compared to their counterparts computed using absolute V/Q maps.

Results

Among 21 patients with ratio of alveolar ventilation to cardiac output (VA/QC) > 1, relative shunt fraction was significantly higher than absolute shunt fraction [37% (24–66) vs 19% (11–46), respectively, p < 0.001], while relative dead space fraction was significantly lower than absolute dead space fraction [40% (22–49) vs 58% (46–84), respectively, p < 0.001]. Relative wasted ventilation was significantly lower than the absolute wasted ventilation [16% (11–27) vs 29% (19–35), respectively, p < 0.001], while relative wasted perfusion was significantly higher than absolute wasted perfusion [18% (11–23) vs 11% (7–19), respectively, p < 0.001]. The opposite findings were retrieved in the four patients with VA/QC < 1.

Conclusion

Neglecting cardiac output and alveolar ventilation when assessing V/Q mismatch indices using EIT in ARDS patients results in significant bias, whose direction depends on the VA/QC ratio value.
Molecular imaging of fibroblast activation in multiple non-ischemic cardiomyopathies
Authors: Wang Jingnan , Huo Li , Lin Xue , Fang Ligang , Hacker Marcus , Niu Na , Li Xiang
Published: May 2023

Background

This pilot study is aimed to perform a pilot visualization study to investigate in vivo fibroblast activation in non-ischemic cardiomyopathies by 68Ga-FAPI-04 PET/CT.

Methods

Twenty-nine consecutive patients with symptomatic non-ischemic cardiomyopathies who underwent 68Ga-FAPI-04 PET/CT were prospectively recruited. Clinical characteristics and echocardiographic parameters were recorded. Cardiac uptake was quantified by standardized uptake values (SUVmax, SUVmean, SUVR) and left ventricular metabolism volume. The relationship between 68Ga-FAPI-04 uptake with clinical and echocardiography parameters was investigated.

Results

Heterogeneous 68Ga-FAPI-04 uptake was observed in different subtypes of non-ischemic cardiomyopathies. Twenty-two (75.9%) patients showed elevated 68Ga-FAPI-04 uptake in the left ventricle, and 10 (34.5%) patients also showed slightly diffuse elevated uptake in the right ventricle. Cardiac uptake values were significantly correlated with enlarged ventricular volume evaluated by echocardiography.

Conclusion

FAPI PET/CT presents a potential value for in vivo visualization and quantification of fibroblast activation on the molecular level. Further study is warranted for investigating the theranostic and prognostic value of elevated FAP signal.
Effects of dietary supplementation of bacteriophage cocktail on health status of weanling pigs in a non-sanitary environment
Authors: Choi YoHan , Hosseindoust Abdolreza , Ha Sang Hun , Kim Joeun , Min YeJin , Jeong YongDae , Mun JunYoung , Sa SooJin , Kim JinSoo
Published: May 2023

Background

The study evaluated the effects of bacteriophage cocktail (BP) and ZnO administered during weaning time for piglets exposed to a non-sanitary environment. The bacteriophages were designed to eliminate Escherichia coli (K88, K99 and F41), Salmonella (typhimurium and enteritidis), and Clostridium perfreingens (types A and C). Forty 21-day-old crossbreed piglets were assigned to four treatments, including the PC (sanitary environment), NC (non-sanitary environment), BP (NC plus 108 pfu/kg BP), and ZO (NC plus 2,500 mg/kg ZnO). Piglets in the NC, BP and ZO were kept in a non-sanitary environment for 14 d, which was contaminated with the feces of infected pigs.

Results

Pigs in the BP and ZO treatments had a higher final body weight compared with the NC. The NC treatment showed the highest concentration of inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α in the plasma. The administration of BP and ZO showed lower myeloperoxidase concentrations compared with the NC. The NC treatment showed a lower concentration of superoxide dismutase in serum compared with the PC. Among the treatments in non-sanitary environment, the NC treatment showed a higher concentration of malondialdehyde compared with the ZO. The PC treatment showed a lower concentration of butyric acid in the feces compared with the BP treatment. Among non-sanitary treatments, the villus height in the duodenum was greater in the BP and ZO compared with the NC. The lower abundance of Proteobacteria phylum was observed in the BP and PC treatments compared with the NC. The highest relative abundance of Eubacterium was recorded in the BP treatment. The abundance of Megasphaera and Schwartzia was higher in the NC pigs compared with the BP piglets. The abundance of Desulfovibrio was lower in the supplemented treatments (BP and ZO) compared with non-supplemented (NC and PC). The abundance of Cellulosilyticum genera was higher in the BP and ZO treatments rather than in the NC. The piglets in the NC treatment had the highest abundance of Escherichia-Shigella, followed by the PC and ZO treatments.

Conclusion

In conclusion, these results suggest that the supplementation of bacteriophage cocktail could effectively control Proteobacteria phylum, Clostridium spp. and coliforms population and mitigated the adverse influences of weaning stress in piglets.
ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics
Authors: Panahi Mahmod , Hase Yoshiki , Gallart-Palau Xavier , Mitra Sumonto , Watanabe Atsushi , Low Roger C , Yamamoto Yumi , Sepulveda-Falla Diego , Hainsworth Atticus H , Ihara Masafumi , Sze Siu Kwan , Viitanen Matti , Behbahani Homira , Kalaria Raj N
Published: May 2023

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear. Focusing on cerebral microvessels in the frontal and anterior temporal lobes and the basal ganglia, we used advanced proteomic and immunohistochemical methods to explore the extent of inflammatory and immune responses in CADASIL subjects compared to similar age normal and other disease controls. There was variable loss of VSMC in medial layers of arteries in white matter as well as the cortex, that could not be distinguished whether NOTCH3 mutations were in the epidermal growth factor (EGFr) domains 1–6 or EGFr7-34. Proteomics of isolated cerebral microvessels showed alterations in several proteins, many associated with endoplasmic reticulum (ER) stress including heat shock proteins. Cerebral vessels with sparsely populated VSMCs also attracted robust accrual of perivascular microglia/macrophages in order CD45+ > CD163+ > CD68+cells, with > 60% of vessel walls exhibiting intercellular adhesion molecule-1 (ICAM-1) immunoreactivity. Functional VSMC cultures bearing the NOTCH3 Arg133Cys mutation showed increased gene expression of the pro-inflammatory cytokine interleukin 6 and ICAM-1 by 16- and 50-fold, respectively. We further found evidence for activation of the alternative pathway of complement. Immunolocalisation of complement Factor B, C3d and C5-9 terminal complex but not C1q was apparent in ~ 70% of cerebral vessels. Increased complement expression was corroborated in > 70% of cultured VSMCs bearing the Arg133Cys mutation independent of N3ECD immunoreactivity. Our observations suggest that ER stress and other cellular features associated with arteriolar VSMC damage instigate robust localized inflammatory and immune responses in CADASIL. Our study has important implications for immunomodulation approaches to counter the characteristic arteriopathy of CADASIL.
Conformational characterization of the mammalian-expressed SARS-CoV-2 recombinant receptor binding domain, a COVID-19 vaccine
Authors: Moro-Pérez Leina , Boggiano-Ayo Tammy , Lozada-Chang Sum Lai , Fernández-Saiz Olga Lidia , de la Luz Kathya Rashida , Gómez-Pérez Jose Alberto
Published: May 2023

The COVID-19 pandemic has caused a large number of diseases worldwide. There are few vaccines to constrain this disease and the value of them is high. In this sense, the antigens of the vaccine platform Soberana, the receptor binding domain from SARS-CoV-2 Spike protein, both the monomeric (mRBD) and dimeric (dRBD) forms, have been developed. This study encompassed several analyses by different techniques like circular dichroism (CD), fluorescence spectroscopy (FS) and Gel Filtration- High Performance Liquid ChLC of mRBD and dRBD. Monomer and dimer exhibited similar far-UV CD spectral characteristics with 54% of β-sheet content. Similar conformational features according to near-UV CD and FS studies were observed in both RBD. Stress stability studies by far-UV CD, FS, biological activity and GF-HPLC at 37 °C showed that mRBD is very stable. On the other hand, dRBD fluorescent emission showed a shift towards higher wavelengths as the incubation time increases, suggesting exposition of tryptophan residues, unlike what happens with mRBD. Biological activity outcome confirms these results. GF-HPLC profiles showed that in mRBD, the product of molecular stress are dimers and does not increase over time. However, dRBD showed dimer fragmentation as the main degradation species. This study reveals the usefulness of CD techniques for the analysis of degradation of RBD molecules as well as showed the difference in stability of both RBD molecules. Besides, our work provides useful insights into the production of a key protein used in diagnosis and therapeutics to fight COVID-19 pandemia.
Classification of age groups and task conditions provides additional evidence for differences in electrophysiological correlates of inhibitory control across the lifespan
Authors: Goelz Christian , Reuter Eva-Maria , Fröhlich Stephanie , Rudisch Julian , Godde Ben , Vieluf Solveig , Voelcker-Rehage Claudia
Published: May 2023

The aim of this study was to extend previous findings on selective attention over a lifetime using machine learning procedures. By decoding group membership and stimulus type, we aimed to study differences in the neural representation of inhibitory control across age groups at a single-trial level. We re-analyzed data from 211 subjects from six age groups between 8 and 83 years of age. Based on single-trial EEG recordings during a flanker task, we used support vector machines to predict the age group as well as to determine the presented stimulus type (i.e., congruent, or incongruent stimulus). The classification of group membership was highly above chance level (accuracy: 55%, chance level: 17%). Early EEG responses were found to play an important role, and a grouped pattern of classification performance emerged corresponding to age structure. There was a clear cluster of individuals after retirement, i.e., misclassifications mostly occurred within this cluster. The stimulus type could be classified above chance level in ~ 95% of subjects. We identified time windows relevant for classification performance that are discussed in the context of early visual attention and conflict processing. In children and older adults, a high variability and latency of these time windows were found. We were able to demonstrate differences in neuronal dynamics at the level of individual trials. Our analysis was sensitive to mapping gross changes, e.g., at retirement age, and to differentiating components of visual attention across age groups, adding value for the diagnosis of cognitive status across the lifespan. Overall, the results highlight the use of machine learning in the study of brain activity over a lifetime.

Graphical Abstract
The PROB-PD trial: a pilot, randomised, placebo-controlled study protocol to evaluate the feasibility and potential efficacy of probiotics in modulating peripheral immunity in subjects with Parkinson’s disease
Authors: Martini Stefano , Marino Franca , Magistrelli Luca , Contaldi Elena , Cosentino Marco , Comi Cristoforo
Published: May 2023

Background

Parkinson’s disease (PD) is a common neurodegenerative disease. No disease-modifying treatment is available, and therapy is symptomatic. The histopathologic hallmark is the loss of dopaminergic neurons and accumulation of α-synuclein (α-syn) in surviving neurons, but the underlying pathophysiology is unclear. Inflammatory mechanisms seem to play a prominent role, with an imbalance of immune functions and neurotoxicity caused by reactive oxygen species (ROS). Involvement of peripheral adaptive immunity, with an imbalance in T cell subpopulations and in the expression of transcriptional factors in CD4+ T cells, has also been reported. Although clinical presentation is defined by motor symptoms, patients also report non-motor symptoms, often before the onset of a clinically established disease. Etiopathogenesis of PD is unknown, but an initial aggregation of α-syn in the gut, with subsequent propagation along the vagus nerve to the brain has been hypothesised. Interestingly, in an α-syn overexpressing murine model, the absence of gut microbiota prevented both microglia activation and motor impairment, thus pointing to a fundamental role of microbiota in the development of PD. Magistrelli et al. showed that in peripheral blood mononuclear cells of PD patients, probiotics modulate the in vitro production of cytokines toward an anti-inflammatory profile and reduce the production of ROS.

Methods

This is a pilot randomised placebo-controlled clinical trial protocol for a 12-week treatment with probiotics. At least 80 patients affected by PD will be recruited and randomly allocated to either the treatment or placebo group in a 1:1 ratio. General inclusion criteria will be the onset of PD 2 to 5 years before the trial and absence of autoimmune comorbidities or immunomodulating therapy. Our primary endpoint is the assessment of changes in extracellular cytokine levels (Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10) and ROS production. Secondary outcomes include changes in lymphocyte subpopulations and transcriptional factors mRNA levels.

Discussion

This study is designed to highlight the potential beneficial role of probiotics administration on peripheral immunity through the modulation of gut microbiota. Explorative outcomes will be evaluated to assess variations in motor and non-motor symptoms and the possible correlation with probiotics administration.

Trial registration

ClinicalTrials.gov ID NCT05173701. Registered 08 November 2021
Immigrants and refugees, tourists and vagabonds: why and how they integrate differently
Authors: Çelik Çetin
Published: May 2023

This paper investigates the integration of immigrants and refugees by drawing on Bauman's conceptual distinction of tourists and vagabonds. Through qualitative interviews with immigrants and refugees in Istanbul, the study highlights differences in their networks, perceptions of the city, the nature and conditions of their stay, and their sense of being welcomed. The study illustrates, differences in resources, status, and the host society's ethno-racial hierarchy result in different adaptation processes. The study's findings contribute to scholarship on ethnicity and migration by comparatively revealing potential variations in refugee integration.
Experimental and numerical study on dynamic stall under a large Reynolds number
Authors: Wei Binbin , Gao Yongwei , Hu Shuling
Published: May 2023

Dynamic stall under large Reynolds numbers and large reduced frequencies has a significant effect on the performance of the wind turbine blades, helicopter rotors, etc. So the dynamic stall physics of the NACA0012 airfoil under a large Reynolds number of Re = 1.5 × 106 was studied using experimental and numerical methods. The reduced frequency range was k = 0.035 – 0.1. The unsteady flow field in dynamic stall was studied in detail by using the transient pressure measurement and the numerical simulation based on the unsteady Reynolds-averaged Navier-Stokes (URANS) equation. And the time-frequency characteristics of the dynamic stall were studied using the wavelet analysis. The study showed that the aerodynamic performance during the dynamic stall was dominated by the shear layer vortex (SLV) and the leading edge vortex (LEV), and the phase difference between the SLV and the LEV was the key factor in the existence of the bimodal characteristics of the aerodynamic force/moment. There was a significant linear correlation between the negative peak of the vortex-induced Cp and the Cn in the reduced frequency range studied in this paper. During the convection of the near-wall LEV to the trailing edge, the high-frequency features firstly decay, and the multi-scale structures of the LEV become more significant as the reduced frequency gradually increases.
Microtaper leaky-mode spectrometer with picometer resolution
Authors: Cen Qingqing , Pian Sijie , Liu Xinhang , Tang Yuwei , He Xinying , Ma Yaoguang
Published: May 2023

The wide application of optical spectroscopy makes miniaturized spectrometers with fundamental importance. The scalability, high-performance, low-cost, and small footprint are still contradicting each other and limiting the applicability of miniaturized spectrometer for practical application. Here we propose a compact spectrometer that satisfies the four advantages. The device uses a fiber taper tip to generate complex leaky mode patterns within 1 mm length. The unique correspondence between the pattern and wavelength operates effectively for hundreds of nanometers spectral range while providing a spectral resolution around ~ 1 pm. The integration of multiple taper tips enables hyperspectral imaging applications. The working range of our device can be further extended using different materials and detectors while keeping the similar architecture.
Structural Sexism and Cancer Care: The Effects on the Patient and Oncologist
Authors: Keenan Bridget P. , Barr Elizabeth , Gleeson Elizabeth , Greenberg Caprice Christian , Temkin Sarah M.
Published: May 2023

Despite progress toward equity within our broad social context, the domains of gender as a social, cultural, and structural variable continue to exert influence on the delivery of oncology care. Although there have been vast advances in our understanding of the biological underpinnings of cancer and significant improvements in clinical care, disparities in cancer care for all women—including cisgender, transgender, and gender diverse women—persist. Similarly, despite inclusion within the oncology physician workforce, women and gender minorities, particularly those with additional identities under-represented in medicine, still face structural barriers to clinical and academic productivity and career success. In this article, we define and discuss how structural sexism influences both the equitable care of patients with cancer and the oncology workforce and explore the overlapping challenges in both realms. Solutions toward creating environments where patients with cancer of any gender receive optimal care and all physicians can thrive are put forward.