bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrum of clonal hematopoiesis in VEXAS syndrome
Authors: Gutierrez-Rodrigues Fernanda , Kusne Yael , Fernandez Jenna , Lasho Terra L , Shalhoub Ruba N , Ma Xiaoyang , Alessi Hugh , Finke Christy M. , Koster Matthew J. , Mangaonkar Abhishek A. , Warrington Kenneth J , Begna Kebede , Xie Zhuoer , Ombrello Amanda K , Viswanatha David S , Ferrada Marcela A. , Wilson Lorena , Go Ronald S. , Kourelis Taxiarchis V. , Reichard Kaaren K , Olteanu Horatiu , Darden Ivana , Hironaka Dalton , Alemu Lemlem , Kajigaya Sachiko , Calado Rodrigo T. , Groarke Emma M. , Rosenzweig Sofia , Kastner Daniel L , Calvo Katherine R , Wu Colin O. , Grayson Peter C. , Young Neal S , Beck David B. , Patel Bhavisha A. , Patnaik Mrinal M.
Published: April 2023

VEXAS is caused by somatic mutations in UBA1 (UBA1mut) and characterized by heterogenous systemic auto-inflammation and progressive hematologic manifestations, meeting criteria for myelodysplastic syndrome (MDS) and plasma cell dyscrasias. The landscape of myeloid-related gene mutations leading to typical clonal hematopoiesis (CH) in these patients is unknown. Retrospectively, we screened 80 VEXAS patients for CH in their peripheral blood (PB) and correlated findings with clinical outcomes in 77. UBA1mutwere most common at hotspot p.M41 (median variant allele frequency/VAF = 75%). Typical CH mutations co-occurred with UBA1mut in 60% of patients, mostly in DNMT3A and TET2, and were not associated with inflammatory or hematologic manifestations. In prospective single-cell proteogenomic sequencing (scDNA), UBA1mutwas the dominant clone, present mostly in branched clonal trajectories. Based on integrated bulk and scDNA analyses, clonality in VEXAS followed two major patterns: with either typical CH preceding UBA1mutselection in a clone (Pattern 1), or occurring as an UBA1mutsubclone or in independent clones (Pattern 2). VAF in PB differed markedly between DNMT3A and TET2 clones (median VAF of 25% vs 1%). DNMT3A and TET2 clones associated with hierarchies representing patterns 1 and 2, respectively. Overall survival for all patients was 60% at 10 years. Transfusion-dependent anemia, moderate thrombocytopenia, and typical CH mutations, each correlated with poor outcome. In VEXAS, UBA1mut cells are the primary cause of systemic inflammation and marrow failure, being a new molecularly defined somatic entity associated with MDS. VEXAS-associated MDS is distinct from classical MDS in its presentation and clinical course.
Alternative donor BMT with post-transplant cyclophosphamide as initial therapy for acquired severe aplastic anemia
Authors: DeZern Amy , Zahurak Marianna L , Symons Heather J , Cooke Kenneth R. , Huff Carol Ann , Jain Tania , Swinnen Lode J , Imus Philip Hollingsworth , Wagner-Johnston Nina D. , Ambinder Richard F , Levis Mark J. , Luznik Leo , Bolaños-Meade Javier , Fuchs Ephraim J , Jones Richard J , Brodsky Robert A.
Published: April 2023

Severe aplastic anemia (SAA) is a marrow failure disorder with high morbidity and mortality. It is treated with bone marrow transplantation (BMT) for those with fully matched donors or immunosuppressive therapy (IST) for those who lack such a donor, which is often the case for underrepresented minorities. We conducted a prospective phase II trial of reduced-intensity conditioning HLA-haplo BMT and post-transplantation cyclophosphamide (PTCy)-based graft-versus-host (GVHD) prophylaxis as initial therapy for patients with SAA. The median age was 25 (range 3-63) years and the median follow-up was 40.9 months (95% CI: 29.4, 55.7 mos). Over 35% of enrollment was from underrepresented racial/ethnic groups. The cumulative incidence of grade II-IV aGVHD at day 100 is 7% (95% CI: NA, 17%) and chronic GVHD at 2 years is 4% (95% CI: NA, 11%). The overall survival for 27 patients is 92% (95% CI: 83,100%) at one, two, and three years. The first 7 patients received lower dose total body irradiation (200 versus 400 cGY), but these patients were more likely to have graft failure, 3 of 7, compared to 0 out of 20 patients in the higher dose group (p=0.01, Fisher exact). HLA-haploidentical BMT with PTCy using 400cGY total body irradiation resulted in 100% overall survival with minimal GVHD in 20 consecutive patients. Not only does this approach avoid the ramifications of IST and its low failure-free survival, but also the use of haploidentical donors expands access to BMT across all populations. Clinical trial: NCT02833805
Rational design on high-performance triboelectric nanogenerator consisting of silicon carbide@silicon dioxide nanowhiskers/polydimethylsiloxane (SiC@SiO2/PDMS) nanocomposite films
Authors: Zhao Kun , Sun Wanru , Li Suixin , Song Zhenhua , Zhong Ming , Zhang Ding , Gu Bing-Ni , Liu Ming-Jin , Fu Hao , Liu Hongjie , Meng Cheng , Chueh Yu-Lun
Published: April 2023

The relatively low output performance of triboelectric nanogenerator (TENG), which faces a challenge in performance improvement, limits its practical applications. Here, a high-performance TENG consisting of a silicon carbide@silicon dioxide nanowhiskers/polydimethylsiloxane (SiC@SiO2/PDMS) nanocomposite film and a superhydrophobic aluminum (Al) plate as triboelectric layers is demonstrated. The 7 wt% SiC@SiO2/PDMS TENG presents a peak voltage of 200 V and a peak current of 30 μA, which are ~ 300 and ~ 500% over that of the PDMS TENG, owing to an increase in dielectric constant and a decrease in dielectric loss of the PDMS film because of electric insulated SiC@SiO2 nanowhiskers. Furthermore, a 10 μF capacitor can be charged up to 3 V within ~ 87 s, which can be continuously operated on the electronic watch for 14 s. The work provides an effective strategy for improving output performance of TENG by adding core–shell nanowhiskers to modulate the dielectric properties of organic materials.

Graphical abstract
Dose–response prediction for in-vitro drug combination datasets: a probabilistic approach
Authors: Rønneberg Leiv , Kirk Paul D. W. , Zucknick Manuela
Published: April 2023

In this paper we propose PIICM, a probabilistic framework for dose–response prediction in high-throughput drug combination datasets. PIICM utilizes a permutation invariant version of the intrinsic co-regionalization model for multi-output Gaussian process regression, to predict dose–response surfaces in untested drug combination experiments. Coupled with an observation model that incorporates experimental uncertainty, PIICM is able to learn from noisily observed cell-viability measurements in settings where the underlying dose–response experiments are of varying quality, utilize different experimental designs, and the resulting training dataset is sparsely observed. We show that the model can accurately predict dose–response in held out experiments, and the resulting function captures relevant features indicating synergistic interaction between drugs.
A qualitative study of the interaction experiences between family caregivers and community nurses for disabled elderly people at home
Authors: Guo Panpan , Zhang Shanfeng , Niu Meilan , Wang Panpan , Li Ling , Wu Chuqiao , Zhao Di , Ma Rui , Wang Peng
Published: April 2023

Background

Family members are currently the main caregivers of the disabled elderly people at home. With declining health and increasing frailty, caregiving of disabled elderly people becomes a task of family caregivers in conjunction with community nurses. Interaction between family caregivers and community nurses can effectively improve the quality of home care for the disabled elderly people. This study aimed to investigate the interaction experiences between family caregivers and community nurses for disabled elderly people at home.

Methods

This research was a study of qualitative descriptions based on semi-structured face-to-face interviews. This study was to purposefully select family caregivers of the disabled elderly and community nurses in Zhengzhou city, Henan Province and explore the interaction patterns between them. Directed content analysis method was used to generate qualitative codes and identify themes.

Results

A total of 12 interviews were completed, including 7 family caregivers and 5 community nurses. Four themes were identified: 1) Information interaction; 2) Emotional interaction; 3) Practical interaction; 4) Factors that promote and hinder the interaction.

Conclusions

It was found that the interaction between family caregivers and community nurses was not optimistic. Lack of communication and collaboration between community nurses and caregivers. Providing a new perspective that we can develop and implement intervention to facilitate positive interactions, which will reduce the burden of family caregivers, bring the highest quality of care to older adults with disabilities and improve the quality of care for disabled elderly people.

Trial registration

Registered in the Chinese Clinical Trial Registry on April 19, 2021, number ChiCTR2100045584.
Proteomic profiling of protein expression changes after 3 months-exercise in ESRD patients on hemodialysis
Authors: Jeong Hye Yun , An Hyun-Ju , Sung Min Ji , Ha Min Heui , Lee Yu Ho , Yang Dong Ho , Yang Tae Young , Han Dohyun , Lee So-Young
Published: April 2023

The prevalence of chronic kidney disease (CKD) is steadily increasing, and it is a global health burden. Exercise has been suggested to improve physical activity and the quality of life in patients with CKD, eventually reducing mortality. This study investigated the change in physical performance after exercise in dialysis-dependent patients with CKD and analyzed differentially expressed proteins before and after the exercise. Plasma samples were collected at enrollment and after 3 months of exercise. Liquid chromatography with tandem mass spectrometry analysis and data-independent acquisition results were analyzed to determine the significantly regulated proteins. A total of 37 patients on dialysis were recruited, and 16 were randomized to exercise for 3 months. The hand grip strength and the walking speed significantly improved in the exercise group. Proteome analysis revealed 60 significantly expressed proteins after 3 months of exercise. In the protein functional analysis, the significantly expressed proteins were involved in the immune response. Also, some of the key significantly expressed proteins [(M Matrix metallopeptidase 9 (MMP-9), Activin A Receptor Type 1B (ACVR1B), Fetuin B (FETUB)] were validated via an enzyme-linked immunosorbent assay. Our results showed that exercise in dialysis-dependent patients with CKD could improve their physical performance. These results indicated that this beneficial effect of exercise in these populations could be associated with immune response.
Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays
Authors: Bassi Nicola , Hovland Henrikke Nilsen , Rasheed Kashif , Jarhelle Elisabeth , Pedersen Nikara , Mchaina Eunice Kabanyana , Bakkan Sara Marie Engelsvold , Iversen Nina , Høberg-Vetti Hildegunn , Haukanes Bjørn Ivar , Knappskog Per Morten , Aukrust Ingvild , Ognedal Elisabet , Van Ghelue Marijke
Published: April 2023

Background

Damaging alterations in theBRCA1gene have been extensively described as one of the main causes of hereditary breast and ovarian cancer (HBOC).BRCA1alterations can lead to impaired homologous recombination repair (HRR) of double-stranded DNA breaks, a process which involves the RING, BRCT and coiled-coil domains of the BRCA1 protein. In addition, the BRCA1 protein is involved in transcriptional activation (TA) of several genes through its C-terminal BRCT domain.

Methods

In this study, we have investigated the effect on HRR and TA of 11 rareBRCA1missense variants classified as variants of uncertain clinical significance (VUS), located within or in close proximity to the BRCT domain, with the aim of generating additional knowledge to guide the correct classification of these variants. The variants were selected from our previous study “BRCA1Norway”, which is a collection of allBRCA1variants detected at the four medical genetic departments in Norway.

Results

All variants, except one, showed a significantly reduced HRR activity compared to the wild type (WT) protein. Two of the variants (p.Ala1708Val and p.Trp1718Ser) also exhibited low TA activity similar to the pathogenic controls. The variant p.Trp1718Ser could be reclassified to likely pathogenic. However, for ten of the variants, the total strength of pathogenic evidence was not sufficient for reclassification according to the CanVIG-UKBRCA1/BRCA2gene-specific guidelines for variant interpretation.

Conclusions

When including the newly achieved functional evidence with other available information, one VUS was reclassified to likely pathogenic. Eight of the investigated variants affected only one of the assessed activities of BRCA1, highlighting the importance of comparing results obtained from several functional assays to better understand the consequences ofBRCA1variants on protein function. This is especially important for multifunctional proteins such as BRCA1.
AC010883.5 promotes cell proliferation, invasion, migration, and epithelial-to-mesenchymal transition in cervical cancer by modulating the MAPK signaling pathway
Authors: Gan Qiyu , Huang Xia , Zhao Wenrong , Liu Hui , Xu Yan , Zhang Xiaohua , Cheng Jingxin , Chen Rui
Published: April 2023

Homo sapiens chromosome 2 clone RP11-339H12 (AC010883.5) is a dysregulated long non-coding RNA (lncRNA) that has never been investigated in cervical cancer (CC). Thus, the potential function and molecular mechanism remain unclear. Our study explored the biological function of AC010883.5 to determine the underlying mechanisms in CC and provide potential therapeutic targets for improving the clinical treatment strategy. We used quantitative real-time polymerase chain reaction to measure mitochondrial RNA levels and western blot to measure the protein levels of target genes. Further, we used Cell Counting Kit-8 and 5‐Bromo-2'-deoxyuridine incorporation assays to evaluate cell proliferation in vitro. Cell apoptosis was analyzed by flow cytometry. Cell invasion was analyzed by wound healing and Transwell migration assays was ued to analyze cell migration. Finally, the biological function and mechanism of AC010883.5 in CC growth were evaluated by in vivo xenograft assay. AC010883.5 was enhanced in CC tissues and cell lines, and enhanced AC010883.5 expression accelerated CC cell proliferation, migration, and invasion and induced epithelial–mesenchymal transition in vitro and in vivo. AC010883.5 also activated the mitogen-activated protein kinase (MAPK) signaling pathway by promoting phosphorylation of extracellular signal-regulated kinase 1/2 (i.e., ERK1/2) and MAPK kinase 1/2 (i.e., MEK1/2). Blocking the MAPK signaling pathway could counteract the pro-proliferative, pro-migrative, and pro-invasive effects of AC010883.5 over-expression. We found that the lncRNA, AC010883.5, is an oncogenic molecule involved in CC tumor progression via dysregulation of the MAPK signaling pathway, implying that AC010883.5 could be a tumor progression and therapeutic response biomarker.
Abnormal functional connectivity of the nucleus accumbens subregions mediates the association between anhedonia and major depressive disorder
Authors: Hu Yanqin , Zhao Chaoqi , Zhao Houfeng , Qiao Juan
Published: April 2023

Background

The nucleus accumbens (Nac) is a crucial brain region in the pathophysiology of major depressive disorder (MDD) patients with anhedonia. However, the relationship between the functional imaging characteristics of Nac subregions and anhedonia remains unclear. Thus, this study aimed to investigate the role of resting-state functional connectivity (rsFC) of the Nac subregions between MDD and anhedonia.

Methods

We performed resting-state functional magnetic resonance imaging (fMRI) to measure the rsFC of Nac subregions in 55 MDD patients and 30 healthy controls (HCs). A two-sample t test was performed to determine the brain regions with varying rsFC among Nac subregions between groups. Then, correlation analyses were carried out to investigate the relationships between the aberrant rsFC of Nac subregions and the severity of anhedonia. Furthermore, we constructed a mediation model to explain the role of the aberrant rsFC of Nac subregions between MDD and the severity of anhedonia.

Results

Compared with the HC group, decreased rsFC of Nac subregions with regions of the prefrontal cortex, insula, lingual gyrus, and visual association cortex was observed in MDD patients. In the MDD group, the rsFC of the right Nac shell-like subregions with the middle frontal gyrus (MFG)/superior frontal gyrus (SFG) was correlated with consummatory anhedonia, and the rsFC of the Nac core-like subdivisions with the inferior frontal gyrus (IFG)/insula and lingual gyrus/visual association cortex was correlated with anticipatory anhedonia. More importantly, the functional alterations in the Nac subregions mediated the association between anhedonia and depression.

Conclusions

The present findings suggest that the functional alteration of the Nac subregions mediates the association between MDD and anhedonia, which provides evidence for the hypothesis that MDD patients have neurobiological underpinnings of reward systems that differ from those of HCs.
The effect of mindfulness-based stress reduction on rejection sensitivity and resilience in patients with thalassemia: a randomized controlled trial
Authors: Ghonchehpour Asma , Forouzi Mansooreh Azizzadeh , Dehghan Mahlagha , Ahmadi Atefeh , Okou Gloria , Tirgari Batool
Published: April 2023

Background

Thalassemia is a genetic and chronic congenital disorder composed of physical problems that severely impair patients’ cognitive, psychological and social processes. The rehabilitation of patients is particularly important because they have a high rejection sensitivity and low resilience. The present study aimed to determine the effects of mindfulness-based stress reduction counseling on rejection sensitivity and resilience in patients with thalassemia referring to a dedicated disease center in Kerman, Iran.

Materials and methods

We conducted this randomized controlled trial study on 66 patients with thalassemia referring to the Kerman Thalassemia Center in Kerman, Iran in 2022. Using convenience sampling and the stratified block randomization method, we divided the samples into two intervention (N = 33) and control (N = 33) groups. Patients in the intervention group received eight 60-min online mindfulness-based stress reduction counseling sessions (one session per week) and completed the Rejection Sensitivity Questionnaire, Adult Version (A-RSQ) and the Conner-Davidson Resilience Scale before and after the intervention. We collected data using the SPSS 25 trial and descriptive statistics (frequency, percentage, mean and standard deviation), Chi-Square test, Independent-samples t-test, Fisher's exact test, and Analysis of covariance. A significance level of 0.05 was considered.

Results

We found no significant difference in the mean scores of rejection sensitivity between the intervention (8.75 ± 4.86) and control groups (9.87 ± 5.16) before the intervention. Mean scores for rejection sensitivity were 10.23 ± 4.94 in the control group and 7.11 ± 4.13 in the intervention group after the intervention, the results of analysis of covariance showed that, there was a significant difference between two groups after the intervention (F = 7.52, p = 0.008). The mean resilience score in the control group was 63.69 ± 19.43, while it was 67.72 ± 17.98 in the intervention group before the intervention and there is no significant difference between them, but the mean resilience scores in the control and intervention groups were 58.06 ± 22.81 and 74.18 ± 17.46 after the intervention, respectively. the results of analysis of covariance showed that, there was a significant difference between two groups after the intervention (F = 9.28, p = 0.004).

Conclusion

Our results showed that in addition to other physical treatments, mindfulness-based stress reduction counseling was effective in reducing the patient’s rejection sensitivity and increasing the resilience of patients with thalassemia.
The Culture is Prevention Project: measuring cultural connectedness and providing evidence that culture is a social determinant of health for Native Americans
Authors: Masotti Paul , Dennem John , Bañuelos Karina , Seneca Cheyenne , Valerio-Leonce Gloryanna , Inong Christina Tlatilpa , King Janet
Published: April 2023

Background

It is important for non-Native persons to understand that the meaning of culture to Native American/Indigenous Peoples is not about esteem, taste or music but rather is described as a cognitive map on how to be. Native American/Indigenous culture can be thought of as all the things and ways in which Native/Indigenous people understand who they are, where they come from and how they are to interact with others. Hundreds of years across many generations have taught that culture-based activities and interventions improve Native/Indigenous health and wellbeing. We explore if increased Native American culture/cultural connectedness is associated with better mental health/well-being and physical health.

Methods

We analyzed data from a two-phased study (N = 259 and N = 102) of 361 urban Native Americans in California (2018–2021). The 29 items validated Cultural Connectedness Scale-California (CCS-CA) measured Native culture/cultural connectedness. Mental health/well-being and physical health were assessed using the: modified Herth Hope Index (mHHI), Satisfaction with Life (SWL), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R-10), Substance Abuse (CAGE-AID), and Health Related Quality of Life (HRQOL). We conducted Pearson correlations and stepwise regression analyses with CCS-CA as the independent (predictor) variable to explore our main research questions: 1) Is increased Native American/Indigenous culture associated with: 1) better mental health/well-being; and 2) better physical health?

Results

Increased Native/Indigenous culture (CCS-CA scores) is significantly associated with better mental health/well-being (mHHI, p < .001) and satisfaction with life (SWL, p < .001) predicts good physical health days (HRQOL, p < .001). Increased connection to Native American/Indigenous culture (CCS-CA scores) is significantly associated with decreased risk for depression (CESD-R-10, p < .0) and substance abuse and (CAGE-AID, p < .07). Significant results for culture as protective against risk for substance abuse (CAGE-AID) was most likely affected (p value approaching significance) due to an error in language on the measure (i.e., created double negative).

Conclusions

Native American/Indigenous culture is a predictor of improved outcomes for mental health/well-being and physical healthy days. Native culture is an important social determinant of health. We add to the evidence that Native/Indigenous culture (i.e., cultural connectedness) be considered an important intervention objective and health-related outcome measure.
Development and validation of a risk score for predicting inconsistent condom use with women among men who have sex with men and women
Authors: Chen Lin , Jiang Tingting , Wang Hui , Hong Hang , Ge Rui , Tang Huiling , Wang Shanling , Xu Ke , Chai Chengliang , Ma Qiaoqin , Jiang Jianmin
Published: April 2023

Background

Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized.

Methods

This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately.

Results

Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p < 0.05). Four risky predictors of ICUF were identified: Duration of local residence ≦6 months; more than one male partner in the prior 6 months; inconsistent condom use with males in the prior 6 months; and never heard post-exposure prophylaxis (PEP). The proportions of respondents indicating ICUF in the low- (0), medium- (2–4) and high-risk (6–20) groups (according to our risk scoring system) were 11.7% (14/120), 26.9% (96/357), and 78.1% (125/160), respectively (Ptrend < 0.001). In the validation survey, the respective proportions of those reporting ICUF were 13.4% (15/112), 17.8% (24/185) and 87.3% (96/110) (Ptrend < 0.001).

Conclusions

We developed and validated a predictive risk score for ICUF among MSMW; four factors were identified, of which inconsistent condom use with men was the most important. Risk reduction intervention programs should focus on MSM who report inconsistent condom use with males, never heard PEP, having multiple partners and living in local less than 6 months.
Smokers’ strategies to reduce tobacco spending: self-reported use and differences across subgroups. Findings from the International Tobacco Control (ITC) Netherlands Survey
Authors: Geboers Cloé , Candel Math J. J. M. , Nagelhout Gera E. , de Vries Hein , van den Putte Bas , Fong Geoffrey T. , Willemsen Marc C.
Published: April 2023

Background

The cost of tobacco is one of the most reported reasons for smoking cessation. Rather than quitting, smokers can use also strategies to reduce tobacco expenditure while continuing smoking, such as smoking less or using price-minimising strategies. The Netherlands announced to increase the price of a pack cigarettes from seven (2018) to ten euros (2023), to reduce tobacco prevalence and consumption. This study explores the self-reported strategies to reduce tobacco spending among Dutch smokers, and whether this differed per age, income, and education. Additionally, we analysed among quitters in these subgroups whether price played a role in their decision to quit.

Methods

Cross-sectional survey data from the International Tobacco Control (ITC) Netherlands Wave 2 (September–November 2020,N = 1915) was used. Strategies to reduce spending among smokers (N = 1790) were: reducing consumption, bulk buying, switching to cheaper products or buying from low-taxed sources. These were collapsed into: reducing consumption (solely or in combination with other behaviours), solely price-minimising behaviours (such as buying cheaper brands), or no strategies to reduce spending. Associations between strategies and characteristics were analysed through multinomial and binary logistic regression models. Second, we explored which subgroups were more likely to report that price played a role in their decision to quit among quitters (N = 125).

Results

The majority of smokers used strategies to reduce tobacco spending: 35.6% reduced consumption and 19.3% used solely price-minimising strategies. 82.1% of quitters reported that price played a role in their decision to quit. Low-income individuals were more likely to report price as a reason for quitting and reduce consumption, but also to buy cheaper products. Highly nicotine dependent smokers were more likely to use price-minimising behaviours, and less likely to reduce consumption.

Conclusions

The majority reported using strategies to reduce spending or that price played a role in their decision to quit. Reducing consumption was the most reported strategy. Low-income smokers were more likely to reportedly reduce consumption, buy cheaper products, or quit. Price policies have the potential to reduce socioeconomic inequalities in smoking. To discourage price-minimising behaviours, such as switching to cheaper products, reducing price differences between products should be prioritized.
Evaluation of surgical outcomes and prognostic factors of second primary lung cancer based on a systematic review and meta-analysis
Authors: Zhao Jie , Shen Zhenghai , Huang Yunchao , Zhao Guangqiang , Wang Wei , Yang Yantao , Zhou Chen , Ye Lianhua
Published: April 2023

Background

Although surgery has been widely applied for SPLC therapy, there is still no uniform treatment approach. Whether SPLC and primary lung cancer have similar prognostic characteristics remains controversial. Herein, based on a systematic review and meta-analysis, we aimed to enucleate the influences of diverse surgical strategies and underlying prognostic factors on the prognosis of patients with both the first primary lung cancer and SPLC underwent surgical resection.

Methods

A comprehensive and systematic literature search was implemented in three databases (MEDLINE, EMBASE, and Cochrane), and eligible studies were screened following inclusion and exclusion criteria. Meanwhile, we extracted the hazard ratios (HR) together with 95% confidence intervals (CI) for each prognostic factor, either directly or indirectly, from the enrolled literature.

Results

Eleven studies (published between 2000 and 2022) were included in this study, including 1,131 SPLC patients. The overall survival (OS) exhibited no difference between patients with lobectomy and sublobar resection after SPLC (HR: 0.87, 95%CI: 0.62–1.21, P = 0.41). The patients after completion pneumonectomy had a poor prognosis (HR: 1.85, 95% CI: 1.34–2.55, P < 0.01). Poor prognostic factors after SPLC surgery included synchronous SPLC (HR: 3.38, 95%CI: 1.53–7.46, P < 0.01), tumor diameter > 2 cm (HR: 2.44, 95%CI: 1.73–3.44, P < 0.01), solid predominant in CT morphology (HR: 3.08, 95% CI: 1.14–8.33, P = 0.03), lymph node metastasis (HR: 2.79, 95%CI: 1.40–5.56), and smoking (HR: 2.37, 95%CI: 1.08–26.82, P < 0.01). Tumor disease-free interval (DFI), tumor histological type, and gender had no impact on the prognosis of patients received SPLC surgery.

Conclusions

Patients with SPLC, especially those with poor cardiopulmonary function reserve, should be prioritized for sublobar resection for treatment. These patients should also try to avoid completion pneumonectomy. Patients with synchronous SPLC, tumor diameter > 2 cm, solid predominant in CT morphology, lymph node metastasis, and smoking had a poor prognosis. Meanwhile, SPLC has similar prognostic characteristics with single primary lung cancer. However, the study has some limitations and more evidence is warranted to verify the findings.
Quality of life in patients with primary hyperparathyroidism before and after parathyroidectomy: long term single center experience
Authors: Ionova T. I. , Buzanakov D. M. , Chernikov R. A. , Efremov S. M. , Gladkova I. N. , Nikitina T. P. , Sleptsov I. V. , Zolotoukho A. V. , Bubnov K. A. , Skvortsov V. V. , Vinogradova A. A. , Rusakov V. F.
Published: April 2023

Background

Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by a parathyroid tumor or hyperplasia, which is often accompanied with quality of life (QoL) impairment. A parathyroidectomy (PTX) is the preferred standard treatment for PHPT patients. In this single center study we aimed to evaluate the impact of PHPT on patient’s QoL and identify QoL changes at early and long-term follow-up after surgery.

Methods

All the patients underwent routine PTX with the removal of the suspected hyperparathyroid gland(s). Patients filled out generic QoL questionnaire RAND SF-36, specific questionnaire PHPQoL and specific symptom assessment questionnaire PAS upon admission to the hospital before surgery, at 3 months, 12 months and 24 months after surgery.

Results

A total of 92 patients with PHPT (median age was 56 years, 95.7% females) were included in the study. Before PTX patient’s QoL by SF-36 scores was significantly lower as compared to healthy controls (p < 0.01). Almost 40% of patients had poor or very poor QoL. The most frequent symptoms by PAS before surgery were as follows: tiredness (97.8% of patients), weakness (94.6%), forgetfulness (94.6%), mood changes (90%), feeling “blue”/depression (88%), joint pains (83.3%), headaches (80.2%), constant irritability (77.2%), bone pains (75%), thirst (70.7%) and trouble getting out of a chair (67.4%). The half of the patients had moderate-to-severe (≥ 40 scores) tiredness, weakness, joint pains, forgetfulness, as well as mood changes. Post-operative QoL changes were analysed in the group of 72 patients. After surgery there was significant improvement in QoL by all scales of SF-36 questionnaire, excluding bodily pain, and the PHPQoL total score (GEE, p < 0.01) as compared with their values before surgery. Also severity of tiredness, mood changes, weakness and forgetfulness significantly decreased after surgery as compared to their baseline values (GEE, p < 0.05). Decreased mental component of QoL by PHPQoL (OR = 0.927, 95%CI = 0.874–0.984, p = 0.013) predicted improved QoL after surgery.

Conclusions

Patients with PHPT demonstrated significantly impaired QoL in physical, psychological and social functioning as well experienced a wide profile of common PHPT symptoms. Successful PTX was accompanied with remarkable QoL improvement and decrease in subjective symptoms for at least 24 months after surgery.
How do former medical and nursing undergraduates describe their learning on an interprofessional training Ward 12–18 months later? – A retrospective qualitative analysis
Authors: Mink Johanna , Zurek Bianka , Götsch Burkhard , Mihaljevic André L. , Mitzkat Anika , Trierweiler-Hauke Birgit , Mahler Cornelia
Published: April 2023

Background

Interprofessional training wards (IPTWs) seem to deliver good results in terms of development of interprofessional competencies. However, evidence of long-term effects of these training wards on learners’ competency development is lacking and little is known about retrospective evaluation of IPTWs. Therefore, this study aimed to explore the retrospective evaluation of competency development and interprofessional collaboration of former undergraduates 12 or more months after a placement on an IPTW.

Methods

Eight follow-up interviews were conducted with four nursing and four medical professionals 12–18 months after they had finished a placement on an ITPW throughout their vocational training. Interviews were translated verbatim and analysed deductively and inductively based on qualitative content analysis.

Results

The qualitative content analyses deductively identified two main categories regarding the research question, namely the uniqueness of the programme and interprofessional competencies developed by the Interprofessional Education Collaborative. Sub categories were identified inductively, representing the perceived competency development and the learning opportunities on the IPTW as compared to other clinical placements throughout vocational training and in transition to practice. Interviewees seemed to have developed competencies that are important for interprofessional collaboration such as communication, roles and responsibilities, as well as competencies in patient care and management. Considered beneficial for learning were the opportunity to work self-responsibly and the interprofessional collaboration on the IPTW, both of which were neither possible in almost any other placement nor in transition to practice.

Conclusion

Findings show that IPTWs can be sufficient in competency development and role clarification and are perceived positively by learners, but structures in clinical practice can impede sustaining competency development and efficient interprofessional collaboration.
Students engagement using polls in virtual sessions of physiology, pathology, and pharmacology at King Saud bin Abdulaziz University for Health Sciences during COVID-19 pandemic: a cross-sectional study
Authors: Bawazeer Mona Abubakr , Aamir Saima , Othman Fatmah , Alkahtani Reem
Published: April 2023

Background

Active involvement of students in class using technology is associated with effective learning and understanding. This work intended to analyze the impact of interactive teaching on medical students’ engagement, learning, performance, understanding and attendance in virtual classes of physiology, pathology, and pharmacology during COVID-19 pandemic.

Methods

A descriptive cross-sectional study was carried out at college of medicine at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) in Riyadh during January-April 2022. Third- and fourth-year medical students filled a self-reported questionnaire that assessed students’ engagement, understanding, performance, and attendance during the sessions of three courses within the curriculum. The Chi-square test or Fisher’s exact test was used to compare the difference between the survey responses.

Results

A total of 184/234 questionnaires were completed and returned, with an overall response rate of 78.6%. Fifty-five percent of the participants were involved at least more than 5 times in polls during the class. Majority (86.9%), of the students agreed on enjoying participation in polls during the class, and 88.9% recommended the utilization of the polls again. Participation in polls improved understanding and performance of 88%, and 63% of students respectively. In addition, 38% were neutral regarding attendance improvement and spending more time for the class. Around 53% students agreed that polls improved their grades.

Conclusion

In conclusion, this study showed that there is an impact of using interactive polls in virtual classes in medical students at KSAU-HS. It is recommended to continue using polls in all subjects in on-site sessions. This will be a great preface step toward switching the traditional teaching to the interactive teaching using flipped classroom strategy in the future.
The fudan tinnitus relieving system application for tinnitus management
Authors: Tang Dongmei , Wang Haiyan , Gu Dantong , Ye Lei , Sun Shan , Li Huawei
Published: April 2023

Objective

Tinnitus is a highly prevalent hearing disorder, and the burden of tinnitus diagnosis and treatment is very heavy, especially in China. In order to better benefit the majority of tinnitus patients, we developed a new mobile app based on our patented invention – named the Fudan Tinnitus Relieving System (FTRS) – for tinnitus management. The FTRS app aims to alleviate patients’ tinnitus symptoms using customized sound therapy, to evaluate the treatment effect, to provide a doctor-patient communication platform, and to support tinnitus rehabilitation and auditory health.

Methods

In this study, we introduced the major functions of the FTRS app, analyzed the geographical distribution of users around China, and performed an analysis on the demographic and clinical characteristics of patients with tinnitus, including age and tinnitus position, duration, frequency, and severity in both men and women based on the user information collected by the FTRS. The data for 22,867 participants (males: 13,715; females: 9,152) were included in the statistical analysis.

Results

The FTRS app has been popular with tinnitus patients since its launch in May 2018 with its integrated pitch-matching test, individualized sound therapy, follow-up assessment, and provision of easy-to-understand science and education for tinnitus. The users were located throughout Mainland China but primarily concentrated in Shanghai, Jiangsu, Zhejiang, Guangdong, and Shandong provinces. We observed gender differences regarding age and tinnitus frequency, severity, and position among the app’s users. The FTRS has not only facilitated patients’ access to treatment at times and places that are convenient for them, but also provides a large amount of data based on user feedback in order to support clinical tinnitus research.

Conclusions

Compared with traditional face-to-face medical treatment, the FTRS greatly reduced medical costs and enabled patients with tinnitus to arrange their own treatment times. At the same time, the FTRS has provided standardized tinnitus data that have laid a foundation for clinical research on tinnitus. However, because of differences in the popularity and utilization of smart devices, FTRS user data might only reflect the situation of tinnitus patients who can effectively use smart devices. Therefore, the findings of this study need to be interpreted with caution.
Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting
Authors: Soilly AL , Robert-Viard C , Besse C , Bruel AL , Gerard B , Boland A , Piton A , Duffourd Y , Muller J , Poë C , Jouan T , El Doueiri S , Faivre L , Bacq-Daian D , Isidor B , Genevieve D , Odent S , Philip N , Doco-Fenzy M , Lacombe D , Asensio ML , Deleuze JF , Binquet C ,   DISSEQ Investigators Group, Arpin S , Blanchet P , Blesson S , Boute-Benejean O , Busa T , Colin E , Coubes C , Devillard F , Edery P , El Chehadeh S , Fradin M , Goldenberg A , Guerrot A-M , Herenger Y , Houcinat N , Jean-Marcais N , Jouk P. S. , Lambert L , Lavillaureix A , Legendre M , Leheup B , Manouvrier S , Mercier S , Moutton S , Nizon M , Pasquier L , Petit F , Pinson L , Poirsier C , Pons L , Putoux A , Quelin C , Renaud M , Rossi M , Sorlin A , Spodenkiewicz M , Thevenon J , Toutain A , Van-Gils J , Vanlerberghe C , Verloes A , Vincent M , Vincent-Delorme C , Willems M , Ziegler A , Thauvin-Robinet C , Lejeune C
Published: April 2023

Background

With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers.

Methods

A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed.

Results

The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID.

Conclusion

This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES.

Trial registration

ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.
Scrutinizing human resources for health availability and distribution in Mozambique between 2016 and 2020: a subnational descriptive longitudinal study
Authors: Fernandes Quinhas , Augusto Orvalho , Machai Helena , Pfeiffer James , Carone Marco , Pinto Norton , Carimo Naziat , Ramiro Isaías , Gloyd Stephen , Sherr Kenneth
Published: April 2023

Introduction

Overall, resilient health systems build upon sufficient, qualified, well-distributed, and motivated health workers; however, this precious resource is limited in numbers to meet people’s demands, particularly in LMICs. Understanding the subnational distribution of health workers from different lens is critical to ensure quality healthcare and improving health outcomes.

Methods

Using data from Health Personnel Information System, facility-level Service Availability and Readiness Assessment, and other sources, we performed a district-level longitudinal analysis to assess health workforce density and the ratio of male to female health workers between January 2016 and June 2020 across all districts in Mozambique.

Results

22 011 health workers were sampled, of whom 10 405 (47.3%) were male. The average age was 35 years (SD: 9.4). Physicians (1025, 4.7%), maternal and child health nurses (4808, 21.8%), and nurses (6402, 29.1%) represented about 55% of the sample. In January 2016, the average district-level workforce density was 75.8 per 100 000 population (95% CI 65.9, 87.1), and was increasing at an annual rate of 8.0% (95% CI 6.00, 9.00) through January 2018. The annual growth rate declined to 3.0% (95% CI 2.00, 4.00) after January 2018. Two provinces, Maputo City and Maputo Province, with 268.3 (95% CI 186.10, 387.00) and 104.6 (95% CI 84.20, 130.00) health workers per 100 000 population, respectively, had the highest workforce density at baseline (2016). There were 3122 community health workers (CHW), of whom 72.8% were male, in January 2016. The average number of CHWs per 10 000 population was 1.33 (95% CI 1.11, 1.59) in 2016 and increased by 18% annually between January 2016 and January 2018. This trend reduced to 11% (95% CI 0.00, 13.00) after January 2018. The sex ratio was twice as high for all provinces in the central and northern regions relative to Maputo Province. Maputo City (OR: 0.34; 95% CI 0.32, 0.34) and Maputo Province (OR: 0.56; 95% CI 0.49, 0.65) reported the lowest sex ratio at the baseline. Encouragingly, important sex ratio improvements were observed after January 2018, particularly in the northern and central regions.

Conclusion

Mozambique made substantial progress in health workers’ availability during the study period; however, with a critical slowdown after 2018. Despite the progress, meaningful shortages and distribution disparities persist.
Analogies between the periphery of cancer and the leading edge of pulmonary fibrosis
Authors: Pernia Marin Monica , Salvatore Mary
Published: April 2023

The periphery of malignant tumors and the leading edge of fibrotic tissue have analogous metabolic pathways. Both use glycolysis as the primary source of energy to produce biomass with consequential acidification of the microenvironment. A low PH has been shown to increase the ability of cancer cells to invade the surrounding tissue in both in vitro and in vivo studies. The pH-dependent activation of TGF-B leading to myofibroblast activation is an important step in the initiation and progression of fibrosis. Markers of accelerated cell proliferation have also been reported in the periphery of malignant tumors and the leading edge of fibrosis. Understanding the shared molecular and metabolic characteristics of these conditions may explain the increased prevalence of cancer among patients with fibrosis.