bluuebunny/crossref_metadata_2025 huggingface dataset:
The conundrums of the reasonable patient standard in English medical law
Authors: Kwok Kelvin Hiu Fai , Ip Eric C. , Lee Shing Fung
Published: February 2023

Background

In its 2015 decision in Montgomery v. Lanarkshire Health Board, the Supreme Court of the United Kingdom overruled the long-standing, paternalistic prudent doctor standard of care in favour of a new reasonable patient standard which obligates doctors to make their patients aware of all material risks of the recommended treatment and of any reasonable alternative treatment. This landmark judgment has been of interest to the rest of the common law world. A judicial trend of invoking Montgomery to impose more stringent requirements on doctors is discernible in subsequent decisions since then.

Main body

In this narrative review, without questioning the idea that properly informed patients should play a more active role in procedures affecting their own health in furtherance of their autonomy, safety, and consumer rights, we identify and analyse, with the aid of realistic clinical thought experiments, three practical conundrums that the Montgomery standard may inflict on the daily work of doctors, unfairly exposing them to arbitrary legal risks.

Conclusions

These conundrums pertain to the ascertainment of the risks that must be disclosed to the patient under the test of ‘materiality’; the legal uncertainty as to the scope of the exceptions; and the actual ability of doctors to cope with the pressures of time. These conundrums offer ripe opportunities to rethink the proper role of judicially developed medical law in modern health care practice.
Patients acceptance and comprehension to written and verbal consent (PAC–VC)
Authors: Kashur Rabia , Ezekowitz Justin , Kimber Shane , Welsh Robert C.
Published: February 2023

Background

Acute myocardial infarction (AMI) research is challenging as it requires enrollment of acutely ill patients. Patients are generally in a suboptimal state for providing informed consent. Patients’ understanding to verbal assents have not been previously examined in AMI research. Patients Acceptance and Comprehension to Written and Verbal Consent (PAC–VC) compared patients’ understanding and attitudes to verbal and written consents in AMI RCTs.

Methods

PAC–VC recruited patients from 3 AMI trials using both verbal N = 12 and written N = 6 consents. We compared patients’ understanding using two survey questionnaires. The first questionnaire used open-ended questions with multiple choice answers. The second questionnaire used a 5-point Likert scale to measure patients understanding and attitudes to the consent process. Overall answers average scores were categorized into three groups: Adequate understanding (71–100) %, Partial understanding (41–70)% and Inadequate understanding (0–40)%.

Results

Responses showed patients with verbal assent had adequate understanding to most components of informed consent, close to those of written consent. Most patients did not read written information entirely and believed that it is not important to make a final decision. Patients favoured to have written information be part of the consent but not necessarily presented during the initial consent process. Patients felt less pressured in the verbal assent arm than those of written consent.

Conclusion

Patients had adequate understanding to most components of verbal assent and comparable to those of written consent. Utilizing verbal assents in the acute care setting should be further assessed in larger trials.
Dignity at stake – relatives’ experiences of influencing dignified care in nursing homes
Authors: Hartviksen Trude Anita , Aspfors Jessica , Uhrenfeldt Lisbeth
Published: February 2023

Background

Dignity, in the care of older nursing home residents, has been an increasingly part of the public discourse the recent years. Despite a growing body of knowledge about dignity and indignity in nursing homes, we have less knowledge of how relatives experience their role in this context. This study is a follow-up to a previous study in nursing homes, which gave rise to concern about the relatives’ descriptions of residents’ dignity. The aim of this current study is to critically discuss relatives’ experiences of influencing the dignified care of residents of nursing homes.

Methods

Methodologically, the study is informed by a critical hermeneutic stance, where the analysis is guided by a qualitative interpretive approach and a humanizing framework. This is a secondary analysis that includes data from five semi-structured focus groups from a previous study. The participants were 18 relatives of 16 residents living in two nursing homes in rural northern Norway.

Results

The main theme in this study, preventing missed care when dignity is at stake, is identified when relatives of nursing homes experience that they are able to influence dignified care by (a) pinpointing to prevent missed care and (b) compensating when dignity is threatened.

Conclusions

Despite their stated good intentions to safeguard dignity, relatives of nursing homes experience being alienated in their attempts to change what they describe as undignified and unacceptable practice into dignified care. The relatives’ observations of dignity and indignity are, contrary to what national and international regulations require, not mapped and/or used in any form of systematic quality improvement work. This indicates that knowledge-based practice in nursing homes, including the active application of user and relative knowledge, has untapped potential to contribute to quality improvement towards dignified care.
Krüppel-like factor 9 (KLF9) links hormone dysregulation and circadian disruption to breast cancer pathogenesis
Authors: Ybañez Weand S. , Bagamasbad Pia D.
Published: February 2023

Background

Circadian disruption is an emerging driver of breast cancer (BCa), with epidemiological studies linking shift work and chronic jet lag to increased BCa risk. Indeed, several clock genes participate in the gating of mitotic entry, regulation of DNA damage response, and epithelial-to-mesenchymal transition, thus impacting BCa etiology. Dysregulated estrogen (17β-estradiol, E2) and glucocorticoid (GC) signaling prevalent in BCa may further contribute to clock desynchrony by directly regulating the expression and cycling dynamics of genes comprising the local breast oscillator. In this study, we investigated the tumor suppressor gene, Krüppel-like factor 9 (KLF9), as an important point of crosstalk between hormone signaling and the circadian molecular network, and further examine its functional role in BCa.

Methods

Through meta-analysis of publicly available RNA- and ChIP-sequencing datasets from BCa tumor samples and cell lines, and gene expression analysis by RT-qPCR and enhancer- reporter assays, we elucidated the molecular mechanism behind the clock and hormone regulation of KLF9. Lentiviral knockdown and overexpression of KLF9 in three distinct breast epithelial cell lines (MCF10A, MCF7 and MDA-MB-231) was generated to demonstrate the role of KLF9 in orthogonal assays on breast epithelial survival, proliferation, apoptosis, and migration.

Results

We determined that KLF9 is a direct GC receptor target in mammary epithelial cells, and that induction is likely mediated through coordinate transcriptional activation from multiple GC-responsive enhancers in the KLF9 locus. More interestingly, rhythmic expression of KLF9 in MCF10A cells was abolished in the highly aggressive MDA-MB-231 line. In turn, forced expression of KLF9 altered the baseline and GC/E2-responsive expression of several clock genes, indicating that KLF9 may function as a regulator of the core clock machinery. Characterization of the role of KLF9 using complementary cancer hallmark assays in the context of the hormone-circadian axis revealed that KLF9 plays a tumor-suppressive role in BCa regardless of molecular subtype. KLF9 potentiated the anti-tumorigenic effects of GC in E2 receptor + luminal MCF7 cells, while it restrained GC-enhanced oncogenicity in triple-negative MCF10A and MDA-MB-231 cells.

Conclusions

Taken together, our findings support that dysregulation of KLF9 expression and oscillation in BCa impinges on circadian network dynamics, thus ultimately affecting the BCa oncogenic landscape.
Public health determinants of child malaria mortality: a surveillance study within Siaya County, Western Kenya
Authors: Hollowell Thomas , Sewe Maquins Odhiambo , Rocklöv Joacim , Obor David , Odhiambo Frank , Ahlm Clas
Published: February 2023

Background

Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region.

Methods

A total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research Institute/Center for Disease Control Health and Demographic Surveillance System (KEMRI/CDC HDSS) study area in Siaya County during the period 2003–2013. Cause of death was determined by use of verbal autopsy.

Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined.

Results

In total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIV/AIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10–7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29–1.60), l ow maternal education HR 3.91 (95% CI 1.86–8.22), and low socioeconomic status HR 1.44 (95% CI 1.26–1.64) were all significantly associated with increased hazard of malaria death among children.

Conclusions

While child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions.
SARS-CoV-2 antibody prevalence, correlates, and access to harm reduction services among people who inject drugs living with and without HIV and their partners in Kenya
Authors: Doshi Shradha , Kingston Hanley , Tseng Ashley S. , Chohan Bhavna H. , Sambai Betsy , Guthrie Brandon L. , Monroe-Wise Aliza , Mbogo Loice W. , Masyuko Sarah , Tram Khai Hoan , Sinkele William , Macharia Paul , Bukusi David , Herbeck Joshua T. , Farquhar Carey
Published: February 2023

Background

In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic.

Methods

This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting and/or sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence.

Results

One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range: 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] 0.51, 0.95; p < 0.01) Participants who reported a sexual or injecting partner diagnosed with SARS-CoV-2 were twofold more likely to have SARS-CoV-2 antibodies detected (aOR = 2.21, 95% CI 1.06, 4.58; p < 0.032). Living with HIV was not associated with presence of SARS-CoV-2 antibodies.

Conclusion

The seroprevalence of SARS-CoV-2 of 30.9% in this cohort suggests high transmission rates within this population. SARS-CoV-2 seroprevalence was similar for people living with and without HIV. A large portion of this population was noted to have had disruption in access to harm reduction services.
Identification of critical prognosis signature associated with lymph node metastasis of stomach adenocarcinomas
Authors: Wang Xiaohui , Zhang Wei , Guo Yulin , Zhang Yifei , Bai Xiaofeng , Xie Yibin
Published: February 2023

Lymph node metastasis (LNM) is an important factor affecting the prognosis of patients with gastric adenocarcinoma (STAD), which is the most common malignancy of the human digestive system. Current detection techniques have limited sensitivity and specificity, and there is a lack of effective biomarkers to screen for LNM. Therefore, it is critical to screen for biomarkers that predict LNM in STAD. Gene expression differential analysis (false discovery rate < 0.05, |log2Fold change| ≥1.5) was performed on 102 LNM samples, 224 non-LNM samples, and 29 normal gastric tissue samples from The Cancer Genome Atlas (TCGA) STAD dataset, and 269 LNM-specific genes (DEGs) were obtained. Enrichment analysis showed that LNM-specific genes functioned mainly in cytokine-cytokine receptor interactions, calcium signaling, and other pathways. Ten DEGs significantly associated with overall survival in STAD patients were screened by multivariate Cox regression, and an LNM-based 10-mRNA prognostic signature was established (Logrank P < 0.0001). This 10-mRNA signature was well predicted in both the TCGA training set and the Gene Expression Omnibus validation dataset (GSE84437) and was associated with survival in patients with LNM or advanced-stage STAD. Using Kaplan-Meier survival, receiver operating characteristic curve, C-index analysis, and decision curve analysis, the 10-mRNA signature was found to be a more effective predictor of prognosis in STAD patients than the other two reported models (P < 0.0005). Protein-protein interaction network and gene set enrichment analysis of the 10-mRNA signature revealed that the signature may affect the expression of multiple biological pathways and related genes. Finally, the expression levels of prognostic genes in STAD tissues and cell lines were verified using qRT-PCR, Western blot, and the Human Protein Atlas database. Taken together, the prognostic signature constructed in this study may become an indicator for clinical prognostic assessment of LNM-STAD and provide a new strategy for future targeted therapy.
Reporting perioperative complications of radical cystectomy: the influence of using standard methodology based on ICARUS and EAU quality criteria
Authors: Cinar Naci Burak , Yilmaz Hasan , Avci Ibrahim Erkut , Cakmak Kutlucan , Teke Kerem , Dillioglugil Ozdal
Published: February 2023

Purpose

We aimed to evaluate perioperative complications of radical cystectomy (RC) by using standardized methodology. Additionally, we identified independent risk factors associated with perioperative complications.

Materials and methods

We retrospectively analyzed 30-day and 90-day perioperative complications of 211 consecutive RC patients. The intraoperative and postoperative complications were defined according to Clavien-Dindo classification (CDC) and reported based on the ICARUS criteria, Martin, and EAU quality criteria. Age-adjusted Charlson comorbidity index (ACCI), systemic inflammatory response index (SIRI), body mass index (BMI) ≥ 25 kg/m2, and neoadjuvant chemotherapy (NAC) were also evaluated. Multivariable regression models according to severe (CDC ≥ IIIb grade) complications were tested.

Results

Overall, 88.6% (187/211) patients experienced at least one intraoperative complication. Bleeding during cystectomy was the most common complication observed (81.5% [172/211]). Severe intraoperative complications (EAUiaiC grade > 2) were recorded in 8 patients. Overall, 521 postoperative complications were recorded. Overall, 69.6% of the patients experienced complications. Thirty-nine patients suffered from most severe (CDC ≥ IIIb grade) complications. ACCI (OR: 1.492 [1.144–1.947], p = 0.003), SIRI (OR: 1.279 [1.029–1.575], p = 0.031), BMI (OR: 3.62 [1.58–8.29], p = 0.002), and NAC (OR: 0.342 [0.133–0.880], p = 0.025) were significant independent predictive factors for 90-day most severe complications (CDC ≥ IIIb grade).

Conclusions

RC complications were reported within a standardized manner, concordant with the ICARUS and Martin criteria and EAU guideline recommendations. Complication reporting seems to be improved with the use of standard methodology. Our results showed that ACCI, SIRI, and BMI ≥ 25 kg/m2 and the absence of NAC were significant predictive factors for most severe complications.
IL-6 as new prognostic factor in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab
Authors: Mallardo Domenico , Simeone Ester , Festino Lucia , Tuffanelli Marilena , Vanella Vito , Trojaniello Claudia , Vitale Maria Grazia , Ottaviano Margaret , Capone Mariaelena , Madonna Gabriele , Sparano Francesca , Cioli Eleonora , Scarpato Luigi , Palla Marco , Di Trolio Rossella , Meinardi Paolo , Caracò Corrado , Ferrara Gerardo , Muto Paolo , Cavalcanti Ernesta , Ascierto Paolo Antonio
Published: February 2023

Background

Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment.

Methods

Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study.

Results

Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy.

Conclusions

Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma.
Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry
Authors: Heming Michael , Müller-Miny Louisa , Rolfes Leoni , Schulte-Mecklenbeck Andreas , Brix Tobias J. , Varghese Julian , Pawlitzki Marc , Pavenstädt Hermann , Kriegel Martin A. , Gross Catharina C. , Wiendl Heinz , Meyer zu Hörste Gerd
Published: February 2023

Objective

Neurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without neurological manifestation.

Methods

Using flow cytometry, we retrospectively investigated paired cerebrospinal fluid (CSF) and blood samples of 28 CTD patients without neurological manifestation, 38 CTD patients with neurological manifestation (N-CTD), 38 non-inflammatory controls, and 38 multiple sclerosis (MS) patients, a paradigmatic primary neuroinflammatory disease.

Results

We detected an expansion of plasma cells in the blood of both N-CTD and CTD compared to non-inflammatory controls and MS. Blood plasma cells alone distinguished the clinically similar entities N-CTD and MS with high discriminatory performance (AUC: 0.81). Classical blood monocytes indicated higher disease activity in systemic lupus erythematosus (SLE) patients. Surprisingly, immune cells in the CSF did not differ significantly between N-CTD and CTD, while CD4+ T cells and the CD4+/CD8+ ratio were elevated in the blood of N-CTD compared to CTD. Several B cell-associated parameters partially overlapped in the CSF in MS and N-CTD. We built a machine learning model that distinguished N-CTD from MS with high discriminatory power using either blood or CSF.

Conclusion

We here find that blood flow cytometry alone surprisingly suffices to distinguish CTD with neurological manifestations from clinically similar entities, suggesting that a rapid blood test could support clinicians in the differential diagnosis of N-CTD.
Comparison of three techniques in the surgical management of metastatic vertebral fracture with posterior wall damage: a retrospective study
Authors: Wang Heng , Xie Jile , Liu Yijie , Chen Guangdong , Jiang Weimin
Published: February 2023

Background

To retrospectively compare the safety and efficacy of percutaneous kyphoplasty (PKP), internal fixation (IF), and kyphoplasty combined with internal fixation (KP + IF) in treating metastatic vertebral fracture (MVF) with posterior wall damage.

Methods

87 patients with MVF with posterior wall damage underwent surgery. In Group PKP, 36 patients underwent PKP; in Group IF, 20 patients underwent pedicle screw fixation; and in Group KP + IF, 31 patients underwent kyphoplasty combined with pedicle screw fixation. Operative time, intraoperative blood loss, clinical and radiological results, and complication rate in each group were evaluated and compared.

Results

Significant improvement on the VAS, ODI scores, vertebral height and local kyphotic angle (LKA) was noted in each group (P < 0.001). Group PKP and Group KP + IF achieved better pain relief than Group IF (P < 0.05). At postoperative 3 days, Group PKP had better pain relief than Group KP + IF (P < 0.05). At other follow-up time points, there were no differences between Group PKP and KP + IF (P > 0.05). Group KP + IF and Group IF were more efficacious than Group PKP in terms of height restoration and LKA correction (P < 0.05). Group KP + IF had a higher incidence of postoperative complications than Group PKP and Group IF(P < 0.05).

Conclusions

PKP was safe and effective in treating MVF with posterior wall damage. It can achieve similar clinical outcomes compared to KP + IF, but associated with less operative time, less blood loss and fewer complications. IF alone should not be the first treatment option for its poorer analgesic effect.
Finite element analysis of titanium anatomic plate and titanium reconstructive plate for treatment of extra-articular fractures of the scapula
Authors: Shang Yanliang , Bi Yunlong , Cao Yang , Wang Yansong
Published: February 2023

Background

Due to the lack of postoperative reporting outcomes and bio-mechanical studies, an optimal management of scapular fractures has not been well-established in clinical treatment, even though there are many options available. This study aimed to compare the stability of the new titanium anatomic and traditional titanium reconstructive plates for extra-articular scapular fractures through finite element analysis.

Methods

Two models of scapular assembly were constructed, including one anatomic plate (AP model) and one reconstructive plate (RP model). After meshing, material parameter, and boundary condition settings, we applied four loading conditions to simulate forces acting on the scapula and osteosynthesis material. To evaluate the bio-mechanical properties, the equivalent von Mises stress, equivalent elastic strain, and total deformation were investigated.

Result

The stress and strain distribution of model AP has better performance than model RP, with more uniform and lower values. The maximum stress value of the scapula in model AP is smaller than that of the scapula in model RP (102.83 MPa vs. 166.71 MPa). The maximum stress of the anatomic plate is half that of the reconstructive plate (218.34 MPa vs. 416.01 MPa). The maximum strain of the scapula in model AP is smaller than that of the scapula in model RP (0.0071 vs. 0.0106). The maximum strain of the anatomic plate is half that of the reconstructive plate (0.0019 vs. 0.0037). The maximum displacement of each model is all at the acromion, with a similar value (2.2947 mm vs. 1.8308 mm).

Conclusions

With sufficient bio-mechanical stability, the anatomic plate to support scapular fracture fragments was superior to that of the reconstructive plate.
Psychosocial implications of rare genetic skin diseases affecting appearance on daily life experiences, emotional state, self-perception and quality of life in adults: a systematic review
Authors: Fournier Hugo , Calcagni Nicolas , Morice-Picard Fanny , Quintard Bruno
Published: February 2023

Background

Since the beginning of human genetic research, there are very few publications sharing insights of the negative impact of rare genetic skin diseases (RGSD) on patients’ experiences. This systematic review assessed the psychosocial implications of these conditions in terms of daily life experiences, emotional state, self-perception, and Quality of Life (QoL).

Methodology

A systematic review was carried out on albinism, neurofibromatosis type 1 (NF1), birthmarks and inherited ichthyosis. The PubMed, Scopus, PsycArticle, PsychInfo, Psychology and Behavioral Sciences Collection, and SOCindex databases were queried. Inclusion criteria were adult patients with one of these RGSDs. Simple descriptive statistics and qualitative content analysis were conducted to summarize the main results reported by the authors.

Results

Of the 9987 articles retrieved, 48 articles were included: albinism (16), NF1 (16), inherited ichthyosis (10), birthmarks (6). The majority of the studies on albinism were conducted in Africa. Twenty-seven studies quantitatively assessed diverse psychological parameters: 13 showed a significant impact of the disease on QoL, five on emotional state, two on self-representation and two others on psychiatric comorbidities. Disease severity and visibility were good predictors of QoL (except for albinism). Body image and appearance concerns were also associated with QoL and emotional state. The 19 qualitative studies highlighted recurring themes across each of these diseases: discrimination and stigma during childhood and adolescence, discomfort in social interactions, guilt of transmission, the importance of social support from family and friends, altered daily life functioning, altered romantic and sex life, limited academic and professional aspirations, lack of interest and support from the medical field, and the unpredictability of the evolution of the disease. The only two mixed-method studies in this review were unable to contribute to any inferential analyses but could corroborate some of the qualitative findings.

Conclusion

These results showed that RGSDs have a significant impact on different aspects of patients’ lives. This review has demonstrated that there is a real need for support systems for patients with these diseases. Such systems should be developed to provide them with necessary information and to guide them through an appropriate care pathway.
Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study
Authors: Veldhoen Esther S. , Wijngaarde Camiel A. , van Eijk Ruben P. A. , Asselman Fay-Lynn , Seddiqi Negina , Otto Louise A. M. , Stam Marloes , Cuppen Inge , Wadman Renske I. , van Asperen Roelie M. Wösten , Hulzebos Erik H. J. , van den Oudenrijn Laura P. Verweij , Bartels Bart , Boezer Jasmijn , Gaytant M. , van der Ent Cornelis K. , van der Pol W. Ludo
Published: February 2023

Background

Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure.

Methods

We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PEmax). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure.

Results

We analyzed 385 lung function tests from 38 patients with SMA types 1c–3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2–30.1) and median standardized FVC, FEV1 and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PEmax was 35.3 cmH2O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV1, PEF and PEmax were lower in patients who electively started mechanical ventilation (p < 0.001).

Conclusions

Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function. We found no evidence for an accelerated deterioration. In addition, PEmax remains low and stable in the years preceding initiation of ventilation. Patients who electively started mechanical ventilation had more restrictive lung function at initiation of ventilation, compared to patients who could not be weaned after surgery or a respiratory tract infection.
Observation of the therapeutic effect of apatinib in advanced platinum-resistant recurrent epithelial ovarian cancer
Authors: Pan Zhongmian , Luo Zhongbin , He Hongying , Chen Yujie , Zhao Bingbing , Yang Zhijun , Li Li
Published: February 2023

Background

Apatinib is an oral anti-angiogenic drug that mainly targets vascular endothelial growth factor receptor 2 (VEGFR-2) and is widely used in a variety of solid tumours. The purpose of this study is to evaluate the clinical efficacy and safety of apatinib in patients with advanced platinum-resistant relapsed epithelial ovarian cancer (EOC).

Methods

A retrospective analysis was performed, the clinical data of patients with stage IIIC-IV platinum-resistant relapsed EOC between January 2014 and May 2018 were collected. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and evaluated. The propensity score matching (PSM) method was used to determine the final case data included in this study.

Results

According to 1:2 propensity matching, 108 patients were finally taken into account: 36 in the apatinib group and 72 in the control group. The follow-up ended in January 2019, and the median follow-up time was 28 months. In the apatinib group, ORR was 30.56% and DCR was 66.67%, whereas in the control group, ORR was 16.67% and DCR was 44.44%. In the apatinib group, median PFS was 6.0 months (95% CI 3.69–8.31) and median OS was 15.8 months (95% CI 6.99–24.6), while in the control group, median PFS was 3.3 months (95% CI 2.44–4.16) and median OS was 9.2 months (95% CI 6.3–12.06); the difference was statistically significant (P < 0.05). Apatinib was more effective than conventional chemotherapy in reducing the risk of PFS [HR 0.40 (95% CI 0.22–0.76), P = 0.0017] and OS [HR 0.40 (95% CI 0.21–0.73), P = 0.002]. Multivariate Cox analysis showed that the course of treatment and decrease in serum CA125 levels are independent risk factors for PFS in patients, while apatinib, the length of treatment course and the location of the lesion are independent risk factors for recurrence affecting the OS of patients. The main grade 3–4 adverse events in the apatinib group were hypertension, hand-foot syndrome, and oral mucosal ulcers, and all adverse events were controllable.

Conclusion

Apatinib was found to be both safe and effective in patients with advanced platinum-resistant relapsed EOC. More in-depth clinical research and applications should be carried out.
Pitfalls and opportunities for applying latent variables in single-cell eQTL analyses
Authors: Xue Angli , Yazar Seyhan , Neavin Drew , Powell Joseph E.
Published: February 2023

Using latent variables in gene expression data can help correct unobserved confounders and increase statistical power for expression quantitative trait Loci (eQTL) detection. The probabilistic estimation of expression residuals (PEER) and principal component analysis (PCA) are widely used methods that can remove unwanted variation and improve eQTL discovery power in bulk RNA-seq analysis. However, their performance has not been evaluated extensively in single-cell eQTL analysis, especially for different cell types. Potential challenges arise due to the structure of single-cell RNA-seq data, including sparsity, skewness, and mean-variance relationship. Here, we show by a series of analyses that PEER and PCA require additional quality control and data transformation steps on the pseudo-bulk matrix to obtain valid latent variables; otherwise, it can result in highly correlated factors (Pearson's correlation r = 0.63 ~ 0.99). Incorporating valid PFs/PCs in the eQTL association model would identify 1.7 ~ 13.3% more eGenes. Sensitivity analysis showed that the pattern of change between the number of eGenes detected and fitted PFs/PCs varied significantly in different cell types. In addition, using highly variable genes to generate latent variables could achieve similar eGenes discovery power as using all genes but save considerable computational resources (~ 6.2-fold faster).
Intraspecific variation of Quercus ilex L. seed morphophysiological traits in Tunisia reveals a trade-off between seed germination and shoot emergence rates along a thermal gradient
Authors: Amimi Nabil , Ghouil Hana , Zitouna-Chebbi Rim , Joët Thierry , Ammari Youssef
Published: February 2023

Key message

Quercus ilex populations from cold habitats display a large lag between seed germination and shoot emergence time, favouring avoidance of late frost events. Populations from mild habitats show the fastest seed germination and shoot emergence rates at moderate temperatures, enabling them to synchronize germination in the late winter-early spring period and a rapid seed-to-seedling transition, during the favourable rainy period.

Context

Quercus ilex is the most abundant and representative Mediterranean oak species. Identifying and describing intraspecific variation in seed traits is necessary to characterize the germination niche, and to elucidate drivers of species’ range.

Aims

In order to identify adaptations to local environments that may reflect ecological strategies for stress avoidance and seed survival, we tested under common and optimal conditions whether seed functional traits vary, in Quercus ilex subsp. rotundifolia Lam., along climatic gradients within its distribution range in Tunisia.

Methods

We have explored variations in seed morphological traits, desiccation sensitivity level, germination and shoot emergence rates under different controlled temperature conditions, among 15 populations of Q. ilex sampled throughout the Tunisian distribution of the species.

Results

Significant between-populations differences were observed for morphological seed traits but no relationships could be established with the climate of the sampling sites. In contrast, key physiological traits varied significantly with elevation and temperature. Specifically, mild temperatures in lowland regions were associated with higher seed moisture content, fast germination and shoot emergence rates at moderate temperatures (13 °C) for germination. Seeds of Q. ilex populations from cold sites displayed the fastest germination rates at low temperatures (5 °C) as well as the greatest lag between seed germination and shoot emergence time.

Conclusion

Intraspecific variation in seed physiological traits is significantly associated with local climate. This functional diversity should be considered when evaluating germplasm and predicting suitability for reforestation and assisted migration programs.
An inexact multiblock alternating direction method for grasping-force optimization of multifingered robotic hands
Authors: Zhang Yaling , Mu Xuewen
Published: February 2023

In this paper, we present an inexact multiblock alternating direction method for the point-contact friction model of the force-optimization problem (FOP). The friction-cone constraints of the FOP are reformulated as the Cartesian product of circular cones. We focus on the convex quadratic circular-cone programming model of the FOP, which is an exact cone-programming model. Coupled with the separable convex quadratic objective function, we recast the circular-cone-programming model as a multiblock separable cone model. A parallel inexact multiblock alternating direction method is used to solve the FOP. We prove the global convergence of the proposed method. Simulation results of the three-fingered FOP are reported, which verified the efficiency of the proposed method.
Development and Psychometric Validation of the Mental Health-Related Barriers and Benefits to EXercise (MEX) Scale in Healthy Adults
Authors: Connolly Madeleine L. , Bowden Stephen C. , Pascoe Michaela C. , Van Dam Nicholas T.
Published: February 2023

Background

Physical exercise has been shown to reduce anxiety and depression symptoms, the most common mental health disorders globally. Despite the benefits of exercise in anxiety and depression, the symptoms of these disorders may directly contribute to a lack of engagement with exercise. However, mental health-related barriers and benefits to exercise engagement have not been addressed in quantitative research. We introduce the development and psychometric validation of the Mental health-related barriers and benefits to EXercise (MEX) scale.

Methods

Three samples were collected online prospectively (sample 1 n = 492; sample 2 n = 302; sample 3 n = 303) for scale refinement and validation with exploratory and confirmatory factor analysis. All participants were generally healthy adults, aged 18–45, and had no history of severe mental illness requiring hospitalization and no physical disability impacting over 50% of daily function.

Results

We identified a 30-item, two-factor model comprising 15 barrier and 15 benefit items. Overall model fit was excellent for an item-level scale across the three samples (Comparative Fit Index = 0.935–0.951; Root-Mean-Square Error of Approximation = 0.037–0.039). Internal consistency was also excellent across the three samples (α = 0.900–0.951). The barriers subscale was positively correlated with symptoms of anxiety, depression and stress, and negatively correlated with measures of physical activity and exercise engagement. The benefits subscale was negatively correlated with symptoms of anxiety, depression and stress, and positively correlated with measures of physical activity and exercise engagement.

Conclusion

The MEX is a novel, psychometrically robust scale, which is appropriate for research and for clinical use to ascertain individual and/or group level mental health-related barriers and benefits to exercise.
The Relative Importance of Training and Social Support for Runners’ Performance: A Cross-Sectional Study
Authors: Thuany Mabliny , Vieira Douglas , de Paula Henrique , Nikolaidis Pantelis T. , Scheer Volker , Weiss Katja , Cuk Ivan , Knechtle Beat , Gomes Thayse Natacha
Published: February 2023

Background

Running participation/performance is a complex system. Understanding the variables associated with these behaviors may help to increase population physical activity and improve performance. This study aimed to investigate social and training variables important for running performance using a network approach.

Methods

This cross-sectional study sampled 1151 non-professional Brazilian runners of both sexes (women, 38.2%; men, 61.7%). A questionnaire was available for eligible participants using an online platform, and information regarding training (volume and running pace) and social variables (participation in a running event, participation in a running group, influence on running, runners in the family, and childhood sport) related to runners’ performance was obtained. The Chi-square test and network model were estimated by sex.

Results

Training characteristics tend to be clustered. For both sexes, the training volume node presented the highest expected influence in the network (1.69 for women and 2.16 for men). Centrality indicators of social variables show that sports childhood participation and the presence of runners in the family were the most important nodes of network connection for women and men, respectively.

Conclusion

Based on these findings, it was concluded that sports participation during childhood and the practice of running by other family members were important factors to connect variables in the network. These findings have practical applications for health policymakers, highlighting the need to develop educational programs to increase sports participation during childhood and within families.
Cancer Screening in the United States During the Second Year of the COVID-19 Pandemic
Authors: Star Jessica , Bandi Priti , Siegel Rebecca L. , Han Xuesong , Minihan Adair , Smith Robert A. , Jemal Ahmedin
Published: February 2023

PURPOSE

To examine whether cancer screening prevalence in the United States during 2021 has returned to prepandemic levels using nationally representative data.

METHODS

Information on receipt of age-eligible screening for breast (women age 50-74 years), cervical (women without a hysterectomy age 21-65 years), prostate (men age 55-69 years), and colorectal cancer (men and women age 50-75 years) according to the US Preventive Services Task Force recommendations was obtained from the 2019 and 2021 National Health Interview Survey. Past-year screening prevalence in 2019 and 2021 and adjusted prevalence ratios (aPRs), 2021 versus 2019, with their 95% CIs were calculated using complex survey logistic regression models.

RESULTS

Between 2019 and 2021, past-year screening in the United States decreased from 59.9% to 57.1% (aPR, 0.94; 95% CI, 0.91 to 0.97) for breast cancer, from 45.3% to 39.0% (aPR, 0.85; 95% CI, 0.82 to 0.89) for cervical cancer, and from 39.5% to 36.3% (aPR, 0.9; 95% CI, 0.84 to 0.97) for prostate cancer. Declines were most notable for non-Hispanic Asian persons. Colorectal cancer screening prevalence remained unchanged because an increase in past-year stool testing (from 7.0% to 10.3%; aPR, 1.44; 95% CI, 1.31 to 1.58) offset a decline in colonoscopy (from 15.5% to 13.8%; aPR, 0.88; 95% CI, 0.83 to 0.95). The increase in stool testing was most pronounced in non-Hispanic Black and Hispanic populations and in persons with low socioeconomic status.

CONCLUSION

Past-year screening prevalence for breast, cervical, and prostate cancer among age-eligible adults in the United States continued to be lower than prepandemic levels in the second year of the COVID-19 pandemic, reinforcing the importance of return to screening health system outreach and media campaigns. The large increase in stool testing emphasizes the role of home-based screening during health care system disruptions.

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Integration of Remote Symptom and Biometric Monitoring Into the Care of Adult Patients With Cancer Receiving Chemotherapy—A Decentralized Feasibility Pilot Study
Authors: Offodile Anaeze C. , Delgado Domenica , Lin Yu-Li , Geyen Danielle , Miller Christopher J. , Jain Sanchita , Finder Janice P. , Shete Sanjay , Fossella Frank V. , Overman Michael J. , Peterson Susan K.
Published: February 2023

PURPOSE:

Although electronic patient-reported outcomes (ePROs) are efficacious in symptom management, much is unknown about the utility of vital signs surveillance. We examined the feasibility of a remote patient monitoring platform that integrates ePROs and biometrics into the ambulatory management of symptom burden.

METHODS:

Using a decentralized workflow, patients with gastrointestinal or thoracic cancer were approached for a 1-month study. Patients reported symptom burden via ePROs and biometrics (blood pressure, oxygen saturation, pulse, weight, and temperature) using bluetooth-enabled devices daily. Alerts on the basis of prespecified thresholds were managed via nurse-led triage. Adherence was defined as the completion of > 70% of daily symptom and biometric reporting requirements. Pilot acceptability, appropriateness, and feasibility were measured using validated instruments. Net promoter score, system usability scale, and emergency department (ED) admission rates were collected.

RESULTS:

Over 8 months, 36 patients were enrolled and 25 (60% gastrointestinal) completed the study. Participants had a mean age of 58.0 years, mean Eastern Cooperative Oncology Group score of 0.88, were 52% female, and predominantly had stage IV or recurrent disease (72%). Program adherence was 73% and associated with high acceptability (4.63), feasibility (4.56), and appropriateness (4.46). System usability scale and net promoter score scores were 88 and 55, respectively. Seventy percent of alerts were generated by biometrics, 28% for symptoms, and 2% were patient-initiated communication. Finally, the ED visitation rate over the pilot period was 8%.

CONCLUSION:

Our remote patient monitoring pilot program was highly acceptable, feasible, and appropriate. It had high rates of patient adherence and satisfaction and was associated with low ED visitation rates.
Impact Of Physical Activity And Health Education On The Development Of Depression
Authors: Kulbat Aleksandra , Karwańska Aleksandra , Kulbat Mateusz , Brzychczy Piotr , Majcher Magdalena , Górska Dominika , Sierpień Małgorzata , Majcher Monika , Świercz Kamila , Pikulicka Agata
Published: February 2023

Depression is a common mental health disorder that affects the majority of the population. The exact cause of depression is not fully understood, but various factors such as genetics, environmental stressors, and psychological factors are believed to play a role. Due to the complexity of the etiopathogenesis of depression, the selection of appropriate therapeutic management is sometimes complicated. Treatment for depression typically involves a combination of medication and psychotherapy. Antidepressant medication can help alleviate symptoms by regulating neurotransmitters in the brain, while psychotherapy can help individuals understand and change negative thoughts and behaviors.

Physical activity, such as sport, has been shown to have a positive impact on mental health and can help alleviate symptoms of depression. Exercise releases endorphins, reducing stress and improving mood. Health education can also play a role in preventing and managing depression by raising awareness, reducing stigma, and teaching individuals coping skills to maintain good mental health.