bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study
Authors: Drysdale Myriam , Tibble Holly , Patel Vishal , Gibbons Daniel C. , Lloyd Emily J. , Kerr William , Macdonald Calum , Birch Helen J. , Sheikh Aziz
Published: July 2024

Background

The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland.

Methods

Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021–October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed.

Results

In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients.

Conclusions

Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.
Spanish experts consensus on emergency psychiatric care in hospital emergency departments
Authors: Gordillo-Urbano Rafael Manuel , Crespo-Facorro Benedicto , Pérez-Solá Víctor , Cardoner Narcís , García-Ligero Elena , Moreno Carmen , Ramos-Quiroga Josep Antoni , Ruiz-Veguilla Miguel , Vázquez-Vallejo Mireia , Prados-Ojeda Juan Luis ,   the Spanish Expert Group in Emergency Psychiatric Care
Published: July 2024

Background

The demand for urgent psychiatric care is increasing, but in Spain there are no clear recommendations for emergency departments (ED) on how to optimize care for patients with psychiatric emergencies. We aimed to provide expert consensus recommendations on the requirements for general hospitals´ emergency departments to treat patients with urgent psychiatric symptoms.

Methods

We used a modified Delphi technique. A scientific committee compiled 36 statements based on literature search and clinical experience. The statements covered the organizational model, facilities, staffing, safety, patient interventions, and staff training. A panel of 38 psychiatry specialists with expertise in psychiatric emergencies evaluated the questionnaire in two rounds.

Results

After two rounds of voting, 30 out of 36 proposed items (83%) were agreed upon. The panel agreed that psychiatric emergencies should be managed in a general hospital, with dedicated facilities for patient assessment, direct supervision of patients at risk, and an observation unit run by the psychiatric service. In addition to the psychiatrist, the ED should have specialist nurses and security staff available 24/7. Social workers should also be readily available. ED and consulting rooms should be designed to ensure patient and staff safety. A triage system should be established for patients with psychiatric symptoms, with medical evaluation preceding psychiatric evaluation. Guidance on supplies, equipment, and staff training is also provided.

Conclusion

All ED in general hospitals should have adequate resources to handle any psychiatric emergency. This paper provides recommendations on the minimum requirements to achieve this goal.
Types of leisure-time physical activity participation in childhood and adolescence, and physical activity behaviours and health outcomes in adulthood: a systematic review
Authors: Miller Kelcie , Morley Claire , Fraser Brooklyn J. , Gall Seana L. , Cleland Verity
Published: July 2024

Background

Youth leisure-time physical activity participation benefits physical activity habits and health outcomes later in life. However, it is unknown if certain types of leisure-time physical activity contribute to these benefits in different ways; this knowledge could enhance public health efforts. This systematic review aimed to synthesise evidence of the longitudinal associations between childhood and adolescent leisure-time physical activity on adulthood physical activity behaviours and health outcomes.

Methods

A systematic search of the literature was conducted across five databases from inception to July 2022. English, peer-reviewed observational studies with a minimum of two timepoints of data collection were eligible for inclusion. We included studies that investigated the association between participation in leisure-time physical activity types in children and adolescents (i.e., 5–18 years), and physical activity, mental health, or cardiovascular outcomes in adulthood (i.e., ≥ 18 years).

Results

Fourteen studies were included in the review, totalling 34,388 observations across five countries. Running in adolescence was associated with increased adulthood physical activity in both sexes, while sports involvement was associated with an increase in physical activity in males only. Adolescent team sports participation was associated with reduced odds of early adulthood depression, with varying findings for anxiety disorders. There was preliminary evidence of minimum threshold requirements for participation in certain activities before associations with future physical activity or health outcome benefits were observed.

Conclusions

Preliminary findings suggest that the lifelong behavioural and health benefits of adolescent participation in leisure-time physical activity appear to be related to the type of activity undertaken, with potential differences between sexes. With the rarity of longitudinal studies spanning from childhood into adulthood, these findings provide important insights for public health strategies to optimise lifelong health and physical activity participation.

Prospero registration

CRD42022347792.
WeChat usage and preservation of cognitive functions in middle-aged and older Chinese adults: indications from a nationally representative survey, 2018–2020
Authors: Zhou Yan , Abuduxukuer KaiweiSa , Wang Chuchu , Wei Jin , Shi Wenming , Li Yongzhen , Huang Guang , Zhou Yifan , Zhang Yunfeng , Luo Jianfeng
Published: July 2024

Purpose

To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey.

Methods

In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings.

Results

After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values<0.05). Such results remained robust in subgroup analyses, stratified by age and gender, and also verified according to longitudinal analyses. Compared to ‘Chat-only’ users who only used WeChat for online interpersonal communication, further usage of WeChat functions such as using ‘Moments’ appeared to be significantly associated with better cognitive performance, especially for episodic memory.

Conclusion

Social media usage is significantly and positively associated with better cognitive performance among the middle-aged and older Chinese population. Along with point-to-point messaging, using ‘Moments’ and extended social media platform functions may correlate to better cognitive performance.
Determinants of intended prevention behaviour against mosquitoes and mosquito-borne viruses in the Netherlands and Spain using the MosquitoWise survey: cross-sectional study
Authors: de Best Pauline A. , Abourashed Ayat , Doornekamp Laura , van Gorp Eric C. M. , Timen Aura , Sikkema Reina S. , Bartumeus Frederic , Palmer John R. B. , Koopmans Marion P. G.
Published: July 2024

Background

Recently, Europe has seen an emergence of mosquito-borne viruses (MBVs). Understanding citizens’ perceptions of and behaviours towards mosquitoes and MBVs is crucial to reduce disease risk. We investigated and compared perceptions, knowledge, and determinants of citizens’ behavioural intentions related to mosquitoes and MBVs in the Netherlands and Spain, to help improve public health interventions.

Methods

Using the validated MosquitoWise survey, data was collected through participant panels in Spain (N = 475) and the Netherlands (N = 438). Health Belief Model scores measuring behavioural intent, knowledge, and information scores were calculated. Confidence Interval-Based Estimation of Relevance was used, together with potential for change indexes, to identify promising determinants for improving prevention measure use.

Results

Spanish participants’ responses showed slightly higher intent to use prevention measures compared to those of Dutch participants (29.1 and 28.2, respectively, p 0.03). Most participants in Spain (92.2%) and the Netherlands (91.8%) indicated they used at least one prevention measure, but differences were observed in which types they used. More Spanish participants indicated to have received information on mosquitoes and MBVs compared to Dutch participants. Spanish participants preferred health professional information sources, while Dutch participants favoured government websites. Determinants for intent to use prevention measures included “Knowledge”, “Reminders to Use Prevention Measures”, and “Information” in the Netherlands and Spain. Determinants for repellent use included “Perceived Benefits” and “Cues to Action”, with “Perceived Benefits” having a high potential for behavioural change in both countries. “Self-Efficacy” and “Knowledge” were determinants in both countries for breeding site removal.

Conclusion

This study found differences in knowledge between the Netherlands and Spain but similarities in determinants for intent to use prevention measures, intent to use repellents and intent to remove mosquito breeding sites. Identified determinants can be the focus for future public health interventions to reduce MBV risks.
Gender-based violence and harassment at work and health and occupational outcomes. A systematic review of prospective studies
Authors: Blindow Katrina J. , Cedstrand Emma , Elling Devy L. , Hagland Malin , Bodin Theo
Published: July 2024

Background

Many people experience forms of gender-based violence and harassment (GBVH) in the context of their work. This includes a wide range of experiences, from subtle expressions of hostility to physical assault, that can also be of a sexual nature (e.g., sexual harassment or assault). This systematic review aimed to summarize findings about the prospective associations of work-related GBVH with people’s health and occupational situation.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Scopus, Web of Science, MEDLINE and PsycINFO were searched for prospective studies in English from 1990 to May 24, 2023. Studies were included if they concerned a working population, exposure to any form of GBVH in the work context, and a health outcome or manifest occupational outcome. Quality was assessed with a modified version of the Cochrane ‘Tool to Assess Risk of Bias in Cohort Studies’, and studies assessed as low quality were excluded from the narrative synthesis. For the narrative synthesis, we grouped the results by similar exposures and outcomes and reported the strength and statistical significance of the associations.

Results

Of the 1 937 screened records, 29 studies were included in the narrative synthesis. Studies were mainly conducted in the USA and northern Europe and investigated exposure to sexual violence or harassment (SVH). Only two included studies investigated non-sexual kinds of GBVH. Consistently, studies showed associations of work-related SVH with poor mental health and there were indications of an association with hazardous substance use. There was no consistent evidence for an association of SVH with subsequent sickness absence, and there were too few studies concerning physical health and occupational outcomes to synthesize the results.

Conclusions

There is consistent evidence of work-related SVH as a risk factor for subsequent poor mental health. There is no indication that the health consequences of SVH differ between women and men, although women are more often affected. There is a need for conceptual consistency, the consideration of non-sexual behaviors and prospective studies that test clear hypotheses about the temporal sequence of events.
Prevalence and disease burden of chronic cough in nine cities of China: an observational study
Authors: Chen Lin , Lao Kim S.J. , Yi Fang , Xia Kai , Lai Kefang
Published: July 2024

Background

Chronic cough (CC) is common in the general population of China, creating a difficult-to-ignore public health burden. However, there is a lack of research on the nationwide prevalence and disease burden of CC in the Chinese population. We aim to use an insurance claims database to assess the prevalence and the corresponding economic burden owing to CC in China.

Methods

This was a retrospective observational study based on an administrative medical insurance database in 2015, 2016 and 2017, from nine cities in North, South, East, South-West, and North-West regions of China. The study population was Chinese adults (≥ 18 years old) who had been identified as CC patients. Descriptive data analyses were used in statistical analysis.

Results

A total of 44,472, 55,565, and 56,439 patients with mean ages of 53.2 (16.3) years were identified as patients with CC in 2015, 2016, and 2017, respectively. Of these, 55.24% were women. In addition, 8.90%, 9.46%, and 8.37% of all patients in 2015, 2016, and 2017, who had applied for medical insurance, had CC, respectively, with a three-year average probability of 8.88%. The median number of outpatient visits within a calendar year was 27 per year due to any reason during the period of 2015–2017. The median medical cost of each patient per year increased from 935.30 USD to 1191.47 USD from 2015 to 2017.

Conclusion

CC is common among medical insurance users, with a substantial utilization of medical resources, highlighting the huge burden of CC in China.
Bioelectrical impedance and lung function—associations with gender and central obesity: results of the EpiHealth study
Authors: Qvarfordt Mikaela , Lampa Erik , Cai Gui-Hong , Lind Lars , Elmståhl Sölve , Svartengren Magnus
Published: July 2024

Background

Obesity is a major public health concern associated with various health problems, including respiratory impairment. Bioelectrical impedance (BIA) is used in health screening to assess body fat. However, there is no consensus in healthcare on how body fat should be assessed in relation to lung function. In this study, we aimed to investigate how BIA in relation to waist circumference contribute, using data from a large Swedish population study.

Methods

A total of 17,097 participants (aged 45–75 years) were included in the study. The relationships between fat mass, waist circumference, and lung function were analysed using weighted quantile sum regression.

Results

Increased fat mass was significantly associated with decreased lung function (FEV1, FVC) in both sexes. Also, the influence of trunk fat and waist circumference on FVC and FEV1 differed by sex: in males, waist circumference and trunk fat had nearly equal importance for FVC (variable weights of 0.42 and 0.41), whereas in females, trunk fat was significantly more important (variable weights 0.84 and 0.14). For FEV1, waist circumference was more important in males, while trunk fat was more significant in females (variable weights male 0.68 and 0.28 and 0.23 and 0.77 in female).

Conclusions

Our results suggest that trunk fat should be considered when assessing the impact of adipose tissue on lung function and should potentially be included in the health controls.
Application of root cause analysis and TEAMSTEPPS post intravesical gas explosion during transurethral resection of the prostate: a rare case report
Authors: Chen I-Hung , Fong Cher-Min , Chang Hsing-Hua Stella , Ni Ying-Jui , Chiu Kon-Ning , Lee Kai-Wen
Published: July 2024

Background

An intravesical gas explosion is a rare complication of transurethral resection of the prostate (TURP). It was first reported in English literature in 1926, and up to 2022 were only forty-one cases. Injury from an intravesical gas explosion, in the most severe cases appearing as extraperitoneal or intraperitoneal bladder rupture needed emergent repair surgery.

Case presentation

We present a case of a 75-year-old man who suffered an intravesical gas explosion during TURP. The patient underwent an emergent exploratory laparotomy for bladder repair and was transferred to the intensive care unit for further observation and treatment. Under the medical team’s care for up to sixty days, the patient recovered smoothly without clinical sequelae.

Conclusions

This case report presents an example of a rare complication of intravesical gas explosion during TURP, utilizing root cause analysis (RCA) to comprehend causal relationships and team strategies and tools to improve performance and patient safety (TeamSTEPPS) method delivers four teamwork skills that can be utilized during surgery and five recommendations to avoid gas explosions during TURP to prevent the recurrence of medical errors. In modern healthcare systems, promoting patient safety is crucial. Once complications appear, RCA and TeamSTEPPS are helpful means to support the healthcare team reflect and improve as a team.
Shaping tomorrow’s dentists: a multi-institutional survey of undergraduate dental students’ perceptions towards interprofessional education
Authors: Lin Galvin Sim Siang , Ng Yook Shiang , Hashim Hasnah , Foong Chan Choong , Yahya Noor Azlin , Halil Mohd Haikal Muhamad , Ahmad Mas Suryalis
Published: July 2024

Background

Interprofessional education (IPE) is essential to foster collaboration among healthcare professionals for holistic patient care. However, Malaysian dental education remains discipline-centric, hindering multidisciplinary learning approaches. Hence, this study aimed to explore Malaysian undergraduate dental students’ perceptions of IPE.

Methods

The present cross-sectional study employed convenience sampling to survey undergraduate dental students from four Malaysian institutions using a modified questionnaire with 20 close-ended and 2 open-ended questions. The questionnaire covered three domains (effectiveness, preference, importance) to assess students’ perceptions using a five-point Likert scale. Psychometric validation was performed to assure validity and reliability of the modified questionnaire. Quantitative analysis (descriptive and inferential statistics), and qualitative analysis (content analysis) were subsequently performed.

Results

397 students responded, and positive perceptions were generally noted with mean scores ranging from 4.13 to 4.35 across all domains. Questions 2 and 3, assessing the improvement in understanding the roles and responsibilities, and communication among healthcare professionals, received the highest mean scores. Meanwhile, Question 15 concerning the incorporation of IPE into educational goals received the lowest mean score. Regression analysis identified gender and clinical phase as significant factors, with females and preclinical students exhibiting more favourable perceptions. Motivators for IPE included a keen interest in diverse perspectives and recognising the importance of teamwork, while barriers encompassed tightly packed schedules, lack of understanding about IPE, misconceptions regarding dental education, and students’ nervousness and fear of participation.

Conclusion

This study produced a valid and reliable instrument to measure undergraduate dental students’ perceptions towards IPE. Strategic planning, such as overcoming logistical challenges, improving awareness, and creating a supportive learning environment are crucial for successful IPE integration into existing curricula, especially in resource-constrained developing countries like Malaysia.
Prevalence of traditional eye medicine and self-treatment in Gurage Zone, Rural Ethiopia
Authors: Sherief Sadik Taju , Sitotaw Munira Sherefedin , Girma Abonesh
Published: July 2024

Introduction

Traditional medicines are commonly used worldwide, especially in Africa—however, there is limited information on the prevalence and types of traditional eye medicine utilization in Ethiopia. The goal of this study was to determine the prevalence, the type and nature of traditional eye medicine use and practices related to self-medication for ophthalmic diseases in a rural Ethiopian population.

Methods

A cross-sectional study was conducted in six randomly selected primary health centers in rural Gurage Zone, Southern Ethiopia. Health-seeking behavior, use of self-medication, and traditional eye medicine were assessed in the population using a semi-structured questionnaire.

Descriptive statistics and multivariable logistic regression analysis were computed to determine associated factors for using self-medication and traditional eye medicine.

Result

Of the 814 participants interviewed, 487 (59.8%) reported using traditional eye medicine, mainly for combinations of symptoms of ocular redness, irritation, and eye discharge (95.5%). Besides, 604 (74.2%) participants reported self-treatment with tetracycline 1% eye ointment. Older age, females, low income, no formal education, and lack of access to media were risks for utilizing traditional eye medicine.

Conclusion

The use of traditional eye medicine and self-treatment are common in this population. Regulatory legislation, public awareness, and making eye care are vital activities required to monitor such practices.
Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank
Authors: Sun Tao , Yang Juan , Lei Fang , Huang Xuewei , Liu Weifang , Zhang Xingyuan , Lin Lijin , Sun Linsu , Xie Xinlan , Zhang Xiao-Jing , Cai Jingjing , She Zhi-Gang , Xu Chengsheng , Li Hongliang
Published: July 2024

Background

Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM).

Methods

This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed.

Results

In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%.

Conclusions

Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers’ artificial sweeteners consumption behavior.
The characteristics of eating, drinking and oro-pharyngeal swallowing difficulties associated with repaired oesophageal atresia/tracheo-oesophageal fistula: a systematic review and meta-proportional analysis
Authors: Stewart Alexandra , Govender Roganie , Eaton Simon , Smith Christina H. , De Coppi Paolo , Wray Jo
Published: July 2024

Introduction

Eating, drinking and swallowing difficulties are commonly reported morbidities for individuals born with OA/TOF. This study aimed to determine the nature and prevalence of eating, drinking and oro-pharyngeal swallowing difficulties reported in this population.

Method

A systematic review and meta-proportional analysis were conducted (PROSPERO: CRD42020207263). MEDLINE, EMBASE, CINAHL, Pubmed, Scopus, Web of Science databases and grey literature were searched. Quantitative and qualitative data were extracted relating to swallow impairment, use of mealtime adaptations and eating and drinking-related quality of life. Quantitative data were summarised using narrative and meta-proportional analysis methods. Qualitative data were synthesised using a meta-aggregation approach. Where quantitative and qualitative data described the same phenomenon, a convergent segregated approach was used to synthesise data.

Results

Sixty-five studies were included. Six oro-pharyngeal swallow characteristics were identified, and pooled prevalence calculated: aspiration (24%), laryngeal penetration (6%), oral stage dysfunction (11%), pharyngeal residue (13%), nasal regurgitation (7%), delayed swallow initiation (31%). Four patient-reported eating/drinking difficulties were identified, and pooled prevalence calculated: difficulty swallowing solids (45%), difficulty swallowing liquids (6%), odynophagia (30%), coughing when eating (38%). Three patient-reported mealtime adaptations were identified, and pooled prevalence calculated: need for water when eating (49%), eating slowly (37%), modifying textures (28%). Mixed methods synthesis of psychosocial impacts identified 34% of parents experienced mealtime anxiety and 25% report challenging mealtime behaviours reflected in five qualitative themes: fear and trauma associated with eating and drinking, isolation and a lack of support, being aware and grateful, support to cope and loss.

Conclusions

Eating and drinking difficulties are common in adults and children with repaired OA/TOF. Oro-pharyngeal swallowing difficulties may be more prevalent than previously reported. Eating, drinking and swallowing difficulties can impact on psychological well-being and quality of life, for the individual and parents/family members. Long-term, multi-disciplinary follow-up is warranted.
Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy
Authors: Gao Huanyao , Wei Lixuan , Indulkar Shreya , Nguyen Thanh Thanh. L. , Liu Duan , Ho Ming-Fen , Zhang Cheng , Li Hu , Weinshilboum Richard M. , Ingle James N. , Wang Liewei
Published: July 2024

Background

Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80–90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies.

Methods

We performed a genome-wide study to identify hormone/drug-induced single nucleotide polymorphism (SNP) genotype - dependent gene-expression, known as PGx-eQTL, mediated by either an AR agonist (dihydrotestosterone) or a partial antagonist (enzalutamide), utilizing a previously well characterized lymphoblastic cell line panel. The association of the identified SNPs-gene pairs with breast cancer phenotypes were then examined using three genome-wide association (GWAS) studies that we have published and other studies from the GWAS catalog.

Results

We identified 13 DHT-mediated PGx-eQTL loci and 23 Enz-mediated PGx-eQTL loci that were associated with breast cancer outcomes post ER antagonist or aromatase inhibitors (AI) treatment, or with pharmacodynamic (PD) effects of AIs. An additional 30 loci were found to be associated with cancer risk and sex-hormone binding globulin levels. The top loci involved the genes IDH2 and TMEM9, the expression of which were suppressed by DHT in a PGx-eQTL SNP genotype-dependent manner. Both of these genes were overexpressed in breast cancer and were associated with a poorer prognosis. Therefore, suppression of these genes by AR agonists may benefit patients with minor allele genotypes for these SNPs.

Conclusions

We identified AR-related PGx-eQTL SNP-gene pairs that were associated with risks, outcomes and PD effects of endocrine therapy that may provide potential biomarkers for individualized treatment of breast cancer.
PromptSMILES: prompting for scaffold decoration and fragment linking in chemical language models
Authors: Thomas Morgan , Ahmad Mazen , Tresadern Gary , de Fabritiis Gianni
Published: July 2024

SMILES-based generative models are amongst the most robust and successful recent methods used to augment drug design. They are typically used for complete de novo generation, however, scaffold decoration and fragment linking applications are sometimes desirable which requires a different grammar, architecture, training dataset and therefore, re-training of a new model. In this work, we describe a simple procedure to conduct constrained molecule generation with a SMILES-based generative model to extend applicability to scaffold decoration and fragment linking by providing SMILES prompts, without the need for re-training. In combination with reinforcement learning, we show that pre-trained, decoder-only models adapt to these applications quickly and can further optimize molecule generation towards a specified objective. We compare the performance of this approach to a variety of orthogonal approaches and show that performance is comparable or better. For convenience, we provide an easy-to-use python package to facilitate model sampling which can be found on GitHub and the Python Package Index.

Scientific contribution

This novel method extends an autoregressive chemical language model to scaffold decoration and fragment linking scenarios. This doesn’t require re-training, the use of a bespoke grammar, or curation of a custom dataset, as commonly required by other approaches.
The use of Guyton’s approach to the control of cardiac output for clinical fluid management
Authors: Magder Sheldon
Published: July 2024

Infusion of fluids is one of the most common medical acts when resuscitating critically ill patients. However, fluids most often are given without consideration of how fluid infusion can actually improve tissue perfusion. Arthur Guyton’s analysis of the circulation was based on how cardiac output is determined by the interaction of the factors determining the return of blood to the heart, i.e. venous return, and the factors that determine the output from the heart, i.e. pump function. His theoretical approach can be used to understand what fluids can and cannot do. In his graphical analysis, right atrial pressure (RAP) is at the center of this interaction and thus indicates the status of these two functions. Accordingly, trends in RAP and cardiac output (or a surrogate of cardiac output) can provide important guides for the cause of a hemodynamic deterioration, the potential role of fluids, the limits of their use, and when the fluid is given, the response to therapeutic interventions. Use of the trends in these values provide a physiologically grounded approach to clinical fluid management.
Correction of nonmonotone trust region algorithm based on a modified diagonal regularized quasi-Newton method
Authors: Mirzaei Seyed Hamzeh , Ashrafi Ali
Published: July 2024

In this paper, a new appropriate diagonal matrix estimation of the Hessian is introduced by minimizing the Byrd and Nocedal function subject to the weak secant equation. The Hessian estimate is used to correct the framework of a nonmonotone trust region algorithm with the regularized quasi-Newton method. Moreover, to counteract the adverse effect of monotonicity, we introduce a new nonmonotone strategy. The global and superlinear convergence of the suggested algorithm is established under some standard conditions. The numerical experiments on unconstrained optimization test functions show that the new algorithm is efficient and robust.
Influence of rainfall changes from 4.6 to 3.0 ka BP on ceramic pipes
Authors: Wang Shuaiqi , Zhu Xiangyu , Tian Ye
Published: July 2024

The impact of climate change on human social development has been a topic of research for a long time. Ceramic pipes, which are vital components of urban drainage engineering, are crucial means of managing rain hazards and floods. Exploring the historical evolution of ceramic pipes can help in better understanding the interplay between climate change and human behavior. This study examined the diameters of 86 ceramic pipes unearthed from six cultural sites in central China, including Pingliangtai, Taosi, and Erlitou, dated to 4600–3040 a BP. By combining speleothem records from the excavation sites with precipitation and temperature composite curves for China using Pearson correlation analysis, and verifying with pollen records. The results show that changes in rainfall were the main factor influencing the diameters of the ceramic pipes. This indicates that during this period, ancient people in the Central Plains of China were able to adjust the size of the ceramic pipes to regulate the water management capacity of urban water systems, thereby adapting urban development to climate change.
Digital restoration and reconstruction of heritage clothing: a review
Authors: Ding Qian-Kun , Liang Hui-E
Published: July 2024

Historical, folk, and opera costumes are part of cultural heritage, embodying the history, culture, art, and spirit of given nations. Due to aging and various damages, handed-down and unearthed historical clothing is often fragile and complex to preserve. Recently, digital methods have emerged as a meaningful way to restore and reconstruct all kinds of heritage clothing. The appearance of heritage costumes can be preserved permanently and presented to the public in a more accessible and interesting way via digitization. However, there is a lack of systematic review on this topic. To fill this gap, recent progress in digital restoration and 3D virtual reconstruction of heritage clothing is reviewed in this article. On the one hand, the methods and advantages of digitally restoring damaged archaeological costumes and fabrics, as well as damaged clothing images in archaeological murals, are summarized and emphasized. On the other hand, the digital reconstruction and virtual simulation of heritage costumes from different prototypes with known or unknown original appearances using different digital frameworks are presented and discussed. Furthermore, general steps and challenges in the digital reconstruction process, as well as future directions for digitalizing heritage clothing, are also discussed.
Stable estimation of the Gutenberg–Richter b-values by the b-positive method: a case study of aftershock zones for magnitude-7 class earthquakes
Authors: Mitsui Yuta
Published: July 2024

The traditional approach for estimating the b-value of the Gutenberg–Richter law, which is posited to inversely correlate with differential stress, has historically relied on the maximum likelihood technique, utilizing data from earthquakes exceeding a magnitude cutoff, Mc. This traditional approach is significantly influenced by the value of Mc, leading to extensive research focused on methods for determining Mc with greater accuracy. However, a recent study introduced a novel method based on the frequency distribution of magnitude difference, termed the b-positive method. This innovative method could enable more robust b-value estimations, even in scenarios where Mc may vary spatially and temporally. Our study concentrated on analyzing aftershocks, related to 25 magnitude-7 class earthquakes surrounding the Japanese archipelago. We estimated the b-values using both the goodness-of-fit test for Mc, a traditional approach, and the b-positive method. The aftershock data were examined over two distinct time frames: the initial 10 days following each mainshock and an extended period of 1000 days. Our findings indicated that the estimates produced by the b-positive method showed negligible variation between the 10-day and 1000-day aftershock periods (correlation coefficient of 0.95), whereas the traditional approach tended to yield lower b-values for the 10-day aftershocks compared to those from the 1000-day period. Variations in b-values, when analyzed using the traditional approach, could be inaccurately ascribed to temporal fluctuations in differential stress that may not actually be present. The b-positive method offers a vital solution to prevent these erroneous interpretations, serving as an essential alternative.

Graphical abstract
Prevalence of osteoporosis and associated factors among people aged 50 years and older in the Madhesh province of Nepal: a community-based cross-sectional study
Authors: Chaudhary Narendra Kumar , Sunuwar Dev Ram , Sapkota Manish Raj , Pant Suman , Pradhan Mary , Bhandari Kailash Kumar
Published: July 2024

Background

The high prevalence of osteoporosis has increased the economic burden on the health system globally. The burden of osteoporosis and its associated factors have not been adequately assessed in community settings in the Nepalese context thus far. Therefore, this study aimed to assess the prevalence of osteoporosis and its associated factors, lifestyle behaviors, and dietary calcium intake.

Methods

A community-based cross-sectional study was conducted among 395 people aged 50 years and older in the Madhesh Province of Nepal between July 2022 and August 2023. The Osteoporosis Self-assessment Tools for Asians (OSTA) index was used to measure osteoporosis. A structured questionnaire was used to collect sociodemographic information, anthropometric data, lifestyle behavior, daily dietary calcium intake, and frequency of calcium-rich food consumption. A food frequency questionnaire and 24-hour recall methods were used to assess dietary intake. The chi-square test, binary logistic regression and Mann‒Whitney U test were applied to measure the association between predictors and the outcome of interest.

Results

The prevalence of no risk, moderate risk and high risk of osteoporosis were 38.7%, 39%, and 22.3% respectively. The risk of osteoporosis was higher in females (aOR = 5.18, CI: 2.10-12.75, p < 0.001) and increased risk with advancing age (aOR = 32.49, CI: 14.02–75.28, p < 0.001). Similarly, underweight was associated with increased odds of having osteoporosis (aOR = 13.42, CI = 4.58–39.30, p < 0.001). The incidence of osteoporosis was strongly associated with daily calcium intake of 225 mg (100, 386).

Conclusion

This study revealed a high prevalence of osteoporosis among people aged 50 years and older due to the combined effect of being underweight and having inadequate calcium intake. Nutritional counselling services encourage people to consume sufficient calcium-rich food and adopt an appropriate lifestyle behaviours to maintain healthy body weight so that osteoporosis and osteoporotic fractures could be prevented. Further research can explore the impact of socioeconomic status and medical comorbidities on a large scale.
Use of airborne LiDAR to predict fine dead fuel load in Mediterranean forest stands of Southern Europe
Authors: Lin Di , Giannico Vincenzo , Lafortezza Raffaele , Sanesi Giovanni , Elia Mario
Published: July 2024

Background

Mediterranean forests are increasingly threatened by wildfires, with fuel load playing a crucial role in fire dynamics and behaviors. Accurate fuel load determination contributes substantially to the wildfire monitoring, management, and prevention. This study aimed to evaluate the effectiveness of airborne Light Detection and Ranging (LiDAR) data in estimating fine dead fuel load, focusing on the development of models using LiDAR-derived metrics to predict various categories of fine dead fuel load. The estimation of fine dead fuel load was performed by the integration of field data and airborne LiDAR data by applying multiple linear regression analysis. Model performance was evaluated by the coefficient of determination (R2), root mean squared error (RMSE), and mean absolute error (MAE).

Results

Through multiple linear regression models, the study explored the relationship between LiDAR-derived height and canopy cover metrics and different types of fine dead fuel load (1-h, 10-h, 100-h fuel loads, and litter). The accuracy of these models varied, with litter prediction showing the highest accuracy (R2 = 0.569, nRMSE = 0.158). In contrast, the 1-h fuel load prediction was the least accurate (R2 = 0.521, nRMSE = 0.168). The analysis highlighted the significance of specific LiDAR metrics in predicting different fuel loads, revealing a strong correlation between the vertical structure of vegetation and the accumulation of fine dead fuels.

Conclusions

The findings demonstrate the potential of airborne LiDAR data in accurately estimating fine dead fuel loads in Mediterranean forests. This capability is significant for enhancing wildfire management, including risk assessment and mitigation. The study underscores the relevance of LiDAR in environmental monitoring and forest management, particularly in regions prone to wildfires.
Biventricular repair in low-weight patient with interrupted aortic arch and aortic atresia
Authors: Soynov Ilya A. , Arkhipov Alexey N. , Manukian Serezha N. , Kulyabin Yuriy Y. , Kobelev Evgeniy , Malakhova Oksana Y. , Voitov Alexey V. , Suzdalova Olga A.
Published: July 2024

Background

Aortic atresia with ventricular septal defect is a very rare congenital cardiac anomaly, especially in combination with aortic arch interruption. It is always challenging to choose the optimal treatment tactics for such patients. One of the possible types of intervention is the Yasui procedure. There are only 19 reported cases in the literature of aortic atresia with interruption of the aortic arch type B or C, and not a single clinical case of type A.

Case presentation

The proband was a 2-day-old boy with diagnosis: aortic atresia with a ventricular septal defect and interruption of the aortic arch type B. The child underwent a Yasui procedure without serious postoperative complications and with good long-term result.

Conclusions

The Yasui procedure in patients with aortic atresia and interrupted aortic arch can be performed with minimal complications, even in low-weight patients.
Short-cut route validated for monitoring fentanyl and its metabolite in urine using LC–MS/MS, in a wide concentration range
Authors: Cavus Yonar Fatma , Anılanmert Beril , Acikkol Munevver
Published: July 2024

Background

Fentanyl is a highly potent analgesic, used in surgery, frequently abused or used in drug-facilitated crimes (DFC) and in military activities. It is also increasingly used in the treatment of chronic pain (especially in cancer patients). The improper use of transdermal patch forms can cause toxicity and deaths, related to overdose or combined use with other drug substances. Methods are needed for fast, reliable and inexpensive fentanyl detection and we aimed to develop such a method in urine using LC–MS/MS, especially for toxic and fatal concentrations which lack in the literature.

Results

An LC–MS/MS method has been presented for the co-determination of fentanyl and its main metabolite, norfentanyl in urine. The recoveries of the extraction method were 95(± 6)% and 70(± 9)% for fentanyl and norfentanyl, respectively. LOD and LOQ values are 1.7 and 14.0 ng/mL for fentanyl, while they were 20.6 ng/mL and 42.0 ng/mL for norfentanyl.

Conclusion

A rapid, sensitive, very practical, inexpensive and a high-recovery analysis method is developed and validated. This is the only fentanyl monitoring LC–MS/MS method in urine having a linearity over a wide range up to 500.0 ng/mL and its success is demonstrated on real samples in the therapeutic drug monitoring of fentanyl and is expected to contribute to clarify intoxications/deaths related to its use.

Graphical Abstract
Multi-objective parametric optimization process of hybrid reinforced titanium metal matrix composite through Taguchi-Grey relation analysis (TGRA)
Authors: Gemeda Birhane Assefa , Sinha Devendra Kumar , Mengesha Getinet Asrat , Gautam Satyam Shivam
Published: July 2024

Hybrid titanium metal matrix composites (HTMMCs) are advanced composite materials that can be tailored to a variety of applications. Because of their decreased fuel consumption and cost, they are popular in the transportation industry. Using multi-objective optimization and Taguchi-based Grey relational analysis (TGRA), this study investigates the impact of hybrid reinforced HTMMCs synthesized using powder metallurgy on their physic mechanical properties. The research investigates reinforcements such as B4C, SiC, ZrO2, and MoS2 at various compaction pressures, milling durations, and sintering temperatures. The best powder metallurgy control parameters for HTMMC synthesis, with a milling time of 5 h, a compaction pressure of 40 MPa, a sintering temperature of 1200 °C, and a sintering time of 1 h, and a compaction time of 40 min. According to validation results, HTMMC material with optimized process parameters had experimental densities, porosities, hardness, compressive strength, and wear rates of 4.29 gm/cm3, 0.1178%, 71.53RHN, 2782.36 MPa, and 0.1519 mm3 correspondingly. The material hardness was increased by 1.99% and compressive strength by 2.87%. The use of Taguchi and GRA techniques strongly verified that the impact of milling duration and sintering temperature was the greatest of all five factors. The novel synthesized hybrid reinforcing HTMMCs outperformed pure Ti grade 5 and single and double fortified HTMMCs in terms of physic mechanical characteristics. As a result, the newly developed tetra hybrid reinforced HTMMC material is expected to be used in heavy-duty vehicles, aerospace, automobiles, maritime, and other industries.