bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic trajectories of families with rare diseases in Chile from the perspectives of patients, carers, and healthcare workers: a qualitative study
Authors: Cabieses Báltica , Obach Alexandra , Roberts Antonia , Repetto Gabriela 
Published: February 2025

Abstract

Background
Rare diseases are conditions that have a low prevalence in the population and a high disease burden and are often chronic and progressive. International evidence concerning the experience of people and families living with rare diseases is scarce, leading to late and erroneous diagnoses, as well as non-specific treatments. This study explored the therapeutic trajectories of people and families living with rare diseases within Chile’s public and private healthcare systems from the perspective of patients, caregivers, and medical teams, including the initial symptoms, first consultation, testing, diagnosis, treatment, and follow-up.

Methods
A qualitative exploratory study was conducted through multiple case studies. Sixty participants were interviewed in person and/or virtually: patients (n = 16), caregivers (n = 22), healthcare workers (n = 20), and two patient organisation leaders. The material was analysed using thematic analysis. The project was approved by the Scientific Ethics Committee of Facultad de Medicina Clínica Alemana, Universidad del Desarrollo.

Results
After similar initial symptoms and first consultation, three main types of trajectories were identified: (i) the path taken by those who reach a diagnosis for a disease that has specific treatment available; (ii) the journey of those who reach a diagnosis for their health condition, but their disease does not have a specific treatment available; and (iii) the trajectory of those who have not reached a diagnosis and receive symptomatic treatments for symptoms.

Conclusions
The therapeutic trajectories of patients with rare symptoms are similar in terms of initial symptoms and first consultation. However, their paths diverge at the diagnostic stage, with diverse experiences related to these journeys, largely based on having a diagnosis and whether there is a specific treatment. Rare conditions in Chile requires further attention and urgent action that considers those who live with them and their families.
Genome-wide CRISPR screening identifies PHF8 as an effective therapeutic target for KRAS- or BRAF-mutant colorectal cancers
Authors: Liu Zhao , Li Yiqi , Wang Simeng , Wang Yubo , Sui Mengjun , Liu Jiaxin , Chen Pu , Wang Jianling , Zhang Yuchen , Dang Chengxue , Hou Peng 
Published: February 2025

Abstract

Background
Mutations in KRAS and BRAF genes are prevalent in colorectal cancer (CRC), which strikingly promote tumorigenesis and lead to poor response to a variety of treatments including immunotherapy by activating the MAPK/ERK pathway. Thus, there is an urgent need to discover effective therapeutic targets and strategies.

Methods
CRISPR-Cas9 lentiviral knockout library was used to screen the suppressors of anti-PD1 immunotherapy. Bioinformatic analysis was used to analyze the correlation between PHF8 expression and immune indicators in CRC. In vitro and in vivo experiments were utilized to determine the effects of PHF8 on the immune indexes and malignant phenotypes of CRC cells. qRT-PCR, western blotting, immunohistochemical (IHC) staining, and chromatin immunoprecipitation (ChIP)-qPCR assays were used to determine the regulatory effects of PHF8 on PD-L1, KRAS, BRAF, and c-Myc and the regulatory effect c-Myc/miR-22-3p signaling axis on PHF8 expression in CRC cells.

Results
This study identified histone lysine demethylase PHF8 as a negative regulator for the efficacy of anti-PD1 therapy and found that it was highly expressed in CRCs and strongly associated with poor patient survival. Functional studies showed that PHF8 played an oncogenic role in KRAS- or BRAF-mutant CRC cells, but not in wild-type ones. Mechanistically, PHF8 up-regulated the expression of PD-L1, KRAS, BRAF, and c-Myc by increasing the levels of transcriptional activation marks H3K4me3 and H3K27ac and decreasing the levels of transcriptional repression mark H3K9me2 within their promoter regions, promoting immune escape and tumor progression. Besides, our data also demonstrated that PHF8 was up-regulated by the c-Myc/miR-22-3p signaling axis to form a positive feedback loop. Targeting PHF8 substantially improved the efficacy of anti-PD1 therapy and inhibited the malignant phenotypes of KRAS- or BRAF-mutant CRC cells.

Conclusion
Our data demonstrate that PHF8 may be an effective therapeutic target for KRAS- or BRAF-mutant CRCs.
Altered synaptic homeostasis: a key factor in the pathophysiology of depression
Authors: Wang Bokai , He Teng , Qiu Guofan , Li Chong , Xue Song , Zheng Yuanjia , Wang Taiyi , Xia Yucen , Yao Lin , Yan Jinglan , Chen Yongjun 
Published: February 2025

Abstract
Depression, a widespread psychiatric disorder, is characterized by a diverse array of symptoms such as melancholic mood and anhedonia, imposing a significant burden on both society and individuals. Despite extensive research into the neurobiological foundations of depression, a complete understanding of its complex mechanisms is yet to be attained, and targeted therapeutic interventions remain under development. Synaptic homeostasis, a compensatory feedback mechanism, involves neurons adjusting synaptic strength by regulating pre- or postsynaptic processes. Recent advancements in depression research reveal a crucial association between the disorder and disruptions in synaptic homeostasis within neural regions and circuits pivotal for emotional and cognitive functions. This paper explores the mechanisms governing synaptic homeostasis in depression, focusing on the role of ion channels, the regulation of presynaptic neurotransmitter release, synaptic scaling processes, and essential signaling molecules. By mapping new pathways in the study of synaptic homeostasis as it pertains to depression, this research aims to provide valuable insights for identifying novel therapeutic targets for more effective antidepressant treatments.
Between intention and action: the paradoxes of female vaccination
Authors: Santos-Requejo Libia , Torres-González Obdulia María 
Published: February 2025

Abstract

Background
The article addresses two paradoxes related to the vaccination of women in the context of the COVID-19 pandemic. The first paradox lies in the fact that, though women tend to be more concerned about health issues, they declare less of an intention to vaccinate than do men. The second paradox is that, despite reporting less intention to vaccinate, women actually take up vaccines more than men. This article sets out to study the reasons for these paradoxes.

Methods
We used information from a representative sample of the Spanish population. A dichotomous variable was created (‘change’ versus ‘consistency’, in relation to respondents’ intention and final decision to get vaccinated), and two logistic regression models were applied: one for the group of women and the other for the group of men.

Results
Several factors have been identified as influencing the change of opinion: such as trust in the health system, conspiracy beliefs about vaccines, positive evaluation of science and technology, level of knowledge, ideology and religion. It is noteworthy that several differences are found between men and women in terms of the factors causing them to change their opinion about vaccination.

Conclusions
The most relevant conclusion is that intention studies in the field of vaccination lose predictive power in the case of women’s vaccination. It should also be noted that, with women, there are no factors that conclusively explain their change of opinion. Therefore, if the factors influencing vaccination behaviour are to be discovered, it is necessary to modify the questions included in the questionnaires in order to find the variables that explain women’s behaviour.
Variation of Mg isotopes during mineral dissolution at pH = 1 and T = 25 °C: Part 2. Olivine and pyroxene
Authors: Ryu Jong-Sik 
Published: February 2025

Abstract

Background
The high reactivity of mafic minerals, such as olivine and pyroxene, plays a crucial role in controlling the global magnesium (Mg) flux and its isotopic composition. This study investigates the mechanisms and extent of Mg isotope fractionation during the dissolution of these minerals under far–from–equilibrium conditions. These findings provide valuable insights into the behavior of Mg isotopes in natural environments and their potential as a geochemical proxy for understanding Earth's carbon cycle.

Methods
Mafic minerals (olivine, enstatite, and diopside) with particle sizes ranging from 63 to 245 µm were subjected to dissolution experiments in a plug–flow reactor under far–from–equilibrium conditions. Effluent solutions were collected over a period of 1872 h. Elemental concentrations were determined using a Inductively Coupled Plasma Optical Emission Spectroscopy (ICP–OES), while Mg isotopic compositions were analyzed using Multi–Collector Inductively Coupled Plasma Mass Spectrometry (MC–ICP–MS).

Results
Elemental concentrations displayed distinct temporal trends for olivine and pyroxene. Olivine dissolution demonstrated a gradual increase in elemental concentrations during the initial 20 h, followed by a subsequent decline towards baseline levels. In contrast, pyroxene dissolution exhibited a rapid initial release of elements within the first 4 h, followed by an abrupt decrease towards near-zero concentrations. Olivine dissolution exhibited pronounced oscillations in δ2⁶Mg values, ranging from − 0.53‰ to − 0.21‰. Conversely, pyroxene dissolution (enstatite and diopside) displayed more gradual trends, with δ2⁶Mg values ranging from − 0.41‰ to − 0.26‰ for enstatite and from − 0.43‰ to − 0.21‰ for diopside.

Conclusions
The output solutions exhibited an initial period of rapid, incongruent mineral dissolution, followed by a sharp decline towards near–zero rates. The observed δ2⁶Mg variations between solution and mineral, ranging from − 0.43‰ to + 0.18‰, suggest that these shifts are likely influenced by either differences in their crystal structures or the formation of secondary phases. This finding highlights the significant influence of mafic minerals, with their high reactivity compared to other silicate minerals, on the Mg flux and isotopic compositions in terrestrial waters draining basalts and the ocean.
The burden of visually diagnosed female genital schistosomiasis among women with infertility in the Volta Region of Ghana
Authors: Orish Verner N. , Kaba Gladys , Dah Anthony K. , Maalman Raymond S. , Amoh Micheal , Appiah-Kubi Adu , Azanu Wisdom , Adzah David , Nyonator William R. , Kumi Micheal B. , Awutey-Hinidza Diana S. , Atachie Irene , Ahiaku Portia , Kwadzokpui Precious K. , Fatau Adam A. , Smith-Togobo Cecila , Yong Tai-Soon , Cho Young-soon , Morhe Emmanuel S. K. , Kim So Yoon , Gyapong Margaret 
Published: February 2025

Abstract

Background
Female genital schistosomiasis (FGS) is the outcome of the deposition of Schistosoma haematobium egg in the ovaries, fallopian tubes, uterus or cervix of women in schistosomiasis endemic areas. Chronic and untreated FGS can result in an increased risk of human immunodeficiency virus (HIV) acquisition and infertility. This study aimed to evaluate the burden of visual FGS among women with infertility in the Volta region of Ghana.

Methods
This study was a comparative cross-sectional study involving women with infertility defined as women with inability to achieve pregnancy after 12 months or more of frequent (3–4 times a week) unprotected sexual intercourse and nursing mothers (fertile women) from selected districts in the Volta Region. Questionnaire administration was used to obtain sociodemographic information including recent and childhood contact with water bodies as well as the practice of open defecation and clinical information such as the presence of genital symptoms. Urine samples were collected for detection of eggs of S. haematobium, and the women’s lower genital tracts were examined using a handheld colposcope by two gynecologists and a third to resolve discrepancies. Data were analyzed using SPSS version 23 with frequency distribution done for the sociodemographic variables and the prevalence of FGS in the women. Pearson Chi-square analysis was performed to find any significant difference between the prevalence of FGS among infertile and fertile women and any significant association between any socioeconomic and clinical variables with FGS. Logistics regression analysis was performed to investigate sociodemographic and other risk factors for FGS among women.

Results
Of the 265 sampled women 132 (49.8%) were infertile and 133 (50.2%) were nursing mothers (fertile women). More women had visual FGS (155, 58.5%) and most with FGS were fertile [96, 76.1%; infertile, 59(45.3%); p < 0.001], with infertile women having lower odds of FGS in this study (AOR, 0.29 [95% CI 0.17–0.50]; p < 0.001); adjusted for childhood and current contact with rivers and streams, availability of toilets facility, practice of open defecation and age. More women with FGS had childhood contact with rivers and streams (68.4%, p = 0.007) with lower odds of FGS seen in women without childhood contact with rivers and streams (AOR, 0.52 [95% CI 0.31–0.88]; p = 0.015).

Conclusion
In this study, infertile women unexpectedly had lower odds of FGS suggesting the need for more rigorous research on this topic to elucidate the true contribution of FGS on infertility.
Integrating green HRM for productivity and sustainability: green innovation, engagement and pro-environmental behavior as key mediators
Authors: Islam Mohammad Fakhrul , Al Masud Abdullah , Emon Md. , Shuvro Razuan Ahmed , Jony Mohammad Toriqul Islam , Akter Tania 
Published: February 2025

Abstract
This study examines how employee engagement functions as a mediator between worker productivity and Green Human Resource Management (GHRM) practices in Bangladesh's industrial industry. We used a web-based, structured questionnaire to survey 401 workers from different companies. Comprehensive research using structural equation modeling showed that GHRM significantly improves employee engagement (p < 0.05, β = 0.154), which in turn boosts worker productivity (β = 0.281). Additionally, the association between GHRM and productivity is significantly mediated by employee engagement (p < 0.05), suggesting that engaged employees are more productive in companies that implement GHRM practices. This study emphasizes the usefulness of implementing GHRM practices for manufacturing managers in order to cultivate a motivated and effective workforce. Using the Ability, Motivation, and Opportunity (A-M-O) Theory, this study offers insights applicable to comparable situations around the world and advances our understanding of how sustainable HR practices can address issues in a Bangladeshi manufacturing sector.

Graphical abstract
Impact of introducing a capacity-based mental health law in Norway: qualitative exploration of multi-stakeholder perspectives
Authors: Jorem Jacob , Førde Reidun , Husum Tonje Lossius , Dahlberg Jørgen , Pedersen Reidar 
Published: February 2025

Background
Decision-making capacity (DMC) is key to capacity-based mental health laws. In 2017, Norway introduced a lack of DMC as an additional criterion for involuntary care and treatment to strengthen patient autonomy and reduce involuntary care. Health registry data reveal an initial reduction followed by rising involuntary care and treatment rates post-2017. Despite jurisdictions moving towards capacity-based mental health laws, little is known about their impact.

Aims
To explore the impact of introducing a capacity-based mental health law governing involuntary care and treatment.

Method
Semi-structured interviews and focus groups were conducted in 2018 with 60 purposively sampled stakeholders, including patients, families, health professionals and lawyers. Of these, 26 participated in individual follow-up interviews in 2022–23. The transcribed interviews were thematically analysed following Braun and Clarke.

Results
Four themes emerged: (a) increased awareness of patient autonomy and improved patient involvement; (b) altered thresholds for involuntary admission and discharge and more challenging to help certain patient groups; (c) more responsibility for primary health services; and (d) increased family responsibility but unchanged involvement by health services.

Conclusions
Introducing a capacity-based mental health law appears to raise awareness of patient autonomy, but its impact depends on an interplay of complex health, social and legal systems. Post-2017 changes, including rising involuntary care and treatment rates, higher thresholds for admissions and increased pressure on primary health services and families, may be influenced by several factors. These include implementation of decision-making capacity, legal interpretations, formal measures for care of non-resistant incompetent individuals, reduced in-patient bed availability, inadequate voluntary treatment options and societal developments. Further research is needed to better understand these changes and their causes.
A pilot study of a ketogenic diet in bipolar disorder: clinical, metabolic and magnetic resonance spectroscopy findings
Authors: Campbell Iain H. , Needham Nicole , Grossi Helen , Kamenska Ivana , Luz Saturnino , Sheehan Shane , Thompson Gerard , Thrippleton Michael J. , Gibbs Melissa C. , Leitao Joana , Moses Tessa , Burgess Karl , Rigby Benjamin P. , Simpson Sharon A. , McIntosh Emma , Brown Rachel , Meadowcroft Ben , Creasy Frances , Mitchell-Grigorjeva Maja , Norrie John , McLellan Ailsa , Fisher Cheryl , Zieliński Tomasz , Gaggioni Giulia , Campbell Harry , Smith Daniel J. 
Published: February 2025

Background
Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
Identifying redundant singularity in Padé approximant
Authors: Chang Fu-Ming , Liu Yuan-Yuan , Gu Xin , Li Wen-Du , Dai Wu-Sheng 
Published: February 2025

Abstract
The Padé approximant performs the pole analysis in statistical mechanics and particle physics. The Padé approximant can recover the singularity information lost in the polynomial approximation given by perturbation methods but also introduces redundant singularities. This paper presents a method to identify redundant singularities by analyzing the approximation itself rather than relying on the original function or underlying physical principles.
Association of Maternal Thyroglobulin Antibody with Preterm Birth in Euthyroid Women
Authors: Yang Shuai , Huang Zixuan , Zhang Yong , Li Yanan , Zhou Yulai , Guan Haixia , Fan Jianxia 
Published: February 2025

Abstract

Context
While the association between maternal thyroid peroxidase antibody (TPOAb) positivity and preterm birth (PTB) risk has been established, the association between thyroglobulin antibody (TgAb) and PTB remains unclear.

Objective
This study aimed to explore the association between TgAb and PTB risk in euthyroid women.

Methods
This single-center, prospective cohort study enrolled euthyroid women in the first trimester. Data on serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TgAb, and TPOAb was collected. Participants were categorized into two groups (TgAb-negative and TgAb-positive). PTB was subtyped into spontaneous PTB (S-PTB) and medically-induced PTB (MI-PTB); and into early PTB (E-PTB) and late PTB (L-PTB). Logistic regression models examined the associations between TgAb and PTB and its subtypes, with stratification by first-trimester TSH levels (0.1-2.5 mIU/L, 2.5-4.0 mIU/L).

Results
This study comprised of 58,247 euthyroid pregnant women. Adjusting for confounders, TgAb positivity was associated with a 16% increased risk of PTB (adjusted odds ratio (aOR) 1.16, 95% confidence interval (CI) 1.03-1.29, P=0.01) compared to the TgAb-negative group. Specifically, TgAb positivity showed higher risk of S-PTB and L-PTB, aOR 1.22 (95% CI 1.06, 1.39) and aOR 1.17 (95%CI 1.04, 1.32), respectively. Consistent results were observed when analyzing TgAb concentration as a continuous variable. TSH stratification analysis revealed that these associations were significant only among women with TSH levels between 0.1-2.5 mIU/L.

Conclusions
In euthyroid women, TgAb positivity was associated with higher risk of PTB that mainly manifested as S-PTB and L-PTB. However, the clinical significance of these findings is limited.
A case for subnational nutrition financing: The development and use of county-level investment cases in Kenya
Authors: Jain Sakshi , Ahsan Sameen , Walters Dylan David , Kinyua Geoffrey , Smith Johniere , Nyagaya Martha , Greig Alison , Arabi Mandana 
Published: February 2025

This paper aims to emphasize the significance of creating subnational nutrition action plans in regions with high variation in nutrition challenges and evaluates their projected return on investment in Kenya. Despite steady progress, undernutrition in Kenya remains high, costing the country an estimated US$ 4.2 billion or 7% of its GDP annually. Under Kenya’s decentralized government system, numerous counties developed sectoral County Nutrition Action Plans (CNAPs) in 2018 to identify and prioritize essential nutrition actions to target undernutrition at the subnational level. In this paper, the authors present findings from county investment cases (CICs) in five counties — Nandi, Busia, Makueni, Vihiga, and Elgeyo Marakwet—including the costs, health impacts, and benefit to cost ratios of implementing high-impact nutrition interventions. Data was collected on the target coverage and cost of interventions prioritized in each county’s CNAPs for the 2018 to 2022 period. A monetized DALY approach, using the value of a statistical life methodology was used for cost-benefit analysis and the Optima Nutrition tool was used for cost-effectiveness analysis. The estimated cumulative impact of the five CNAPs was projected as 1,800 child and 115 maternal deaths averted; preventing and treating 19,000 cases of stunting and 4,700 cases of wasting in children under five and averting 67,000 cases of anaemia in pregnant women and adolescent girls. The county-level benefit-cost ratios range from $5:1 to $14:1 (at a default 3% discount rate). This analysis demonstrates that localized subnational plans can be advantageous for policymaking and prioritization to better address subnational disparities in undernutrition and offer a high return on investment.