bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating neurofilament light chain serum levels as a diagnostic marker for Lyme neuroborreliosis
Authors: Hirzel Cédric , Grütter Annina , Grandgirard Denis , Hoepner Robert , Suter-Riniker Franziska , Leib Stephen L.
Published: January 2025

Background:

Serum neurofilament light chain (sNfL) is a biomarker for neuro-axonal injury.

Objectives:

To assess sNfL’s utility as a diagnostic marker for Lyme neuroborreliosis (LNB).

Methods:

We compared serum and CSF NfL levels in LNB patients and age-matched controls. Age-adjusted NfL values were used in receiver operating characteristic (ROC) analysis.

Design:

Retrospective cohort study.

Results:

Eighty-six patients (30 LNB, 29 with-, and 27 without neurological disorders) were included. Compared to individuals without neurological disease, LNB patients showed increased serum (median (interquartile range, IQR): 36.3 pg/ml (19.3–112.0) vs 20 pg/ml (12.9–37.3), p < 0.001) and CSF NfL levels (median (IQR): 1000.0 pg/ml (286.0–6471.0) vs 182 pg/ml (99.3–474.0), p < 0.001). NfL concentrations were similar in LNB and other neurological disorders. ROC analysis of age-adjusted sNfL and CSF NfL levels showed areas under the curve of 0.78 (95% confidence interval (CI): 0.66–0.89) and 0.83 (95% CI: 0.71–0.94), respectively.

Conclusion:

sNfL concentrations lack sufficient diagnostic capability for LNB diagnosis.
Contending With Sexual Temptation: Theological Divergence Between the Desert Mothers and Fathers
Authors: Cash Emily M. H.
Published: January 2025

Much of the lasting spiritual fruit of early Christian monasticism was born in the desert, but use of the desert tradition for spiritual formation should be conscious of its potential theological liabilities. Hence, this paper explores gendered dimensions of early ascetic literature, particularly the Desert Fathers and Mothers’ divergent approaches to sexual temptation. The Fathers exhibit an avoidant posture toward women, projecting their sexual temptations onto female bodies and visualizing demonic activity in female form. This projection reflects broader cultural associations of women with lust and carnality, which reinforces misogyny and validates violence. In contrast, the Desert Mothers internalize responsibility for sexual temptation, emphasizing personal accountability and spiritual disciplines such as discernment, prayer, and embodied relationality rather than violent abjection. Attention to this gendered divergence thus has the potential to not only interrupt unintentional perpetuation of misogynist theology, but to resource modern ascetic practice for both genders.
Prevalence of gastrointestinal symptoms after recovery from COVID-19: A questionnaire-based study in the Aseer region
Authors: Alzahrani Mohammed Attieh , Altalhiyyah Khalid Siraj , Albariqi Mohammed Mousa , Alkhayri Meshal Ali , Alshahrani Saad Ali , Alnasser Sultan Saad , Alshehri Nawaf Mohammed , Alqahtani Saad Haif , Alqahtani Saud Haif
Published: January 2025

Background:

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide, and although it is primarily a respiratory illness, gastrointestinal symptoms have been reported in a significant proportion of patients.

Aim:

Prevalence of gastrointestinal symptoms after recovery from COVID-19.

Methodology:

A community-based cross-sectional study was conducted in the Aseer region of Saudi Arabia. The study population included individuals aged 18 years or older with COVID-19 and living in the Aseer region. The data were collected through a pretested, structured online questionnaire preceded by consent and were used to maintain the confidentiality of the data. The questionnaire covered participants’ data, COVID-19 infection status, and gastrointestinal tract symptoms during and after recovery from the infection.

Results:

A total of 409 participants in the Aseer region completed the study survey. The participants’ ages ranged from 18 to more than 50 years, with a mean age of 34.5 ± 11.9 years. A total of 205 (50.1%) participants were females. A total of 263 (64.3%) of the study participants experienced gastrointestinal tract symptoms during COVID-19 infection. Additionally, 203 (49.6%) of the study participants had gastrointestinal tract symptoms after recovering from COVID-19 infection. The most commonly reported symptoms were diarrhea (13.2%), nausea (13.2%), anorexia (12.7%), abdominal pain (11%), and constipation. Male sex who suffered form severe COVID-19 infection, and gastrointestinal tract symptoms during acute infection were significantly associated with post-COVID-19 gastrointestinal tract symptoms ( p < 0.05).

Conclusions:

In conclusion, the current study showed that nearly two-thirds of active COVID-19 patients experienced gastrointestinal tract symptoms. Additionally, approximately half of the COVID-19 patients who recovered had gastrointestinal tract-related symptoms, but few of those patients had gastrointestinal tract-related symptoms within 1 week.
Comparison of health technology assessments for digital therapeutics in Germany, the United Kingdom and France
Authors: Arcà Emanuele , Heldt Dorothea , Smith Martina
Published: January 2025

Objective

Digital therapeutics (DTx) are promising technologies. However, current assessment and access frameworks, when they exist, are heterogeneous and fragmented. We analysed and compared health technology assessment (HTA) criteria for DTx across European countries that had assessed the same DTx products. This allowed us to conduct a direct comparison of these countries’ DTx assessment frameworks.

Methods

A scoping review identified HTA DTx documents from European HTA bodies with specific DTx frameworks in place. The HTAs of the same DTx products assessed across multiple countries were then extracted and analysed.

Results

Deprexis and Velibra were the only DTx products assessed by multiple countries: Deprexis, indicated for depression, was assessed by Germany, the United Kingdom (UK) and France; and Velibra, indicated for anxiety, was assessed by Germany and the UK. There are notable differences among those frameworks, but what they share is an emphasis on the context-specific positioning of products within the disease landscape, choice of comparators and usage and usability data. Safety data are not a major focus in DTx assessments in these countries, but a request is often made for the addition and evaluation of risk-flagging systems.

Conclusion

The majority of European countries do not have a specific framework in place for the assessment of DTx, and major differences exist among recently implemented frameworks. The current policy landscape at the European Union level offers an opportunity to establish a harmonized framework for the assessment of DTx and possibly faster access and integration of such promising technologies.
The engagement of healthcare providers in implementing the selfBACK randomised controlled trial – A mixed-methods process evaluation
Authors: Stochkendahl Mette Jensen , Nicholl Barbara I , Wood Karen , Mair Frances S , Mork Paul Jarle , Søgaard Karen , Rasmussen Charlotte DN
Published: January 2025

Background

People with low back pain (LBP) are often recommended to self-manage their condition, but it can be challenging without support. Digital health interventions (DHIs) have shown promise in supporting self-management of LBP, but little is known about healthcare providers’ (HCPs) engagement in implementing these.

Aims

We aimed to examine HCPs’ engagement in patient recruitment for the selfBACK app clinical trial and explore their perceptions of the app.

Methods

In a mixed-methods design, we conducted a process evaluation alongside the selfBACK trial, triangulating quantitative data from trial recruitment logs and a vignette-based survey, and qualitative data from trial procedure documents, interviews with HCPs, and survey free-text responses. From 2019 to 2020, we recruited 57 HCPs from Norway and 39 health clinics in Denmark and collected quantitative and qualitative data in parallel. Results were integrated using displays.

Results

Overall, 825 patients were recruited by the HCPs. The vignette-based survey showed high agreement among HCPs (n = 62) with the self-management plans generated by the app (84.1–88.9%) but also highlighted concerns about tailoring and content. Interviews with HCPs (n = 19) revealed challenges with recruitment due to busy schedules, competing tasks, and varying levels of interest and engagement in the study.

Conclusions

The study identified factors that impact HCPs’ engagement in recruiting patients for the selfBACK trial and highlighted overall positive views of the selfBACK app, although some concerns about the content and tailoring of the app were raised. Understanding HCP motivations and workload is crucial for the successful implementation of DHIs in clinical practice.
Embracing Change in the Modern Working Environment: Exploring the Role of Trust, Experimentation, and Adaptability in the Acceptance of New Technologies
Authors: Gößwein Eva , Liebherr Magnus
Published: January 2025

In a working environment facing increasing digitalization and the Fourth Industrial Revolution, the acceptance of new technologies remains an important factor. Based on the Technology Acceptance Model (TAM) and the Artificial Intelligence Acceptance Model (AIAM), this study examines if individual adaptability, trust in technology, as well as openness and willingness to experiment influence technology acceptance in the working environment. Using an online questionnaire approach, a sample of N = 769 participants ( M = 51.25, SD = 13.88 years; 390 female) was recruited to test the theoretically derived model with structural equation modeling. Results suggest including trust in technologies in future technology acceptance models in the working environment. Furthermore, the TAM-variable perceived ease of use was not a significant predictor, which is discussed in detail. Regarding the antecedents derived from AIAM, individual adaptability proves to be relevant, while first insights on the non-significant influence of openness to experiment are gained. The final model explains more than two-thirds of the intention to use new technology and thus provides an important contribution to understanding the acceptance of new technologies in a working environment.
Sexual Dysfunction in Cervical Spondylomyelopathy and Its Prognosis Following Surgical Decompression: A Systematic Review
Authors: Viswanathan Vibhu Krishnan , Muthu Sathish
Published: January 2025

Study Design

Systematic review.

Objective

While the occurrence of sexual dysfunction in patients sustaining traumatic cervical or thoracic injuries is well acknowledged, the evidence regarding its prevalence and outcome in individuals with degenerative cervical myelopathy (DCM) is still limited. The current systematic review was planned to comprehensively evaluate the existing literature regarding the prevalence, patterns, presentation, and outcome of sexual dysfunction in patients presenting with DCM.

Methods

A thorough search of the literature was performed on October 15, 2024, using 5 different databases (Google Scholar, Embase, PubMed, Web of Science and Cochrane Library). Studies on sexual dysfunction in DCM published until 2024 were scrutinized. Narrative or systematic reviews, opinions, letters to the editor, and manuscripts published in non-English languages were excluded.

Results

Overall, the literature search yielded a total of 384 articles of which 7 articles with 910 patients were included in the analysis. The overall prevalence of erectile dysfunction (ED) in CSM ranges between 3 and 6%. 82% of patients with preoperative ED had an abnormal psychogenic erection while the remaining had an abnormal reflexogenic erectile function. The erectile function was reported to improve substantially following decompressive surgery (68% recovery rate; P = 0.05). The presence of preoperative sexual dysfunction has been associated with poorer neurological outcomes (50% recovery rate; including poorer gait recovery). The data regarding ejaculatory disturbances and female sexual dysfunction in DCM patients are still limited.

Conclusion

ED occurs in 3 to 6% of patients with DCM, with a majority of patients suffering from ED from psychogenic origin. Surgical decompression can significantly improve the sexual recovery in these patients. Patients with ED have overall poorer neurological recovery.
Chinese Translation and Validation of the Oslo Sports Trauma Research Center Questionnaires on Overuse Injuries and Health Problems
Authors: Lu Yi , Chiu Joe Chih-Hao , Chen Alvin C. , Hsu Kuo-Yao , Chan Yi-Sheng , Zhang En-Chong , Sheu Huan
Published: January 2025

Background:

The importance of monitoring both physical and mental health in athletes across different levels of sport is increasingly acknowledged due to potential injury risks. However, for the Chinese-speaking population, there has not yet been an appropriate assessment tool available.

Purpose:

To translate, culturally adapt, and assess the validity and reliability of the Chinese versions of the updated Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC-O2) and the Health Problems Questionnaire (OSTRC-H2) among Taiwanese collegiate athletes.

Study Design:

Cohort study (diagnosis); Level of evidence: 3.

Methods:

The OSTRC-O2 and OSTRC-H2 questionnaires were translated from English to Chinese following international guidelines. Subsequently, 80 and 84 collegiate athletes, respectively, were invited to complete these questionnaires on a weekly basis for 8 weeks. Internal consistency was evaluated using Cronbach alpha coefficient, while test-retest reliability was assessed with the intraclass correlation coefficient (ICC). Severity scores from the questionnaires were also documented.

Results:

High response rates of 90% (n = 72/80) and 90.5% (n = 76/84) were achieved in the OSTRC-O2.CH and OSTRC-H2.CH groups, respectively, demonstrating strong acceptance among athletes, with no significant issues in back-translation. High content validity was observed across the different body parts in the translated OSTRC-O2, with Cronbach alpha values of .82, .83, .82, and .83 for the knee, shoulder, elbow, and lower back, respectively. The translated OSTRC-H2 also showed excellent internal consistency, with a Cronbach alpha of .95. The ICC values for test-retest reliability were 0.88, 0.82, 0.92, and 0.92 for the knee, shoulder, elbow, and lower back in the OSTRC-O2, and the ICC for the OSTRC-H2 was 0.90, indicating very good reliability for both questionnaires.

Conclusion:

The Chinese versions of the OSTRC questionnaires were found to be valid and reliable for monitoring overuse injuries and health issues among Chinese-speaking collegiate athletes.
Behavioral Medicine Can Tackle Cardiovascular Disease Risk and Burden: A Call for New Priorities
Authors: Burg Matthew M. , Stewart Jesse C. , Gaffey Allison E. , Särnholm Josefin , Vela Alyssa M. , Kovacs Richard J.
Published: January 2025

Cardiovascular disease (CVD) remains the number one cause of death in the US. Annual costs of CVD are estimated at $600 billion annually, and projected to top $1.1 trillion by 2035. Modifiable behavior and psychosocial factors contribute more than 50% to CVD risk, prognosis, and health-related quality of life. Leading cardiology professional groups have called for attention to these factors as part of prevention and treatment of CVD, yet the integration of behavioral and psychosocial health as part of overall CV care remains to be realized. The field of cardiovascular behavioral medicine could address this evidence-to-implementation gap; policy implications for changes in research, training and healthcare will be required.
Cultivation of Grit in Nursing Students: A Qualitative Descriptive Study “Cultivation of Grit”
Authors: Muchna Carolyn Spriggs
Published: January 2025

Background

Predicted nursing deficits and low nursing student retention rates highlighted the need to investigate cultivation of grit, a malleable trait involving perseverance and passion to achieve long-term goals amidst challenges and difficulties.

Objective

The objective of this study was to identify how cultivation of grit and additional academic and non-academic strategies aided gritty second-year associate degree-seeking nursing students in addressing nursing program challenges and completing their nursing program.

Methods

Twenty-two second-year associate degree-seeking nursing students in rural central Arizona completed demographic and Grit-O Scale questions using Survey Monkey™ and participated in semi-structured interviews or focus group discussions held from September through December 2022. Research questions provided study foundation: RQ1: How do second-year nursing students with high levels of self-perceived grit of greater than 3.5 out of 5 as measured on the Grit-O Scale describe how grit was cultivated during their associate degree-seeking nursing program? RQ2: How do second-year nursing students with high levels of self-perceived grit describe how additional academic and non-academic strategies added to them in dealing with the challenges of their associate degree-seeking nursing program?

Design

Qualitative Descriptive Research

Results

Inductive thematic analysis revealed six themes: importance of perseverance and passion, facets of grit; identification of program challenges and strategies used to deal with challenges; and the significance of support from nursing cohort, family, and friends, and nursing instructors.

Conclusions

Effective strategies for participating nursing student retention and program completion involved cultivation of grit and its facets of perseverance and passion and additional academic and non-academic strategies of nursing cohort and instructor support aided students in dealing with challenges faced during their associate degree-seeking nursing program at a rural, central Arizonan community college.
The co-constitution of chaos: The entangling of individual and institution in the Australian criminal justice system
Authors: Morgan Patricia , Hwang Ye In (Jane) , Butler Tony , Simpson Paul , Schofield Peter W
Published: January 2025

Justice-involved individuals convicted of crimes involving violence are often depicted as chaotic, whereas the chaos they encounter in criminal justice institutions is not commonly reported. Nonetheless, we found that chaos can be co-constituted at points where justice-involved individuals and justice institutions intersect. Our findings are drawn from qualitative research on a pharmacotherapy trial designed to reduce violence: Reducing impulsivity in repeat violent offenders using a selective serotonin reuptake inhibitor, ReINVEST. Data were analysed using a grounded inductive approach and we drew on Law and Lock and Nguyen's innovative theories of “mess” and “entanglement” respectively. Analysis and theoretical explication revealed themes of entanglement, conflicting justice cultures, unacknowledged dysfunction in justice institutions, and negative impacts of bias. We propose these aspects of the co-constitution of chaos are considered in the creation of person-centered policy, and non-discriminatory, safe criminal justice spaces.
Lateral Extra-Articular Tenodesis as an Adjunct to ACL Reconstruction
Authors: McGovern Madeline M. , Yalcin Sercan , Lowenstein Natalie A. , Mazzocca Jillian L. , Matzkin Elizabeth G. , Medina Giovanna
Published: January 2025

Background:

Lateral extra-articular tenodesis (LET) is a surgical technique used to decrease the risk of anterior cruciate ligament reconstruction (ACLR) failure by supplementing internal rotational stability and reducing pivot shift.

Indications:

A growing body of literature indicates that LET should be performed for patients under 25 years, those with increased posterior tibial slope and ligamentous laxity, and elite athletes in cutting and/or pivoting sports. Additional indications include patients with grade 2 pivot shift or greater and those with a history of anterior cruciate ligament graft failure.

Technique Description:

Surgeon preference determines LET and ACLR sequence. Anatomic landmarks are identified and marked. A 5-cm incision is made in line with the iliotibial (IT) band from Gerdy's tubercle toward the lateral epicondyle. Dissection is carried to the IT band. Approximately 1 cm from the posterior border of the IT band, a full-thickness graft of 7 to 8 cm in length and 1 cm in width is harvested proximally and then whipstitched. A varus stress applies ligamentous tension and aids in lateral collateral ligament (LCL) identification. The LCL is dissected out, and the graft is passed underneath it. An all-suture anchor placed approximately 1 to 2 cm proximal and posterior to the lateral epicondyle and the knee is positioned in neutral rotation and at approximately 60° of flexion. The graft is passed inside the suture loop with an additional knot tied over the top using the needled suture. The IT band is then repaired side to side. Remaining subcutaneous tissue and skin are closed in standard fashion based on the order of the surgery.

Results:

In the STABILITY randomized controlled trial, 2-year outcomes demonstrated a clinically and statistically significant decrease in clinical failure from 40% to 25% and graft rupture rate from 11% to 4% with the addition of LET to ACLR with hamstring autograft. Similar return-to-sport rate was seen between cohorts. A meta-analysis of 6 studies examining ACLR versus ACLR + LET in individuals undergoing primary ACLR reported a reduced incidence of graft failure and postoperative anterolateral rotatory instability.

Discussion/Conclusion:

LET is a technique that can help reduce the risk of ACLR failure. Our technique employs a knotless suture anchor to confer anterolateral rotatory stability in the setting of ACLR.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Multidimensional perfectionism and daily self-control episodes
Authors: Altstötter-Gleich Christine , Prestele Elisabeth , Grommisch Gloria , Lischetzke Tanja
Published: January 2025

The study examined the interrelations of perfectionistic concerns and perfectionistic strivings on self-control. Going beyond previous research, we examined dispositional and daily components of self-control. In addition, we tested opposing predictions of the tripartite model (postulating that high perfectionist strivings combined with high perfectionist concerns are associated with negative outcomes) and the 2 × 2 model (postulating that this is true for low perfectionistic strivings combined with high perfectionistic concerns). Over the course of 9 months, 183 teacher trainees participated in approximately 5 ambulatory assessment periods (each lasting 10 days), that preceded a challenging performance situation. Negative associations between perfectionistic concerns and dispositional self-control were confirmed. In addition, the results showed that high perfectionistic concerns also interfered with three of the five daily self-control components. Contrasting statistical effects of perfectionistic strivings supported the assumptions of the 2 × 2 model and suggest that perfectionistic strivings buffer the detrimental effects of perfectionistic concerns.
Content, uptake and adherence of exercise interventions after an acute exacerbation of COPD: a scoping review
Authors: Wuyts Marieke , Demeyer Heleen , Vandendriessche Thomas , Cui Yiting , Mellaerts Paulien , Janssens Wim , Troosters Thierry
Published: January 2025

Introduction

Pulmonary rehabilitation is underutilised in patients after an acute exacerbation of COPD (AECOPD). Retrieving information regarding the setting, training modalities and the uptake and adherence to exercise interventions for these individuals in a vulnerable state could potentially guide future research.

Aim

To provide a comprehensive review of the existing literature on the content, uptake and adherence of different exercise interventions for patients after an AECOPD.

Methods

Eight different databases were searched for 1) patients experiencing an AECOPD and 2) performing any form of exercise intervention. Information on content, uptake and adherence was collected and the Consensus on Exercise Reporting Template (CERT) checklist was performed for each included record.

Results

59 distinct interventions were identified between 1998 and 2023 including a total of 9238 patients. All studies included patients requiring hospitalisation for the AECOPD, four studies additionally included patients not requiring hospitalisation for the AECOPD. Nine different settings were identified, with the majority of studies conducted in an inpatient setting (n=26) and including whole-body and strength exercises. The overall uptake was mentioned in 38 (62%) studies and was 70% with a 13% dropout rate. No paper reported the full CERT checklist. Adherence was defineda prioriin 16 (27%) studies, with the most common definition being attendance of >80% of sessions.

Conclusion

Studies properly reporting on the uptake and adherence of well-described interventions, including information regarding fidelity, are needed to further investigate suitable programmes for patients experiencing an AECOPD.
Airway clearance techniques for people with acute exacerbation of COPD: a scoping review
Authors: Poncin William , Schrøder Christine , Oliveira Ana , Herrero Beatriz , Cnockaert Pierre , Gely Lucile , Osadnik Christian , Reychler Gregory , Mechlenburg Inger , Spinou Arietta
Published: January 2025

Introduction

Acute exacerbations of COPD (AECOPD) often involve mucus hypersecretion. Thus, management of sputum retention is critical. However, the use of airway clearance techniques (ACTs) in people with AECOPD across different healthcare settings and factors influencing their selection remain unclear.

Objective

To identify and map ACTs used for AECOPD in different healthcare settings and the factors influencing clinical decision-making worldwide.

Methods

Four electronic databases and grey literature were searched from 1995 to December 2023, with hand-searching of eligible records. The Joanna Briggs Institute methodology for scoping reviews was followed.

Results

25 articles were included: 14 clinical studies, five guidelines/statements and six surveys/audits. Clinical studies reported the use of a wide range of single or combined ACTs, with no clear pattern in using particular ACTs in different parts of the world. Recent guidelines advise using ACTs for certain patients with AECOPD, particularly those with hypersecretion, with most guidelines recommending positive expiratory pressure (PEP) therapy. According to surveys, the most used ACTs in Australia and Europe are active cycle of breathing techniques, PEP or forced expiratory technique, while vibrations are most frequently used in Canada. Factors influencing the selection of specific ACTs include the presence of contraindications, level of dyspnoea, access to resources/equipment and ease of learning/performing the technique. All information was derived from hospital settings.

Conclusions

This scoping review identified and mapped ACTs used for people with AECOPD worldwide and their decision-making factors. Future work should focus on community settings.
Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair
Authors: Kim Min-ah , Kim Banseok , Jeon Jihyeon , Lee Jonghyun , Jang Hyeji , Baek Minjae , Seo Sang-Uk , Shin Dongkwan , Dutta Anindya , Lee Kyung Yong
Published: January 2025

Background

Double-strand breaks (DSBs) are primarily repaired through non-homologous end joining (NHEJ) and homologous recombination (HR). Given that DSBs are highly cytotoxic, PARP inhibitors (PARPi), a prominent class of anticancer drugs, are designed to target tumors with HR deficiency (HRD), such as those harboring BRCA mutations. However, many tumor cells acquire resistance to PARPi, often by restoring HR in HRD cells through the inactivation of NHEJ. Therefore, identifying novel regulators of NHEJ could provide valuable insights into the mechanisms underlying PARPi resistance.

Methods

Cellular DSBs were assessed using neutral comet assays and phospho-H2AX immunoblotting. Fluorescence-based reporter assays quantified repair via NHEJ or HR. The recruitment of proteins that promote NHEJ and HR to DSBs was analyzed using immunostaining, live-cell imaging following laser-induced microirradiation, and FokI-inducible single DSB generation. Loss-of-function experiments were performed in multiple human cancer cell lines using siRNA-mediated knockdown or CRISPR-Cas9 gene knockout. Cell viability assays were conducted to evaluate resistance to PARP inhibitors. Additionally, bioinformatic analyses of public databases were performed to investigate the association between TLK expression and BRCA1 status.

Results

We demonstrate that human tousled-like kinase (TLK) orthologs are essential for NHEJ-mediated repair of DSBs and for PARPi sensitivity in cells with BRCA1 mutation. TLK1 and TLK2 exhibit redundant roles in promoting NHEJ, and their deficiency results in a significant accumulation of DSBs. TLKs are required for the proper localization of 53BP1, a key factor in promoting the NHEJ pathway. Consequently, TLK deficiency induces PARPi resistance in triple-negative breast cancer (TNBC) and ovarian cancer (OVCA) cell lines with BRCA1 deficiency, as TLK deficiency in BRCA1-depleted cells, impairs 53BP1 recruitment to DSBs and reduces NHEJ efficiency, while restoring HR.

Conclusions

We have identified TLK proteins as novel regulators of NHEJ repair and PARPi sensitivity in BRCA1-depleted cells, suggesting that TLK repression may represent a previously unrecognized mechanism by which BRCA1 mutant cancers acquire PARPi resistance.
Integrating functional proteomics and next generation sequencing reveals potential therapeutic targets for Taiwanese breast cancer
Authors: Ku Wei-Chi , Liu Chih-Yi , Huang Chi-Jung , Liao Chen-Chung , Huang Yen-Chun , Kong Po-Hsin , Chen-Chan Hsieh , Tseng Ling-Ming , Huang Chi-Cheng
Published: January 2025

Integrating functional proteomics and next-generation sequencing (NGS) offers a comprehensive approach to unraveling the molecular intricacies of breast cancer. This study investigates the functional interplay between genomic alterations and protein expression in Taiwanese breast cancer patients. By analyzing 61 breast cancer samples using tandem mass tag (TMT) labeling and mass spectrometry, coupled with whole-exome sequencing (WES) or targeted sequencing, we identified key genetic mutations and their impact on protein expression. Notably, pathogenic variants in BRCA1, BRCA2, PTEN, and PIK3CA were found to be clinically relevant, potentially guiding targeted therapy decisions. Additionally, we discovered trans correlations between specific gene alterations (FANCA, HRAS, PIK3CA, MAP2K1, JAK2) and the expression of 22 proteins, suggesting potential molecular mechanisms underlying breast cancer development and progression. These findings highlight the power of integrating proteomics and NGS to identify potential therapeutic targets and enhance personalized medicine strategies for Taiwanese breast cancer patients.
Physalis peruviana calyces extract ameliorate oxidative stress, inflammation, and immune loss in rats-exposed to hexaflumuron
Authors: Hashem Mona M. , Hassanen Eman I. , Hassan Neven H. , Ibrahim Marwa A. , Issa Marwa Y. , Farag Mohamed A. , Hamdy Sherif A.
Published: January 2025

Background

Hexaflumuron (HFM), a common pesticide, can disrupt the immune system and cause oxidative stress. This study investigated the potential of Physalis peruviana L. calyces extract (PP) to counteract these effects in rats.

Methods

Rats were divided into 6 groups including control, PP-treated, HFM-exposed, and co-treated (HFM + PP) groups. Immune function, antioxidant activity, and organ damage were assessed. Furthermore, UPLC-MS/MS analysis identified potential bioactive compounds in PP extract.

Results

HFM exposure suppressed immune responses and caused organ damage. Notably, the co-administration of PP extract with HFM reversed these effects, indicating its ability to reduce oxidative stress and protect the immune system. UPLC-MS/MS analysis of PP calyces ethanolic extract revealed its richness in various health-promoting metabolites, including acyl sucrose sugar, withanolides, and flavonoids, which may provide valuable insight into the underlying mechanisms of PP’s calyces protective effects against HFM toxicity.

Conclusions

This study provides novel insights into the potential of P. peruviana L. calyces ethanolic extract as a natural agent to counteract the harmful effects of HFM exposure. These findings have significant implications for developing effective strategies to mitigate pesticide-induced toxicity and promote human health.
Nursing staff and supervisors perceptions on stress and resilience: a qualitative study
Authors: Helaß Madeleine , Greinacher Anja , Genrich Melanie , Müller Andreas , Angerer Peter , Gündel Harald , Junne Florian , Nikendei Christoph , Maatouk Imad
Published: January 2025

Background

Supervisor–subordinate relationship is high relevant in dealing with work-related stress and providing a compassionate, high-quality, and safe nursing care while meeting the needs of the hospital. Our aim was to assess the predisposing risk and resilience factors of the stress of nursing staff as well as to explore the common and distinctive perceptions of these factors between nurses without a managerial position (nursing staff) and employees in a supervising position (nurse managers, ward nurses).

Design

Generic qualitative study using half-standardized interviews.

Methods

Fifty nurses and supervisors from different departments from a German hospital of maximum medical care participated in this study between August and November 2018. Nineteen face-to-face interviews and five focus groups were conducted. Transcripts were subjected to structured qualitative content analysis.

Results

Systematised in Lazarus’s transactional model, nurses, and supervisors mentioned similar risk and resilience factors of stress. Disagreement in suggested responsibility for nurses’ stress or health and an evaluation of implemented measures meeting the nurses’ needs are discussed.

Conclusion

Nursing staff and supervisors should enforce exchange to reduce disagreements in perceptions and to improve mutual understanding. Furthermore, measures to meet nurses’ needs to minimize stress and to improve collaboration and job satisfaction should be developed in close coordination with the target group. The focus should be placed on restructuring training and education programs with supplementation of self-responsibility promotion.

Trail registration

The study was registered with the German Register for Clinical Studies (DRKS 00013482) on 09 March 2018.
Neutrophil extracellular traps (NETs) are increased in rheumatoid arthritis-associated interstitial lung disease
Authors: Xue Jing , Nian Miaomiao , Liang Yangyang , Zhu Zeqin , Hu Zhenyu , Jia Yuanyuan , Chi Shuhong , Chen Juan
Published: January 2025

Background

Neutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms.

Methods

Single-cell sequencing was used to identify changes in the quantity and function of neutrophils in the lung tissue of a zymosan A (ZYM)-induced interstitial pneumonia arthritis model. Additionally, nuclear receptor 4A3 (NR4A3) interference was performed in HL-60 cells to assess its impact on NET formation and the transformation of MRC-5 cells into myofibroblasts. The clinical relevance of plasma myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (Cit-H3), and cell-free DNA was evaluated in RA-ILD patients with different imaging types via a commercial enzyme-linked immunosorbent assay (ELISA).

Results

In the ZYM-treated SKG mouse model, which recapitulates key features of RA-ILD, an increased population of neutrophils in the lung tissue was primarily responsible for NET formation. Mechanistically, we found that interference with NR4A3 expression enhanced NET formation in HL-60 cells, which in turn promoted the differentiation of MRC-5 cells into myofibroblasts. Clinically, plasma MPO-DNA levels are elevated in patients with RA-nonspecific interstitial pneumonia (RA-NSIP), whereas Cit-H3 levels are elevated in RA-usual interstitial pneumonia (RA-UIP) patients compared with healthy subjects. ROC curve analysis further revealed that the combination of plasma MPO-DNA, rheumatoid factor (RF), and anti-citrullinated protein (anti-CCP) and the combination of Cit-H3, RF, and anti-CCP were superior diagnostic panels for NSIP and UIP in RA-ILD patients, respectively. Moreover, compared with those from healthy controls, neutrophils from patients with RA-UIP and RA-NSIP demonstrated a significantly increased ability to form NETs and induce the differentiation of MRC-5 cells into myofibroblasts. Specifically, RA-UIP patients exhibited a greater capacity for NET formation and the differentiation of MRC-5 cells into myofibroblasts than did RA-NSIP patients.

Conclusions

These findings suggest that targeting NETs may be a novel therapeutic approach for treating ILD in RA patients.
Estimating mortality attributable to alcohol or tobacco – a cohort study from Germany
Authors: John Ulrich , Rumpf Hans-Jürgen , Hanke Monika , Meyer Christian
Published: January 2025

Background

Little is known about mortality from four disorder combinations: fully attributable to alcohol or tobacco, partly attributable to both alcohol and tobacco, to tobacco only, to alcohol only.

Aim

To analyze whether residents who had disclosed risky alcohol drinking or daily tobacco smoking had a shorter time to death than non-risky drinkers and never daily smokers twenty years later according to the disorder combinations.

Methods

A random adult general population sample (4,075 study participants) of a northern German area had been interviewed in the years 1996–1997. Vital status and death certificate data were gathered 2017–2018. The data analysis included estimates of alcohol- or tobacco-attributable mortality using all conditions given in the death certificate and alternatively the underlying cause of death only.

Results

Among 573 deaths, 71.9–94.1% had any alcohol- or tobacco-attributable disorder depending on the estimate. Risky alcohol consumption and daily tobacco smoking at baseline were related to disorders in the death certificate according to the combinations. Deaths with an alcohol- and tobacco-attributable disorder were related to risky alcohol consumption (subhazard ratio 1.57; 95% confidence interval 1.25–1.98) and to daily tobacco smoking at baseline (subhazard ratio 1.85; 95% confidence interval 1.42–2.41).

Conclusion

First, more than 70% of the deceased persons had one or more alcohol- or tobacco-attributable disorders. This finding suggests that total mortality seems to be the suitable outcome if potential effects of alcohol or tobacco consumption in a general population are to be estimated. Second, the relations of risky alcohol consumption and tobacco smoking with time to death speak in favor of the validity of alcohol- and of tobacco-attributable disorders in death certificates and of considering both alcohol consumption and tobacco smoking if attributable deaths are to be estimated.
Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023
Authors: Kaufman Christina , D’Andrea Anaïs , Hackenberg Annette , Poms Martin , Braissant Olivier , Häberle Johannes
Published: January 2025

Background

Cerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine.

Results

The patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first.

Conclusions

The data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.
Ferroelectric capacitive memories: devices, arrays, and applications
Authors: Zhou Zuopu , Jiao Leming , Zheng Zijie , Chen Yue , Han Kaizhen , Kang Yuye , Zhang Dong , Wang Xiaolin , Kong Qiwen , Sun Chen , Xie Jiawei , Gong Xiao
Published: January 2025

Ferroelectric capacitive memories (FCMs) utilize ferroelectric polarization to modulate device capacitance for data storage, providing a new technological pathway to achieve two-terminal non-destructive-read ferroelectric memory. In contrast to the conventional resistive memories, the unique capacitive operation mechanism of FCMs transfers the memory reading and in-memory computing to charge domain, offering ultra-high energy efficiency, better compatibility to large-scale array, and negligible read disturbance. In recent years, extensive research has been conducted on FCMs. Various device designs were proposed and experimentally demonstrated with progressively enhanced performance, showing remarkable potential of the novel technology. This article summarizes several typical FCM devices by introducing their mechanisms, comparing their performance, and discussing their limitations. We further investigate the capacitive crossbar array operation and review the recent progress in the FCM integration and array-level demonstrations. In addition, we present the computing-in-memory applications of the FCMs to realize ultra-low-power machine learning acceleration for future computing systems.
Diurnal and daily fluctuations in levels of the urinary oxidative stress marker 8-hydroxyguanosine in spot urine samples
Authors: Li Yun-Shan , Fujisawa Koichi , Kawai Kazuaki
Published: January 2025

Background

Urinary 8-hydroxyguanosine (8-OHGuo) levels serve as a biomarker for oxidative stress and hydroxyl radical–induced RNA damage. Evaluating the diurnal and daily fluctuations in urinary 8-OHGuo excretion levels is essential for understanding its implications. However, research in this area remains limited. In this study, we aim to investigate the diurnal and daily fluctuations in 8-OHGuo levels as well as the factors that influence these variations, using spot urine samples.

Methods

Urine samples were collected from seven healthy participants during each urination from the time of awakening until 24:00 h to evaluate diurnal variations. To assess daily fluctuations, urine samples were collected from 18 healthy participants at the time of awakening for 23 consecutive days. The urinary 8-OHGuo levels were measured using an HPLC-ECD method.

Results

No significant variations were observed in the diurnal levels of urinary 8-OHGuo among non-smokers. Conversely, the daily variation of 8-OHGuo in the urine of the smoker was significant, with a coefficient of variation of 18.71%. Each individual maintained a characteristic value despite some diurnal fluctuations. Furthermore, the daily levels of 8-OHGuo exhibited a range of variations influenced by lifestyle factors, including mental state, sleep duration, smoking, menstrual cycle, and dietary habits.

Conclusion

As a specific marker of RNA oxidation, 8-OHGuo provides unique insights distinct from those provided by the widely used DNA oxidation marker 8-hydroxydeoxyguanosine as an indicator of oxidative stress. Urinary 8-OHGuo could serve as a valuable biomarker for managing and preventing oxidative stress–related diseases, provided that the specific range of daily variations is established. The high daily variation in urinary 8-OHGuo levels necessitates the use of multiple samples to accurately determine individual levels. However, further research with large sample sizes will help to validate these findings.