bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis
Authors: Al Wattar Bassel H. , Rimmer Michael P. , Teh Jack J. , Mackenzie Scott C. , Ammar Omar F. , Croucher Carolyn , Anastasiadis Eleni , Gordon Patrick , Pacey Allan , McEleny Kevin , Sangster Phillipa 
Published: July 2024

Abstract
Background
Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy.

Objective
We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.

Methods
We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).

Results
We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78–3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23–4.62), tamoxifen (SMD − 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD − 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44–2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.

Conclusion
There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.

PROSPERO
CRD42023430179.
Nurses’ opinions on euthanasia in Spain: an evaluation using a new version of the EAS
Authors: Lerma-García Daniel , Parra-Fernández María Laura , Romero-Blanco Cristina , Olmo-Mora María Soledad , Onieva-Zafra María Dolores 
Published: July 2024

Abstract
Background
Bioethical dilemmas at the end of life have led to regularization processes for the provision of medical assistance in dying patients in different countries. Since the regulation of euthanasia in Spain in 2021, the euthanasia act has been included as one of the benefits of the health system, which has undergone uneven development and implementation in different autonomous communities. The aim of this study was to review the Spanish version of the Euthanasia Attitude Scale following the partial modification of four items.

Methods
A cross-sectional study was conducted with a non-probabilistic sample of Spanish health workers from Islas Baleares. A self-reported sociodemographic questionnaire and the Euthanasia Attitude Scale were used for data collection. The psychometric properties of the scale were assessed, including reliability and validity, using a confirmatory factor analysis and a parallel analysis.

Results
The Cronbach's alpha of the EAS was α = 0.892, which implies good internal consistency. According to the confirmatory factor analysis, a Kaiser–Meyer–Olkin–value of 0.938 was obtained, and the result of Bartlett's test of sphericity was < 0.001. The questionnaire included four loading factors, which explained up to 56.99% of the variance. The parallel analysis revealed three significant factors and a fourth, less interpretative factor.

Conclusions
The EAS-ES-R is a valid instrument for assessing the attitudes toward euthanasia of both trainees and practicing health professionals. It may also be of vital importance in detecting training, support and implementation needs for laws regulating euthanasia in Spain.
Learning from a crisis: a qualitative study on how nurses reshaped their work environment during the COVID-19 pandemic
Authors: de Vos Annemarie J. B. M. , de Kok Eline , Maassen Susanne M. , Booy Monique , Weggelaar-Jansen Anne Marie J. W. M. 
Published: July 2024

Abstract
Background
The global nursing shortages exacerbated by the COVID-19 pandemic necessitated a drastic reorganization in nursing practices. Work routines, the composition of teams and subsequently mundane nursing practices were all altered to sustain the accessibility and quality of care. These dramatic changes demanded a reshaping of the nurses’ work environment. The aim of this study was to explore how nurses reshaped their work environment in the early stages of the COVID-19 pandemic.

Methods
A descriptive study comprising 26 semi-structured interviews conducted in a large Dutch teaching hospital between June and September 2020. Participants were nurses (including intensive care unit nurses), outpatient clinic assistants, nurse managers, and management (including one member of the Nurse Practice Council). The interviews were analysed with open, axial, and selective coding.

Results
We identified five themes: 1) the Nursing Staff Deployment Plan created new micro-teams with complementary roles to meet the care needs of COVID-19 infected patients; 2) nurse-led adaptations effectively managed the increased workload, thereby ensuring the quality of care; 3) continuous professional development ensured adequate competence levels for all roles; 4) interprofessional collaboration resulted in experienced solidarity, a positive atmosphere, and increased autonomy for nurses; and, 5) supportive managers reduced nurses’ stress and improved work conditions.

Conclusions
This study showed that nurses positively reshaped their work environment during the COVID-19 pandemic. They contributed to innovative solutions in an environment of equal interprofessional collaboration, which led to greater respect for their knowledge and competencies, enhanced their autonomy and improved management support.
Factors associated with health CEO turnover - a scoping review
Authors: Mathew Nebu Varughese , Liu Chaojie , Khalil Hanan 
Published: July 2024

Abstract
Background
Chief Executive Officer’s (CEO) are integral leaders of health care organisation. Over the last two decades in United States (US) hospitals, it has been noted that CEO turnover rates are increasing, and it was reported that the CEO turnover rates have augmented from 14% in 2008 to 18% in 2017 in the private sector. In Australia, it was discovered that during two years, 41 executives had 18 distinct positions. It has been highlighted that the increasing CEO turnover is a major issue for Australian and international health care organisations. Some of the negative consequences of CEO turnover include organisational instability, high financial costs, loss of human capital and adverse effects on staff morale and patient care.

Objective
Our scoping review aimed to map and summarise the evidence associated with CEO turnovers in both health and non-health setting, and answer the following questions: 1. What are the reasons for CEO departure?, 2. What are the strategies to minimise CEO turnover?

Results
A protocol explaining the objectives, inclusion criteria and methods for this scoping review were specified in advance and published. This scoping review included 17 studies (13 health and 4 non-health setting) published over a 31-year period that investigated and described the increasing CEO turnover rates. All 17 studies identified causes of CEO turnover along with certain studies identifying facilitators of CEO retention. We classified CEO’s departure reasons into three major themes: organizational, performance, and personal. Organisational factors include CEO departures due to issues within the organisation, performance factors include issues with CEO’s work and personal factors captures personal reasons for CEO’s leaving their job.

Conclusion
CEOs are under immense pressure to deliver good results and drive growth while satisfying the interests of internal and external stakeholders. There are various reasons for CEO’s departure however the most common factor identified is organisational.
Efficacy and safety of maintenance therapy with anlotinib for advanced cholangiocarcinoma after first-line chemotherapy and the variations in efficacy based on different neutrophil-to-lymphocyte ratio (NLR)
Authors: Li Hui , Zhang Jue , Gu Lili 
Published: July 2024

Abstract
Objective
This study aimed to evaluate the clinical efficacy and safety of anlotinib as maintenance therapy in patients with advanced cholangiocarcinoma following first-line chemotherapy.

Methods
This retrospective study enrolled 154 patients with advanced biliary tract cancer admitted to the hospital between January 2020 and December 2022. All patients received first-line intravenous chemotherapy with gemcitabine combined with cisplatin, oxaliplatin, or tegafur. Among the 106 patients who achieved disease control, 47 received oral anlotinib hydrochloride (12 mg daily, 2 weeks on/1 week off) as maintenance therapy. Clinical efficacy, including ORR, DCR, DOR, PFS, and OS, was compared between the anlotinib maintenance and non-maintenance groups. Subgroup analysis based on NLR levels was also performed.

Results
Among the 47 anlotinib maintenance patients, the ORR was 21.28% and the DCR was 51.06%. The median DOR was 36 weeks, and the median PFS was 43 weeks in the anlotinib group, versus 28 weeks and 38 weeks in the non-maintenance group, respectively. The median OS was not reached in the anlotinib group but was 48 weeks in the non-maintenance group. Patients receiving anlotinib maintenance had significantly longer DOR, PFS, and OS (all p < 0.05). Patients with low NLR levels had better survival benefits from anlotinib.

Conclusion
Maintenance therapy with anlotinib demonstrates potential efficacy and a reliable safety profile in patients with advanced cholangiocarcinoma following first-line treatment. The efficacy of anlotinib therapy appears to be influenced by NLR levels. Further validation with larger sample sizes is warranted to strengthen the robustness and reliability of the results.
Novel energy optimizer, meldonium, rapidly restores acute hypobaric hypoxia-induced brain injury by targeting phosphoglycerate kinase 1
Authors: Liu Fengying , He Huanhuan , Yang Weijie , Wang Daohui , Sui Xin , Sun Yangyang , Wang Shuai , Yang Yi , Xiao Zhenyu , Yang Jun , Wang Yongan , Luo Yuan 
Published: July 2024

Abstract
Background
Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury.

Methods
We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression.

Results
The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones.

Conclusion
These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.
The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017–2023
Authors: Li Rukai , Meng Weiwei , Zuo Yunhai , Xu Yanli , Wu Shaonan 
Published: July 2024

AbstractCervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People’s Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers.
Successful and sustained implementation of a behaviour-change informed strategy for emergency nurses: a multicentre implementation evaluation
Authors: Curtis Kate , Kennedy Belinda , Considine Julie , Murphy Margaret , Lam Mary K. , Aggar Christina , Fry Margaret , Shaban Ramon Z. , Kourouche Sarah 
Published: July 2024

Abstract
Background
Implementing evidence that changes practice in emergency departments (EDs) is notoriously difficult due to well-established barriers including high levels of uncertainty arising from undifferentiated nature of ED patients, resource shortages, workload unpredictability, high staff turnover, and a constantly changing environment. We developed and implemented a behaviour-change informed strategy to mitigate these barriers for a clinical trial to implement the evidence-based emergency nursing framework HIRAID® (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication, and reassessment) to reduce clinical variation, and increase safety and quality of emergency nursing care.

Aim
To evaluate the behaviour-change-informed HIRAID® implementation strategy on reach, effectiveness, adoption, quality (dose, fidelity) and maintenance (sustainability).

Methods
An effectiveness-implementation hybrid design including a step–wedge cluster randomised control trial (SW-cRCT) was used to implement HIRAID® with 1300 + emergency nurses across 29 Australian rural, regional, and metropolitan EDs. Evaluation of our behaviour-change informed strategy was informed by the RE-AIM Scoring Instrument and measured using data from (i) a post HIRAID® implementation emergency nurse survey, (ii) HIRAID® Instructor surveys, and (iii) twelve-week and 6-month documentation audits. Quantitative data were analysed using descriptive statistics to determine the level of each component of RE-AIM achieved. Qualitative data were analysed using content analysis and used to understand the ‘how’ and ‘why’ of quantitative results.

Results
HIRAID® was implemented in all 29 EDs, with 145 nurses undertaking instructor training and 1123 (82%) completing all four components of provider training at 12 weeks post-implementation. Modifications to the behaviour-change informed strategy were minimal. The strategy was largely used as intended with 100% dose and very high fidelity. We achieved extremely high individual sustainability (95% use of HIRAID® documentation templates) at 6 months and 100% setting sustainability at 3 years.

Conclusion
The behaviour-change informed strategy for the emergency nursing framework HIRAID® in rural, regional, and metropolitan Australia was highly successful with extremely high reach and adoption, dose, fidelity, individual and setting sustainability across substantially variable clinical contexts.

Trial registration
ANZCTR, ACTRN12621001456842. Registered 25 October 2021.
Clinical efficacy of arthroscopic high-intensity suture binding combined with button plate suspension fixation in the treatment of posterior cruciate ligament tibial avulsion fractures
Authors: Zhang Pei , Liu Wenkang , Chen Pengtao , Fei Wenyong , Hu Hansheng , Wen Dan 
Published: July 2024

Abstract
Purpose
To assess the clinical efficacy of arthroscopic treatment for posterior cruciate ligament (PCL) tibial avulsion fractures using high-intensity suture binding combined with button plate suspension fixation.

Methods
We retrospectively analyzed clinical data from 32 patients with PCL tibial avulsion fractures treated at our hospital from July 2020 to August 2023. We recorded operation time, intraoperative and postoperative complications, and used imaging to assess fracture reduction and healing. Pain and knee function were evaluated using the Visual Analogue Scale (VAS), range of knee motion, Lysholm score, and International Knee Documentation Committee (IKDC) score.

Study Design
Case series; Level of evidence, 4.

Results
All patients were followed for 6 to 18 months, averaging 13.6 months. All incisions healed successfully without postoperative complications. X-rays taken on the first postoperative day showed satisfactory fracture reduction. Three-month post-surgery imaging confirmed healed fractures and no internal fixation failures. At the final follow-up, knee function was well recovered, with only one patient exhibiting a positive posterior drawer test of degree I. Furthermore, the mean VAS score was 0. 5 (range 0.0 to 1.0), active knee extension was 2. 2° (range 0.0 to 5.0), and active knee flexion was 137.7° (range 130.0 to 145.0). The mean Lysholm score was 91.5(range 89.3 to 94.0), and the IKDC score averaged 83.8 ± 3.7, and these outcomes showed statistically significant improvement from preoperative levels (P < 0.001).

Conclusions
Arthroscopic high-intensity suture binding combined with button plate suspension fixation for PCL tibial avulsion fractures offers several benefits: it is minimally invasive, results in less postoperative pain, enables earlier functional exercise, and provides satisfactory clinical outcomes with fewer complications.
Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating the brain
Authors: Gaire Sushil , An Jiawei , Yang Haijie , Lee Keon Ah , Dumre Manisha , Lee Eun Jeong , Park Sang-Myun , Joe Eun-Hye 
Published: July 2024

AbstractIn this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.
IGF1R signaling induces epithelial-mesenchymal plasticity via ITGAV in cutaneous carcinoma
Authors: Lopez-Cerda Marta , Lorenzo-Sanz Laura , da Silva-Diz Victoria , Llop Sandra , Penin Rosa M. , Bermejo Josep Oriol , de Goeij-de Haas Richard , Piersma Sander R. , Pham Thang V. , Jimenez Connie R. , Martin-Liberal Juan , Muñoz Purificación 
Published: July 2024

Abstract
Background
Early cutaneous squamous cell carcinomas (cSCCs) generally show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits associated with tumor relapse, metastasis, and poor survival. Currently, the mechanisms involved in cSCC progression are unclear, and the established markers are suboptimal for accurately predicting the clinical course of the disease.

Methods
Using a mouse model of cSCC progression, expression microarray analysis, immunofluorescence and flow cytometry assays, we have identified a prognostic biomarker of tumor relapse, which has been evaluated in a cohort of cSCC patient samples. Phosphoproteomic analysis have revealed signaling pathways induced in epithelial plastic cancer cells that promote epithelial-mesenchymal plasticity (EMP) and tumor progression. These pathways have been validated by genetic and pharmacological inhibition assays.

Results
We show that the emergence of epithelial cancer cells expressing integrin αV (ITGAV) promotes cSCC progression to a mesenchymal state. Consistently, ITGAV expression allows the identification of patients at risk of cSCC relapse above the currently employed clinical histopathological parameters. We also demonstrate that activation of insulin-like growth factor-1 receptor (IGF1R) pathway in epithelial cancer cells is necessary to induce EMP and mesenchymal state acquisition in response to tumor microenvironment-derived factors, while promoting ITGAV expression. Likewise, ITGAV knockdown in epithelial plastic cancer cells also blocks EMP acquisition, generating epithelial tumors.

Conclusions
Our results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs.

Graphical Abstract
During cSCC progression, cancer cells evolve from the epithelial to the mesenchymal state, which is associated with poor prognosis. The current investigation reveals that, at intermediate cSCC stages (MD/PD-SCC), epithelial cancer cells activate IGF1R and ITGAV signaling to acquire EMP and progress to the aggressive mesenchymal state in response to TME-derived factors. In addition, ITGAV allows the identification of these epithelial plastic cancer cells and functions as a prognostic biomarker of tumor relapse.