bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Long Way to Go: A Scenario for Clinical Trials of PI3K Inhibitors in Treating Cancer
Authors: Trigueiros Bárbara Adriana Ferreira dos Santos , Santos Ivan José Santana , Pimenta Fabricia Pires , Ávila Andréa Rodrigues 
Published: March 2024

Background Alterations in PI3K function are directly related to cancer, making PI3K inhibitors suitable options for anticancer therapies. Information on therapy using different types of PI3K inhibitors is available in literature, providing indications of trends in developing new therapies. Although some studies on PI3K inhibitors for cancer treatment provide clinical evidence, they do not allow a careful search for potential PI3K inhibitors conducted by development indicators. Here, we performed a foresight study of clinical trials involving PI3K inhibitors from the past 11 years using indicators of clinical evolution to identify technological trends and provide data for supporting recommendations for new study designs. Methods A comprehensive foresight study was designed based on documents from clinical trials on PI3K inhibitors to perform a systematic and comparative analysis, in order to identify technological trends on new cancer therapies. Results Our results demonstrate that total number of clinical trials has decreased over the years and, currently, there is a clear prevalence of studies using isoform-specific inhibitors in combined interventions. Clinical trials in Phases I and II were the most frequently found in the database, whereas Phase III trials correspond to 7% of studies. The measurement of clinical trials progression using indicators (drugs in Phase III profile, top-10 drugs, and top-10 combined drugs) demonstrated that the 3 new medicines BKM120, IBI-376, and PF-05212384 have a high potential to provide more efficient cancer treatment in combined interventions. These data also include the groups of targets for each drug, providing a useful and reliable source for design new combinations to overcome the resistance and the poor tolerability observed in some PI3K therapies. Conclusions The establishment of development indicators based on clinical trials for cancer treatment was useful to highlight the clinical investment in 3 new PI3K drugs and the advantages of combine therapy using FDA-approved drugs.
Neoadjuvant PD-1 Plus Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Qian Ting , Liu Delin , Cao Guochun , Chen Zhipeng , Zhang Qin 
Published: March 2024

Background Clinical studies have shown that programmed cell death-1 (PD-1) inhibitors can activate T cells and inhibit cancer growth. Therefore, the use of a PD-1 inhibitor plus chemotherapy as neoadjuvant chemotherapy for locally advanced esophageal cancer is worth further exploration. Methods Patients with locally advanced esophageal squamous cell carcinoma were enrolled in this study to receive two cycles of a preoperative combination of toripalimab, paclitaxel, and cisplatin. Efficacy was evaluated after two treatment cycles. The patients’ postoperative pathological staging was analyzed and compared. Surgery was performed within 42 days of the start date of the last chemotherapy cycle. Results Neoadjuvant immunochemotherapy achieved a high pathologic complete response (pCR) rate (29.0%), major pathological response rate (41.9%), and objective response rate (80.6%) and demonstrated statistically significant downstaging after neoadjuvant therapy ( P < .05) with manageable treatment-related adverse effects. No significant association was found between PD-L1 level and pCR ( P = .365). In addition, R0 resection was achieved in all 31 (100%) patients during surgery. For all the included patients, the one-year progression-free survival rate was 87.1% (95% CI: 75.3%-98.9%), the one-year overall survival (OS) rate was 96.8% (95% CI: 79.8%-95.9%), and the two-year OS rate was 83.9% (95% CI: 71.6%-92.2%). Conclusions Our findings indicate that this combination may be a potential neoadjuvant therapy regimen in this setting.
Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke
Authors: Mead Gillian , Graham Catriona , Lundström Erik , Hankey Graeme J , Hackett Maree L , Billot Laurent , Näsman Per , Forbes John , Dennis Martin 
Published: March 2024

Background: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. Methods: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. Findings: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2–15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. Interpretation: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.
Supporting work participation for adults with hand and upper limb conditions: A survey of the British Association of hand therapists
Authors: Newington Lisa , Ceh Daniel , Sandford Fiona , Parsons Vaughan , Madan Ira 
Published: March 2024

Introduction Musculoskeletal disorders affect over a third of the UK adult population and are a common reason for sick leave from work. The aims of this study were to describe the reported provision of work participation support for adults with hand and upper limb conditions by UK hand therapists, and to identify potential training needs in this area. Methods A previous survey of the Australian Hand Therapy Association was adapted for the UK. The electronic questionnaire was distributed to members of the British Association of Hand Therapists. Eligible individuals were UK-based occupational therapists or physiotherapists whose role included the assessment and/or treatment of patients ≥18 years with hand or upper limb issues. Results There were 123 participants (17% response rate). The most frequently reported work participation interventions were discussing graded return to work and sign-posting patients to speak with their doctor. The Allied Health Professionals Health and Work Report and Fit Note were not regularly used, and respondents reported low levels of confidence in issuing these documents. Barriers to providing work recommendations included a perceived lack of time, skills, knowledge and training. Facilitators included the patient discussing work as a rehabilitation goal. Conclusion Development opportunities for UK hand therapists include increasing patient awareness that they can ask for work-related advice and documentation, promoting existing health and work training, developing hand therapy-specific resources, and ensuring access to electronic Fit Notes. International opportunities include the continuation of this survey with a focus on generating exemplar work participation strategies to inform further research.
Use of family planning information by primary healthcare clinic managers in South Africa
Authors: Moloko Sophy Mogatlogedi , Ramukumba Mokholelana Margaret 
Published: March 2024

Background: Routine family planning data in South Africa are managed using a routine health information system, which facilitates data collection, storage, processing, presentation and dissemination. Healthcare providers generate data daily as they carry out their duties. The information generated should be used for planning and evaluating health program performance and policy development. Objective: To explore the use of family planning information by primary healthcare (PHC) clinic managers in South Africa. Method: A qualitative descriptive exploratory study was carried out in 11 PHC clinics in Tshwane District. Individual semi-structured interviews were conducted with 11 clinic managers. The data were analysed using a thematic analysis approach. Results: Managers used the information to disseminate performance and feedback, monitor the program’s performance and make decisions to improve the family planning service. However, they experienced challenges that hampered the effective use of the information. Conclusion: The use of family planning information is critical for improving the performance of the program. The clinics need sufficient skilled healthcare providers who are able to provide comprehensive family planning and generate accurate and reliable information that can be used to improve the service. Collaboration between the private and public sectors is critical in monitoring the program’s performance.
Surgical treatment for congenital vertebral anomalies with bilateral bifid intrathoracic rib in association: A series of five cases
Authors: Zhang Hanwen , Zhu Lining , Jiao Jiahao , Guo Dong , Zhang Xuejun , Yao Ziming 
Published: March 2024

Background: Congenital scoliosis is often associated with costal deformities, of which a bilateral bifid intrathoracic rib is very rare. The aim of this study was to retrospectively summarize the clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcomes of five patients with bilateral bifid intrathoracic rib. Methods: We retrospectively reviewed the imaging findings and medical records of five pediatric patients (two girls, three boys) with bilateral bifid intrathoracic rib who were surgically treated for congenital kyphoscoliosis (mean age = 8 years). The clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcome were summarized. Results: Four of five patients showed abnormalities from birth. All five patients presented with kyphoscoliosis and a fused vertebral body or lamina. The bilateral bifid intrathoracic rib was located at T2–3 in three patients, T7 in one patient, and T10 in one patient. Various congenital spinal deformities and multiple system malformations were present in all five patients. Three patients had preoperative neurological deficits. For corrective surgery, one patient received a traditional growing rod implantation, one patient underwent resection of a bony septum, and three patients underwent spinal osteotomy. One patient suffered complete paralysis of the lower limbs after surgery. Conclusion: Bilateral bifid intrathoracic rib is a rare anomaly that typically occurs in patients with serious kyphoscoliosis. Bilateral bifid intrathoracic rib patients show similar clinical and radiological characteristics and are likely to exhibit neurological deficits before or following corrective surgery. Spinal surgeons should be aware of the high risk of permanent neurological complications related to surgery in these patients. Level of evidence: level IV.
A Scoping Review of Personalized, Interactive, Web-Based Clinical Decision Tools Available for Breast Cancer Prevention and Screening in the United States
Authors: Kamil Dalya , Wojcik Kaitlyn M. , Smith Laney , Zhang Julia , Wilson Oliver W. A. , Butera Gisela , Jayasekera Jinani 
Published: March 2024

Introduction. Personalized web-based clinical decision tools for breast cancer prevention and screening could address knowledge gaps, enhance patient autonomy in shared decision-making, and promote equitable care. The purpose of this review was to present evidence on the availability, usability, feasibility, acceptability, quality, and uptake of breast cancer prevention and screening tools to support their integration into clinical care. Methods. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist to conduct this review. We searched 6 databases to identify literature on the development, validation, usability, feasibility, acceptability testing, and uptake of the tools into practice settings. Quality assessment for each tool was conducted using the International Patient Decision Aid Standard instrument, with quality scores ranging from 0 to 63 (lowest-highest). Results. We identified 10 tools for breast cancer prevention and 9 tools for screening. The tools included individual (e.g., age), clinical (e.g., genomic risk factors), and health behavior (e.g., alcohol use) characteristics. Fourteen tools included race/ethnicity, but no tool incorporated contextual factors (e.g., insurance, access) associated with breast cancer. All tools were internally or externally validated. Six tools had undergone usability testing in samples including White (median, 71%; range, 9%–96%), insured (99%; 97%–100%) women, with college education or higher (60%; 27%–100%). All of the tools were developed and tested in academic settings. Seven (37%) tools showed potential evidence of uptake in clinical practice. The tools had an average quality assessment score of 21 (range, 9–39). Conclusions. There is limited evidence on testing and uptake of breast cancer prevention and screening tools in diverse clinical settings. The development, testing, and integration of tools in academic and nonacademic settings could potentially improve uptake and equitable access to these tools. Highlights There were 19 personalized, interactive, Web-based decision tools for breast cancer prevention and screening. Breast cancer outcomes were personalized based on individual clinical characteristics (e.g., age, medical history), genomic risk factors (e.g., BRCA1/2), race and ethnicity, and health behaviors (e.g., smoking). The tools did not include contextual factors (e.g., insurance status, access to screening facilities) that could potentially contribute to breast cancer outcomes. Validation, usability, acceptability, and feasibility testing were conducted mostly among White and/or insured patients with some college education (or higher) in academic settings. There was limited evidence on testing and uptake of the tools in nonacademic clinical settings.
A lineage-specific STAT5BN642H mouse model to study NK-cell leukemia
Authors: Klein Klara , Kollmann Sebastian , Hiesinger Angela , List Julia , Kendler Jonatan , Klampfl Thorsten , Rhandawa Mehak , Trifinopoulos Jana , Maurer Barbara , Grausenburger Reinhard , Betram Christof A. , Moriggl Richard , Rülicke Thomas , Mullighan Charles G. , Witalisz-Siepracka Agnieszka , Walter Wencke , Hoermann Gregor , Sexl Veronika , Gotthardt Dagmar 
Published: March 2024

Abstract
Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK). All N642Hvav/+ mice rapidly develop an aggressive T/NKT-cell leukemia, whereas N642HNK/NK mice display an indolent NK-large granular lymphocytic leukemia (NK-LGLL) that progresses to an aggressive leukemia with age. Samples from patients with NK-cell leukemia have a distinctive transcriptional signature driven by mutant STAT5B, which overlaps with that of murine leukemic N642HNK/NK NK cells. To our knowledge, we have generated the first reliable STAT5BN642H-driven preclinical mouse model that displays an indolent NK-LGLL progressing to aggressive NK-cell leukemia. This novel in vivo tool will enable us to explore the transition from an indolent to an aggressive disease and will thus permit the study of prevention and treatment options for NK-cell malignancies.
Interactions between integrin α9β1 and VCAM-1 promote neutrophil hyperactivation and mediate poststroke DVT
Authors: Pandey Nilesh , Kaur Harpreet , Chorawala Mehul R. , Anand Sumit Kumar , Chandaluri Lakshmi , Butler Megan E. , Aishwarya Richa , Gaddam Shiva J. , Shen Xinggui , Alfaidi Mabruka , Wang Jian , Zhang Xiaolu , Beedupalli Kavitha , Bhuiyan Md. Shenuarin , Bhuiyan Mohammad Alfrad Nobel , Buchhanolla Prabandh , Rai Prashant , Shah Rahul , Chokhawala Himanshu , Jordan J. Dedrick , Magdy Tarek , Orr A. Wayne , Stokes Karen Y. , Rom Oren , Dhanesha Nirav 
Published: March 2024

Abstract
Venous thromboembolic events are significant contributors to morbidity and mortality in patients with stroke. Neutrophils are among the first cells in the blood to respond to stroke and are known to promote deep vein thrombosis (DVT). Integrin α9 is a transmembrane glycoprotein highly expressed on neutrophils and stabilizes neutrophil adhesion to activated endothelium via vascular cell adhesion molecule 1 (VCAM-1). Nevertheless, the causative role of neutrophil integrin α9 in poststroke DVT remains unknown. Here, we found higher neutrophil integrin α9 and plasma VCAM-1 levels in humans and mice with stroke. Using mice with embolic stroke, we observed enhanced DVT severity in a novel model of poststroke DVT. Neutrophil-specific integrin α9–deficient mice (α9fl/flMrp8Cre+/−) exhibited a significant reduction in poststroke DVT severity along with decreased neutrophils and citrullinated histone H3 in thrombi. Unbiased transcriptomics indicated that α9/VCAM-1 interactions induced pathways related to neutrophil inflammation, exocytosis, NF-κB signaling, and chemotaxis. Mechanistic studies revealed that integrin α9/VCAM-1 interactions mediate neutrophil adhesion at the venous shear rate, promote neutrophil hyperactivation, increase phosphorylation of extracellular signal-regulated kinase, and induce endothelial cell apoptosis. Using pharmacogenomic profiling, virtual screening, and in vitro assays, we identified macitentan as a potent inhibitor of integrin α9/VCAM-1 interactions and neutrophil adhesion to activated endothelial cells. Macitentan reduced DVT severity in control mice with and without stroke, but not in α9fl/flMrp8Cre+/− mice, suggesting that macitentan improves DVT outcomes by inhibiting neutrophil integrin α9. Collectively, we uncovered a previously unrecognized and critical pathway involving the α9/VCAM-1 axis in neutrophil hyperactivation and DVT.
Unveiling heterogeneity of hysteresis in perovskite thin films
Authors: Zou Zhouyiao , Qiu Haian , Shao Zhibin 
Published: March 2024

AbstractThe phenomenon of current–voltage hysteresis observed in perovskite-based optoelectronic devices is a critical issue that complicates the accurate assessment of device parameters, thereby impacting performance and applicability. Despite extensive research efforts aimed at deciphering the origins of hysteresis, its underlying causes remain a subject of considerable debate. By employing nanoscale investigations to elucidate the relationship between hysteresis and morphological characteristics, this study offers a detailed exploration of photocurrent–voltage hysteresis at the nanoscale within perovskite optoelectronic devices. Through the meticulous analysis of localized I–V curve arrays, our research identifies two principal hysteresis descriptors, uncovering a predominantly inverted hysteresis pattern in 87% of the locations examined. This pattern is primarily attributed to the energetic barrier encountered at the interface between the probe and the perovskite material. Our findings underscore the pronounced heterogeneity and grain-dependent variability inherent in hysteresis behavior, evidenced by an average Hysteresis Index value of 0.24. The investigation suggests that the localized hysteresis phenomena cannot be exclusively attributed to either photocharge collection processes or organic cation migration at grain boundaries. Instead, it appears significantly influenced by localized surface trap states, which play a pivotal role in modulating electron and hole current dynamics. By identifying the key factors contributing to hysteresis, such as localized surface trap states and their influence on electron and hole current dynamics, our findings pave the way for targeted strategies to mitigate these effects. This includes the development of novel materials and device architectures designed to minimize energy barriers and enhance charge carrier mobility, thereby improving device performance and longevity. This breakthrough in understanding the microscale mechanisms of hysteresis underscores the critical importance of surface/interface defect trap passivation in mitigating hysteretic effects, offering new pathways for enhancing the performance of perovskite solar cells.
Solid waste characteristics and management strategies at ST Theresa (STT) and Holy Cross (HC) hospitals in Chirumanzu rural District, Zimbabwe
Authors: Shabani Takunda , Mutekwa Timothy Vurayayi , Shabani Tapiwa 
Published: March 2024

AbstractManagement of solid waste from rural hospitals is among major problems affecting developing countries. This is mostly attributed to inadequate data related to quantity and quality of hospital solid waste. Similarly, information related to rural hospital solid waste characteristics and management is limited in Zimbabwe. However, SDGs complemented by Zimbabwe Vision 2030, NDS 1 advocates for sustainable solid waste management. Hence, enough data related to characteristics of solid waste from rural hospitals are required to attain sustainability. This research focuses on hospital solid waste characteristics and management strategies at STT and HC rural hospitals. Descriptive cross sectional research design which triangulates qualitative and quantitative paradigms was utilized. Interviews, observations, questionnaires were used to collect data. Quantitative data were analyzed using Statistical Package for Social Sciences whereas qualitative data were subjected to content analysis. Solid waste generated at STT encompasses non-hazardous (77.35%), hazardous waste (22.65%). At HC solid waste consists of non-hazardous (79%) and hazardous waste (21%). Respondents at STT (70.4%) and HC (72.7%) noted that solid waste was increasing. Solid waste was increasing due to various factors namely high use of disposable materials at HC (35.1%), STT (42.5%) and increase of patients at HC (30%) and STT (29.7%). Solid waste was indiscriminately stored in various types of containers although pedal operated bins and sharp containers were highly used at STT (72.4%) and HC (69.1%). Waste receptacles were transported to disposal sites using wheelbarrows and manual handling. Open pits and burning were among disposal strategies but incineration was regarded as the golden approach at STT (44.8%) and HC (41.8%). Inappropriate hospital solid waste management was due to shortage of finance at STT (38.1%) and HC (30.9%) and unawareness among health workers. Although it was worsened by lack of all stakeholder participation at STT (79.0%) and HC (76.4%). Consequently, the study recommended application of strategies which support circular economy, integrated approach, raising awareness of health workers and provision of enough resources to rural hospitals.