bluuebunny/crossref_metadata_2025_split huggingface dataset:
How are motivational interviewing techniques associated with US healthcare employees’ mental health help-seeking behaviours when using the interactive screening programme
Authors: Frey Jodi Jacobson , Deng Yali , Osteen Philip J , Imboden Rachel , Mosby Amanda , Ware Orrin , Bazell Alicia , Phillips Danielle 
Published: December 2024

IntroductionSuicide rates for healthcare workers, coupled with mental health challenges, continue to increase in the USA. This study aimed to assess how the Interactive Screening Programme (ISP) is being used by US healthcare employees and how ISP counsellors’ use of motivational interviewing (MI) techniques was associated with employee help-seeking outcomes.MethodsWe used a retrospective one-group study to analyse secondary deidentified ISP interactive counselling dialogue (written communications between the ISP counsellor and ISP user) (time frame 2009–2019) from 5922 healthcare employees at 15 US workplaces. Help-seeking outcomes included referral requests, commitment to mental health services and improved willingness to seek mental health services. Key exposures included counsellors’ use of MI techniques.Results45% of ISP users scored in high distress on their ISP screening. Among ISP users in high distress, over 25% engaged in ISP dialogue and 63% of those who engaged in dialogue requested a referral. Bivariate analysis showed ISP users more likely to request referrals included women, younger employees, those with higher distress levels and those not currently receiving mental health services. Counsellors’ use of the MI technique, asking questions, was associated with approximately three times the odds of requesting referral (OR=3.12, p<0.001), higher odds of service commitment (OR=2.18, p<0.001) and improved willingness towards services (OR=2.21, p<0.001), compared with no questions asked during ISP dialogue. Asking questions also demonstrated a large effect size for all three dependent variables.ConclusionResults support the use of the MI techniques, especially asking questions, with ISP dialogue to encourage healthcare employees’ mental health help-seeking.
GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth
Authors: Mohamedali Khalid A , Aguirre Brian , Lu Cheng-Hsiang , Chandla Anubhav , Kejriwal Nidhi , Liu Lucia , Chan Ann M , Cheung Lawrence H , Kok SuYin , Duarte Sergio , Alvarez de Cienfuegos Ana , Casero David , Rosenblum Michael G , Wadehra Madhuri 
Published: December 2024

BackgroundGranzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. Fusion proteins and immunoconjugates represent an innovative therapeutic approach to specifically deliver a deadly payload to target cells. Epithelial membrane protein-2 (EMP2) is highly expressed in invasive breast cancer (BC), including triple-negative BC (TNBC), and represents an attractive therapeutic target.MethodsWe designed a novel fusion protein (GrB-Fc-KS49) composed of an active GrB fused to an anti-EMP2 single-chain antibody tethered through the immunoglobulin G heavy chain (Fc) domain. We assessed the construct’s GrB enzymatic activity, anti-EMP2 binding affinity, and cytotoxicity against a panel of BC cells. The construct’s pharmacokinetics (PK), toxicity profile, and in vivo efficacy were also evaluated.ResultsGrB-Fc-KS49 exhibited comparable GrB enzymatic activity to commercial GrB, as well as high affinity to an EMP2 peptide, with the dissociation constant in the picomolar range. The fusion protein rapidly internalized into EMP2+cancer cells and showed in vitro cytotoxicity to cell lines expressing surface EMP2, with half-maximal cytotoxicity (IC50) values below 100 nM for most positive lines. Ex vivo stability at 37°C indicated a half-life exceeding 96 hours while in vivo PK indicated a biexponential plasma clearance, with a moderate initial clearance (t1/2α=18.4 hours) and a much slower terminal clearance rate (t1/2β=73.1 hours). No toxicity was measured in a Chem16 panel between the control and the GrB-Fc-KS49. In vivo, the GrB-Fc-KS49 showed efficacy against a TNBC syngeneic (4T1/FLuc) mouse model, reducing tumor volume and cell proliferation and increasing cell death compared with controls. Treatment using an EMT6 mouse model confirmed these results. In addition to a significant impact on cell proliferation, GrB-Fc-KS49 treatment also resulted in a dramatic increase of tumor-infiltrating CD45+ cells and redistribution of tumor-associated macrophages. Transcriptomic analysis of tumors post-treatment confirmed the remodeling of the immune tumor microenvironment by the GrB-Fc-KS49 immunotoxin.ConclusionsGrB-Fc-KS49 showed high specificity and cytotoxicity towards EMP2-positive cells. In vivo, it reduced tumor burden and increased the recruitment of immune cells into the tumor, suggesting that GrB-Fc-KS49 is a promising therapeutic candidate against BC.
Neuropsychiatric manifestations following chimeric antigen receptor T cell therapy for cancer: a systematic review of clinical outcomes and management strategies
Authors: Fleischer Anna , Kurth Sophia , Duell Johannes , Topp Max , Strunz Patrick-Pascal , Mersi Julia , Rasche Leo , Sanges Carmen , Hudecek Michael , Einsele Hermann , Maatouk Imad 
Published: December 2024

BackgroundChimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative modality in the treatment of patients with cancer. However, it is increasingly evident that this therapeutic approach is not without its challenges. The unique nature of CAR-T cells as living drugs introduces a distinct set of side effects. As the application of CAR-T cell therapy expands to treat a broader range of diseases, it becomes increasingly important to devise effective strategies for handling the associated toxicities. Challenges in treating patients with CAR-T cells include addressing complications such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and cytopenias. This comprehensive review seeks to systematically identify, categorize and elucidate all previously described neurological and psychological side effects associated with CAR-T cell therapy, shedding light on the pertinent laboratory findings that underscore these phenomena.MethodsPubMed, Springer Link, and ScienceDirect were systematically searched for empirical studies on adult patients with cancer receiving CAR-T cell therapy for hemato-oncological malignancies. Quality assessment was conducted using Version 2 of the Cochrane risk-of-bias tool (RoB 2) for randomized trials and adherence to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for observational studies. The synthesis of findings was conducted via a narrative approach, consolidating the diverse array of data into a coherent framework.ResultsFrom an initial pool of 2,276 citations, 546 studies met the inclusion criteria, exhibiting a rich tapestry of heterogeneity in terms of study characteristics and patient samples. The incidence of neuropsychological symptoms varied notably across different CAR-T cell products and hematological malignancies. Among the most frequently reported neuropsychological symptoms were aphasia, attention deficits, impaired consciousness, and disorientation, alongside a constellation of other symptoms including confusion, cognitive impairment, memory loss, writing difficulties, fatigue, headache, agitation, tremor, seizures, and psychomotor retardation. Early intervention strategies, including corticosteroids and tocilizumab, have shown the potential to reduce the intensity of neuropsychological symptoms and prevent their progression to critical complications.ConclusionThese insights underscore the imperative of extending neuropsychological assessments beyond the conventional Immune Effector Cell-Associated Encephalopathy score framework.
Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity
Authors: Li Zengpeng , Li Mengyuan , Yang Liu , Chen Jie , Ye Qian , Qian Wenbin , Wang Shibing 
Published: December 2024

ObjectiveTargeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immunosuppressive tumor microenvironment (TME).MethodsTo improve therapeutic efficacy while minimizing toxicities, we engineered an oncolytic vaccinia virus (OVV) encoding an anti-CD47 nanobody (OVV-αCD47nb). We demonstrated the specific binding activity of αCD47nb secreted from the virus-infected cells to CD47 and that both secreted αCD47nb and OVV-αCD47nb blocked the “don’t eat me” signal of macrophages.ResultsIntratumorally injected OVV-αCD47nb continuously releases the αCD47nb in tumor tissues, thereby conferring superior systemic activity against breast and colon tumor cells and prolonging survival compared with OVV control. Furthermore, treatment with OVV-αCD47nb also remodeled the TME, as shown by increased T cell infiltration, CD8+T cell activation and tumor-associated macrophages polarization, significantly enhancing innate and adoptive immunity. Additionally, the inclusion of programmed cell death protein-1 inhibiting boosted the anticancer efficacy of OVV-αCD47nb and raised the full response rate in tumor-bearing animals.ConclusionOverall, our findings highlight the therapeutic potential of OVV-αCD47nb for breast and colon cancer, and demonstrate its ability to modulate the immune cell profiles within tumors. This has established a rationale for further exploring OVV-αCD47nb as a potential therapy in the clinic.
CAR-T cell therapy in developing countries: how long should we wait?
Authors: Gautam Sanjivan , Gautam Balram , Shilpakar Ramila , K C Sudhamshu , Kurmi Om P 
Published: December 2024

Low- and middle-income countries (LMICs) face a significant burden of cancer prevalence and incidence. However, the survival rates for patients with cancer in these regions are notably lower than those in high-income countries, primarily due to late diagnosis and limited access to advanced treatments. Chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising outcomes in certain terminally ill patients with cancer, yet access to this treatment remains limited in LMICs, including Nepal.The Center for Regenerative Medicine in Nepal has initiated efforts to make CAR-T cell therapy accessible to patients with cancer at a substantially reduced cost. This initiative includes successful research to test the feasibility of local laboratory capabilities using reagents sourced locally or from developed countries. Additionally, a Good Manufacturing Practicies (GMP) grade CAR-T cell manufacturing facility is being established to commence clinical manufacturing. This endeavor has encountered several challenges, including technical difficulties, regulatory barriers, and resource limitations, which could provide valuable insights for other developing countries. This experience from Nepal highlights the importance of interdisciplinary collaboration, shared knowledge, funding, and innovative solutions from the global scientific community to achieve equitable access to advanced medical treatments.
Krebs von den Lungen-6 surveillance in immune checkpoint inhibitor-induced pneumonitis
Authors: Matsukane Ryosuke , Nakamura Shoji , Minami Haruna , Tsubouchi Kazuya , Yoneshima Yasuto , Hata Kojiro , Yasukochi Sai , Suetsugu Kimitaka , Okamoto Isamu , Hirota Takeshi 
Published: December 2024

BackgroundThe immune-related adverse event (irAE), pneumonitis, is a potentially fatal complication of immune checkpoint inhibitors (ICIs). Preventing its progression is crucial, emphasizing the need for effective screening tests. We evaluated the feasibility of using Krebs von den Lungen-6 (KL-6), a marker for interstitial pneumonitis, as a screening tool for pneumonitis.MethodsWe examined 500 patients with cancer divided into two groups: those with cancer other than non-small cell lung cancer (NSCLC) (Group 1, n=382) and those with NSCLC (Group 2, n=118). KL-6 levels were monitored before and during ICI treatment and analyzed for their correlation with pneumonitis.ResultsIn Group 1, 37 patients (9.7%) developed pneumonitis. KL-6 levels were significantly elevated at irAE onset (pre: 222.0 U/mL, post: 743.0 U/mL, p<0.0001). Receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.903 (sensitivity 81.1%, specificity 91.6%) with a cut-off value 1.52 times pre-KL-6 levels, indicating that KL-6 is a reliable biomarker for pneumonitis. In these patients, the KL-6 level increased regardless of pneumonitis severity and was significantly elevated in patients with both symptomatic (pre: 205.0 U/mL, post: 674.5 U/mL, p<0.0001) and asymptomatic pneumonitis (pre: 314.0 U/mL, post: 743.0 U/mL, p<0.0001) at irAE onset. After irAE treatment, KL-6 levels in steroid-responsive patients remained unchanged; however, steroid-unresponsive patients had a significant increase in KL-6 levels at 1 month (1078 U/mL, p=0.031) compared with at irAE onset (678.0 U/mL). In Group 2, 24 patients (20.3%) developed irAE pneumonitis, with KL-6 levels elevated (pre: 360.5 U/mL, post: 506.5 U/mL, p=0.029) and an AUC of 0.683, indicating that KL-6 was less reliable in patients with NSCLC.ConclusionsKL-6 is a viable screening biomarker in ICI-induced pneumonitis, particularly in patients without NSCLC. In patients with NSCLC, the significance of KL-6 monitoring is limited as it is not effective for detecting ICI-induced pneumonitis; their treatment is typically managed by pulmonary specialists. Early detection through KL-6 monitoring facilitates timely intervention for ICI-induced pneumonitis, potentially preventing treatment interruptions and reducing the need for immunosuppressants.
Heavy-quark dominance and fine structure of excited heavy baryons $$\Sigma _{Q}$$, $$\Xi '_{Q}$$ and $$\Omega _{Q}$$
Authors: Li Zhen-Yu , Yu Guo-Liang , Wang Zhi-Gang , Gu Jian-Zhong 
Published: December 2024

Abstract
In the framework of the relativized quark model, the calculation of spin-orbit interactions is improved by considering the contribution from the light-quark cluster in a singly heavy baryon. It modifies the energy level splitting of the orbital excitation significantly and causes the emergence of fine structures for

$$\Sigma _{Q}$$

Σ
Q

,

$$\Xi '_{Q}$$

Ξ
Q
′

and

$$\Omega _{Q}$$

Ω
Q

baryons. Based on this improvement, we systematically analyze the fine structures and retest the heavy quark dominance mechanism. This mechanism is found to be violated in the 1P-wave states of the

$$\Sigma _{c}$$

Σ
c

,

$$\Xi '_{c}$$

Ξ
c
′

and

$$\Omega _{c}$$

Ω
c

baryons although it remains effective overall, which may help to understand the nature of the heavy quarks and strong interactions. With the predicted fine structures, we make the precise assignments of those observed heavy baryons which once could not be accurately explained due to their close mass values. The method used in this work is instructive and applicable for the study of more complex exotic hadrons, such as the heavy tetraquarks and pentaquarks.
Effects of Transcutaneous Electrical Acupoint Stimulation on the Incidence of Hypoxia in Elderly Patients Undergoing Painless Gastrointestinal Endoscopy: A Randomized Controlled Trial
Authors: Zhou Wenyu , Wang Yu , Ye Pengcheng , Hu Song , Li Siyu , Wang Mingxia , Sheng Duanyang , Chen Yuanli , Shen Wang , Zhang Yi , Liu Feng , Zhang Wei , Lv Xin , Wang Xiangrui , Yang Hao 
Published: December 2024

Background: Hypoxia is not uncommon in elderly patients during painless gastrointestinal endoscopy. This study aimed to determine the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in reducing the occurrence of hypoxia symptoms in elderly patients.Methods: Patients were randomly and equally grouped into sham control (n = 109) or TEAS group (n = 109) by using the random number table method. Patients in the TEAS group received electrical stimulation at the bilateral ST36 points 30 min before the examination until the end of the painless gastrointestinal endoscopy. Patients in the control group only had electrodes attached to bilateral nonacupoints in a similar pattern as the TEAS group without electrical stimulation. The primary endpoints measured were the incidence of hypoxia and severe hypoxia. The secondary endpoints included propofol dosage, sedation‐related adverse events, hemodynamic parameters, surgical duration, patient recovery time, pain score, patient satisfaction, anesthesiologist satisfaction, and endoscopist satisfaction.Results: Of the 251 patients who participated in this study, 218 patients ended up completing the final study. The primary outcome was that, compared with group control, the incidence of hypoxia in group TEAS was reduced by 11% (19.3% vs. 8.3%, p = 0.018) and the incidence of severe hypoxia did not show a significant change (7.3% vs. 2.8%, p = 0.122). And there was a significant decrease in the occurrence of patients requiring emergency airway assistance (increased oxygen flow: 16.5% vs. 6.4%, p = 0.019, jaw thrust: 11.0% vs. 3.7%, p = 0.038, mask‐assisted ventilation: 5.5% vs. 1.8%, p = 0.015).Conclusion: TEAS can reduce the incidence of hypoxia in elderly patients undergoing painless gastrointestinal endoscopy.Trial Registration: ClinicalTrials.gov identifier: ChiCTR2200059465.
Real time hand gesture detection by using convolutional neural network for in-vehicle infortainment systems
Authors: Yaakob Wan Bejuri Wan Mohd , Asmai Siti Azira , Ikram Raja Rina Raja , Rahim Nur Raidah , Khambari Najwan , Azmi Mohd Sanusi , Sholva Yus 
Published: December 2024

Nowadays, <span>a variety of technologies on autonomous vehicles have been extensively developed, including in-vehicle infotainment (IVI). It have been noted as one of the key services in the automobile industry. In the near future, people will be able to watch some virtual reality (VR) movies through the streaming service provided in the vehicle. However, a person sometime not tend to be joy while watching espcially when the remote controller or audio sensory controller lack of battery or too far from IVI panel. Thus, the purpose of this research is to design a scheme of real time hand gesture detection for in-vehicle infotainment system, in order to create human computer experience. In this research, the image of human palm hand will be taken by using camera for recognize the hand gesture action. This proposed scheme will recognize human gesture and convert to be computer intruction, that can be understood by IVI device. As a result, it show our proposed scheme can be the most consistent in term of accuracy and loss compared to others method. Overall, this research represents a significant step toward improving better user experience. Furthermore, the proposed scheme is anticipated to contribute significantly to the IVI field, benefiting both academia and societal outcomes.</span>
Ritual Deposit at Bir Nurayet: Fertility Cult at the Foot of Gebel Magardi, Sudan
Authors: Jórdeczka Maciej , Bobrowski Przemysław , Chłodnicki Marek 
Published: December 2024

Abstract
Bir Nurayet is a place in the Red Sea Hills at the foot of Jebel Magardi. One of the most significant rock art galleries on the African continent exists near this beautiful isolated mountain. In 2010, a stone chest was discovered in one of the valleys, containing a deposit of several dozen clay figurines, mostly phallic-shaped with a few representations of animals, miniature vessels and their fragments, as well as bronze products. Thanks to the radiocarbon date obtained from charcoal, the chronology of the collection was set in the second half of the 6th century AD. The discovery of votive goods is of great value – it allows us to look into the very obscure sphere of rituals of the Blemmyean community that inhabited these areas at that time. Without a doubt, we are dealing here with one of the manifestations of the fertility cult, which was common in the past in many different versions.
Advancing Topological Interlocking Structures: Recent Developments, Applications, and Challenges in Civil Engineering
Authors: Tavoosi Gazkoh Maliheh , Lin Xiaoshan , Zhou Annan 
Published: December 2024

AbstractTopological interlocking structures have garnered significant attention for their distinctive properties, including robust resistance to crack propagation, outstanding energy absorption, adaptable flexibility, high resistance to missing elements and easy assembly and disassembly. Moreover, integrating various materials into a single structure enables versatile design possibilities. This paper comprehensively reviews recent research on topological interlocking elements and structures, encompassing element designs, manufacturing techniques and engineering applications. Furthermore, it explores the performance of topological interlocking structures, covering aspects such as fracture resistance, structural integrity, bending flexibility, ease of assembly and disassembly and energy absorption. While topological interlocking elements offer various benefits, challenges remain in their broader implementation, particularly as structural members in civil engineering structures. This paper engages in a critical discussion of existing research gaps and outlines directions for future research.
Adequate post-ischemic reperfusion of the mouse brain requires endothelial NFAT5
Authors: Kunze Reiner , Wacker Paul , Breuer Paula , Nasyrov Emil , Kur Ivan M. , Weigert Andreas , Wagner Andreas H. , Marti Hugo H. , Korff Thomas 
Published: December 2024

AbstractSeverity and outcome of strokes following cerebral hypoperfusion are significantly influenced by stress responses of the blood vessels. In this context, brain endothelial cells (BEC) regulate inflammation, angiogenesis and the vascular resistance to rapidly restore perfusion. Despite the relevance of these responses for infarct volume and tissue recovery, their transcriptional control in BEC is not well characterized. We revealed that oxygen and nutrient-deprived BEC activate nuclear factor of activated T-cells 5 (NFAT5)—a transcription factor that adjusts the cellular transcriptome to cope with environmental stressors. We hypothesized that NFAT5 controls the expression of genes regulating the response of BEC in the ischemic brain. The functional relevance of NFAT5 was assessed in mice, allowing the conditional EC-specific knock-out of Nfat5 (Nfat5(EC)−/−). Cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) followed reperfusion up to 28 days. While loss of endothelial Nfat5 did not evoke any phenotypic abnormalities in mice under control conditions, infarct volumes, neurological deficits and the degree of brain atrophy were significantly pronounced following MCAO as compared to control animals (Nfat5fl/fl). In contrast, MCAO-induced edema formation, inflammatory processes and angiogenesis were not altered in Nfat5(EC)−/− mice. RNAseq analyses of cultured BEC suggested that loss of NFAT5 impairs the expression of Kcnj2 encoding a potassium channel that may affect reperfusion. In fact, lower levels of KCNJ2 were detected in arterial endothelial cells of Nfat5(EC)−/− versus Nfat5fl/fl mice. Laser speckle contrast imaging of the brain revealed an impaired perfusion recovery in Nfat5(EC)−/− versus Nfat5fl/fl mice after MCAO.Collectively, NFAT5 in arterial BEC is required for an adequate reperfusion response after brain ischemia that is presumably dependent on the maintenance of Kcnj2 expression. Consequently, impairment of the protective role of endothelial NFAT5 results in enlarged infarct sizes and more severe functional deficits of brain functions.