bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning in Spine Oncology: A Narrative Review
Authors: Wilson Seth B. , Ward Jacob , Munjal Vikas , Lam Chi Shing Adrian , Patel Mayur , Zhang Ping , Xu David S. , Chakravarthy Vikram B.
Published: June 2024

Study Design

Narrative Review.

Objective

Machine learning (ML) is one of the latest advancements in artificial intelligence used in medicine and surgery with the potential to significantly impact the way physicians diagnose, prognose, and treat spine tumors. In the realm of spine oncology, ML is utilized to analyze and interpret medical imaging and classify tumors with incredible accuracy. The authors present a narrative review that specifically addresses the use of machine learning in spine oncology.

Methods

This study was conducted in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) methodology. A systematic review of the literature in the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases since inception was performed to present all clinical studies with the search terms ‘[[Machine Learning] OR [Artificial Intelligence]] AND [[Spine Oncology] OR [Spine Cancer]]’. Data included studies that were extracted and included algorithms, training and test size, outcomes reported. Studies were separated based on the type of tumor investigated using the machine learning algorithms into primary, metastatic, both, and intradural. A minimum of 2 independent reviewers conducted the study appraisal, data abstraction, and quality assessments of the studies.

Results

Forty-five studies met inclusion criteria out of 480 references screened from the initial search results. Studies were grouped by metastatic, primary, and intradural tumors. The majority of ML studies relevant to spine oncology focused on utilizing a mixture of clinical and imaging features to risk stratify mortality and frailty. Overall, these studies showed that ML is a helpful tool in tumor detection, differentiation, segmentation, predicting survival, predicting readmission rates of patients with either primary, metastatic, or intradural spine tumors.

Conclusion

Specialized neural networks and deep learning algorithms have shown to be highly effective at predicting malignant probability and aid in diagnosis. ML algorithms can predict the risk of tumor recurrence or progression based on imaging and clinical features. Additionally, ML can optimize treatment planning, such as predicting radiotherapy dose distribution to the tumor and surrounding normal tissue or in surgical resection planning. It has the potential to significantly enhance the accuracy and efficiency of health care delivery, leading to improved patient outcomes.
Job Autonomy and Employee Psychological Well-being: The Mediating Effect of Employee Voice
Authors: Sharma Aarti , Sharma Himani
Published: June 2024

The review of employee well-being literature in the context of human resource management and organisational behaviour advocates that well-being is a major area of consideration for every organisation. Thus, based on job demand resource (JDR) theory, the study aims to examine the influence of job autonomy on the psychological well-being of employees with promotive voice behaviour playing the role of a mediator. Structural equation modelling (SEM) is used to analyse the cross-sectional data of 206 employees from the Indian service sector. The findings support the direct relationship between job autonomy, employee promotive voice and psychological well-being and further confirm the mediating role of promotive voice between job autonomy and psychological well-being. This study suggests that organisations should delegate authority to their employees to carry out their job roles, as it can improve their voice behaviour and further their psychological well-being. To the best of our knowledge, this is the first study to investigate the mediating effect of promotive voice behaviour between job autonomy and psychological well-being.
Cyber Shadows over Nuclear Peace: Understanding and Mitigating Digital Threats to Global Security
Authors: Jung Yujin J.
Published: June 2024

This article examines the intersection of cyber warfare and nuclear security, emphasising the significance of addressing the emerging threats to nuclear facilities from cyberattacks. The article highlights a gap in the international security architecture: the absence of an international regime for nuclear cybersecurity. This deficiency challenges the Non-Proliferation Treaty regime, threatening global peace and stability by undermining the treaty’s objectives and increasing the risk of nuclear proliferation and misuse. The research underscores the need for an international regime that integrates cybersecurity with nuclear security. It calls for the involvement of middle powers in international negotiations and consensus-building, alongside exploring innovative diplomatic strategies and robust legal frameworks. The article seeks to contribute to the discourse on international security, advocating for a coordinated global response to safeguard against the catastrophic consequences of digital threats in the nuclear domain.
Evaluation of a New Integrative Health and Wellness Clinic for Veterans at the San Francisco VA Health Care System: A Mixed-Methods Pilot Study
Authors: Nicosia Francesca M , Purcell Natalie , Bertenthal Dan , Usman Hajra , Seidel Ilana , McGrath Sarah , Hildebrand Caitlin , McCarthy Brittan , Seal Karen H
Published: June 2024

Objective

The Integrative Health and Wellness Clinic (IHWC), established in 2019 at the San Francisco VA Health Care System, is an interdisciplinary clinic consisting of a medical provider, dietician, physical therapist, and psychologist trained in complementary and integrative health (CIH) following the VA Whole Health model of care. Veterans with complex chronic conditions seeking CIH and nonpharmacologic approaches are referred to the IHWC. This study evaluated the clinic’s acceptability and feasibility among veteran patients and its preliminary impact on health and wellbeing, health-related goals, and use of CIH approaches.

Methods

Mixed methods were used to assess patient-reported outcomes and experiences with the IHWC. Participants completed surveys administered at baseline and 6-months and a subset completed a qualitative interview. Pre- and post-scores were compared using t-tests and chi-square tests.

Results

Thirty-five veterans completed baseline and 6-month follow up surveys. Of these, 13% were women; 24% < 50 years of age, and 44% identified as racial/ethnic minorities. Compared to baseline, at 6 months, there were significant ( P < .05) improvements in overall health, physical health, perceived stress, and perceived helpfulness of clinicians in assisting with goal attainment; there was a trend toward improved mental health ( P = .057). Interviews (n = 25) indicated satisfaction with the interdisciplinary clinical model, support of IHWC providers in goal attainment, and positive impact on physical and mental health. Areas for improvement included logistics related to scheduling of multiple IHWC providers and referrals to other CIH services.

Conclusion

Results revealed significant improvement in important clinical domains and satisfaction with interprofessional IHWC clinic providers, but also opportunities to improve clinic processes and care coordination. An interdisciplinary clinic focused on CIH and Whole Health is a feasible and acceptable model of care for veterans with complex chronic health conditions in the VA healthcare system.
Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants
Authors: Gui Meilin , He Miao , Qin Lixia
Published: June 2024

Background

Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon.

Case presentation

In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient's symptoms deteriorated rapidly following a COVID-19 infection.

Conclusions

In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it's extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.
Safety and efficacy of multi-target TKI combined with nivolumab in check-point inhibitor-refractory patients with advanced NSCLC: a prospective, single-arm, two-stage study
Authors: Zhang Bo , Liu Hongyu , Shi Chunlei , Gao Zhiqiang , Zhong Runbo , Gu Aiqin , Chu Tianqing , Wang Huimin , Xiong Liwen , Zhang Wei , Zhang Xueyan , Yan Bo , Teng Jiajun , Wang Weimin , Bai Hao , Qiao Rong , Cheng Lei , Kuang Yanbin , Zhao Ruiying , Zhong Hua , Han Baohui
Published: June 2024

Background

Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs.

Methods

This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively.

Results

Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively.

Conclusion

Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted.

Trial registration

NCT04507906 August 11, 2020.
Diagnostic performance of Node Reporting and Data System (Node-RADS) for assessing mesorectal lymph node in rectal cancer by CT
Authors: Niu Yue , Wen Lu , Yang Yanhui , Zhang Yi , Fu Yi , Lu Qiang , Wang Yu , Yu Xiao , Yu Xiaoping
Published: June 2024

Background

To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment.

Methods

Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated.

Results

Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05).

Conclusions

The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.
Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis
Authors: El Zein Lulwa , Smith Wendy M. , White Launia J. , Hodge David O. , Olsen Timothy W. , Pulido Jose S. , Dalvin Lauren A.
Published: June 2024

Background

Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides.

Methods

Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022.

The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included.

Results

There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis.

Conclusion

OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.
Collaboration in the return-to-work process after sick leave due to common mental disorders: a qualitative study of stakeholders’ views on goals and roles
Authors: Svärd Veronica , Arapovic Johansson Zana , Holmlund Lisa , Hellman Therese , Kwak Lydia , Björk Brämberg Elisabeth
Published: June 2024

Background

This study explores how the goals of collaboration in the return-to-work (RTW) process for people with common mental disorders are described by the stakeholders involved, and how they experience stakeholders’ roles and responsibilities in relation to these goals.

Methods

Interviews were conducted with 41 participants from three Swedish regions. Nine of the participants were workers, six employer representatives, four occupational health professionals, four social insurance officers, 18 RTW coordinators and five physicians. Thematic analysis was conducted.

Results

Three main themes and overarching goals when collaborating on RTW were identified. In the first theme, ‘creating an informative environment’, all stakeholders emphasised clear roles and responsibilities. The second theme, ‘striving for consensus in an environment of negotiations’, addressed negotiations about when and how to collaborate, on what and with whom, and reveal different views on stakeholders’ goals, roles and responsibilities in collaboration. The third theme identified goals for ‘creating a supportive environment’ for both workers and other stakeholders. Coordinators are found to have an important role in achieving a supportive environment, and in neutralising power imbalances between workers and their employers and social insurance officers.

Conclusions

Competing goals and priorities were identified as hindering successful collaboration, contributing to a spectrum of complex versus easy RTW collaboration. This study suggests some basic conditions for achieving a collaborative arena that is neutral in terms of power balance, where all stakeholders can share their views.
Examination of learning ability development through the implementation of the “autonomy-collaboration” learning mode grounded in evidence-based medicine practice
Authors: Li Xiao-Huan , Zhang Qing , Li Chun , Yin Ya-Lei , Yang Zhen , Fu Ying , Yuan Xiao-Lin
Published: June 2024

Objective

Currently, there are still some shortcomings in EBM education in China.The study aimed to investigate the effectiveness of the novel evidence-based medicine (EBM) learning model of “autonomy-collaboration.”

Methods

A total of 91 undergraduate students majoring in clinical medicine at Zhongshan Clinical College of Dalian University from the 2019 batch were selected as the participants in this study. They were instructed to follow the EBM learning model of “autonomy-collaboration.” Upon completion of the course, questionnaires, records of participants’ sentiments and insights, and evidence-based clinical practice reports were used as indicators to evaluate the effectiveness of the training.

Results

This learning modality effectively enhanced independent learning ability of the students, stimulated their interest in learning, and strengthened the communication between students and teachers, thereby improving the quality of teaching.

Conclusion

The novel EBM learning model of “autonomy-collaboration,” exhibited robust effectiveness in instruction and facilitated the seamless integration of theoretical knowledge with clinical practice. Consequently, its widespread adoption is strongly recommended.
Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation
Authors: Babendreyer Aaron , Kieselhorst Julia , Rinkens Cindy , Lyashenko Anastasia M. , Düsterhöft Stefan , Jahr Holger , Craveiro Rogerio B. , Wolf Michael , Ludwig Andreas
Published: June 2024

Bone resorption is driven through osteoclast differentiation by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-Β ligand (RANKL). We noted that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 are downregulated at the expression level during osteoclast differentiation of the murine monocytic cell line RAW264.7 in response to RANKL. Both proteinases are well known to shed a variety of single-pass transmembrane molecules from the cell surface. We further showed that inhibitors of ADAM10 or ADAM17 promote osteoclastic differentiation and furthermore enhance the surface expression of receptors for RANKL and M-CSF on RAW264.7 cells. Using murine bone marrow-derived monocytic cells (BMDMCs), we demonstrated that a genetic deficiency of ADAM17 or its required regulator iRhom2 leads to increased osteoclast development in response to M-CSF and RANKL stimulation. Moreover, ADAM17-deficient osteoclast precursor cells express increased levels of the receptors for RANKL and M-CSF. Thus, ADAM17 negatively regulates osteoclast differentiation, most likely through shedding of these receptors. To assess the time-dependent contribution of ADAM10, we blocked this proteinase by adding a specific inhibitor on day 0 of BMDMC stimulation with M-CSF or on day 7 of subsequent stimulation with RANKL. Only ADAM10 inhibition beginning on day 7 increased the size of developing osteoclasts indicating that ADAM10 suppresses osteoclast differentiation at a later stage. Finally, we could confirm our findings in human peripheral blood mononuclear cells (PBMCs). Thus, downregulation of either ADAM10 or ADAM17 during osteoclast differentiation may represent a novel regulatory mechanism to enhance their differentiation process. Enhanced bone resorption is a critical issue in osteoporosis and is driven through osteoclast differentiation by specific osteogenic mediators. The present study demonstrated that the metalloproteinases ADAM17 and ADAM10 critically suppress osteoclast development. This was observed for a murine cell line, for isolated murine bone marrow cells and for human blood cells by either preferential inhibition of the proteinases or by gene knockout. As a possible mechanism, we studied the surface expression of critical receptors for osteogenic mediators on developing osteoclasts. Our findings revealed that the suppressive effects of ADAM17 and ADAM10 on osteoclastogenesis can be explained in part by the proteolytic cleavage of surface receptors by ADAM10 and ADAM17, which reduces the sensitivity of these cells to osteogenic mediators. We also observed that osteoclast differentiation was associated with the downregulation of ADAM10 and ADAM17, which reduced their suppressive effects. We therefore propose that this downregulation serves as a feedback loop for enhancing osteoclast development.
Reliability and reproducibility of the venous excess ultrasound (VExUS) score, a multi-site prospective study: validating a novel ultrasound technique for comprehensive assessment of venous congestion
Authors: Longino August A. , Martin Katharine C. , Leyba Katarina R. , McCormack Luke , Siegel Gabriel , Sharma Vibhu M. , Riscinti Matthew , Lopez Carolina O. , Douglas Ivor S. , Gill Edward A.
Published: June 2024

Though the novel venous excess ultrasound (VExUS) score is increasingly used as a noninvasive means of venous congestion measurement, the inter-rater reliability (IRR), inter-user reproducibility (IUR), and utility of concurrent ECG have not been evaluated. We conducted a multicenter study of the IRR, IUR, and utility of ECG for VExUS interpretation between four attending physicians of diverse specialties, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR for scans with and without ECG. Eighty-four paired VExUS exams from 42 patients, 60 of which had a concurrent ECG tracing, were interpreted. They showed substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8. There was greater agreement among images with an ECG tracing. These results suggest that ECG-augmented VExUS may be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.
Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC)
Authors: Kunz Julius Valentin , Hansmann Helena , Fähndrich Mareike , Pigorsch Mareen , Bethke Nicole , Peters Harm , Krüger Anne , Schroeder Tim , Marcy Florian , Magomedov Abakar , Müller-Redetzky Holger , Eckardt Kai-Uwe , Khadzhynov Dmytro , Enghard Philipp
Published: June 2024

Background

Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT.

Methods

We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité—Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment.

Results

From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26).

Conclusion

Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS.

Trial registration

The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.
Nutraceuticals as components of sustainable poultry production systems for food and nutrition security in Africa: a review
Authors: Mnisi Caven Mguvane , Mlambo Victor , Montso Peter Kotsoana , Manyeula Freddy , Kumanda Cebisa , Moreki John Cassius
Published: June 2024

Poultry production plays a key role in reducing food and nutrition insecurity in developing countries. However, as the poultry industry continues to grow, its future is in doubt due to economic, environmental, and social sustainability challenges. To address these challenges, poultry production practices must be optimized for food security, human health, economic viability, and environmental stewardship. At the core of this sustainability endeavour are the substantial nutritional and health requirements of birds that are raised intensively. Nutrient-dense feed resources such as maize and soybeans are indispensable in most poultry production systems in Africa, yet these grains are also direct nutrient sources for humans. This has increased their demand and prices on the world market. In addition, frequent disease outbreaks pose viability challenges that are traditionally mitigated using antibiotic growth promoters (AGPs). However, this practice has led to the undesirable propagation of antibiotic-resistant microbes and production of antibiotic residue-containing poultry products. Alternatives to AGPs such as phytogenic products are required to address some of these challenges. Phytogenics contain nutraceuticals that can boost feed efficiency, bird immunity, and product quality without the negative outcomes associated with AGPs, thus promoting sustainable poultry production. However, phytogenics have not been widely adopted in the poultry industry for a variety of reasons, which are interrogated in this review. The objective of this paper is to explore and evaluate the role of nutraceuticals in sustainable poultry production systems and how they can be used to enhance food and nutrition security in Africa. Optimal usage of phytogenics has the potential to sustain poultry meat and egg production as primary animal protein sources for a growing global human population, especially in developing countries.
The relationship between social media usage and loneliness among younger and older adults: the moderating effect of shyness
Authors: Wang Ya-Ling , Chen Yi-Jia , Liu Chih-Chi
Published: June 2024

Does social media alleviate or exacerbate loneliness? Past research has shown mixed results regarding the relationship between social media usage and loneliness among younger and older adults. Unlike younger individuals, older adults may decrease their loneliness through social media interactions. Additionally, previous research has indicated that the link between social media use and loneliness can vary depending on one’s shy tendency. Therefore, this study aims to explore the relationship between individuals’ social media use and loneliness while considering age and shyness tendency as moderating variables. The study employed a questionnaire survey conducted through convenience sampling, resulting in 234 valid responses from participants in Northern Taiwan. Among them, 113 were college students (aged 18 to 25, average age 19.40), and 121 were older adults (aged 50 to 82, average age 60.81). Using hierarchical regression analysis, results indicated that (1) age moderates the relationship between personal social media use and loneliness. Minimal differences were observed among younger individuals, but among older adults, increased social media usage time was associated with a significant reduction in loneliness. (2) Shyness tendency moderate the relationship between personal social media use and loneliness. Individuals with higher shyness tendency experience an increase in loneliness as their social media usage time lengthens.
Understanding climate risks to world cultural heritage: a systematic analysis and assessment framework for the case of Spain
Authors: Hu Haisheng , Hewitt Richard J.
Published: June 2024

Understanding the spatial distribution of world cultural heritage in its present-day geographical context is the foundation for the identification of and subsequent protection from key threats and vulnerabilities, particularly those arising from anthropogenic climate change. To address this challenge, we classified 45 Spanish world cultural heritage sites (WCHS) listed in the UNESCO register (as of 2023) according to type, entry date, and creation date. To establish a basis for a detailed analysis of the specific impact of climate change on the Spanish WCHS, a spatial cartographic database was developed showing the relationships between the WCHS and key geographical and climatic variables. We then used historical climate data, combined with a review of the impact mechanism of climate conditions on cultural heritage, to quantitatively evaluate the extent to which the WCHS in Spain are affected by local climate conditions from five aspects: freeze thaw cycle, thermal stress (thermoclastism), hydrodynamic scoring, corrosion, and biodegradation. Based on the above climate condition risks, we identified the five Spanish WCHS with the greatest potential climate condition risks, including Santiago de Compostela (Old Town), Pyrénées—Mont Perdu, the Roman Walls of Lugo, the Routes of Santiago de Compostela: Camino Francés and Routes of Northern Spain, and the Tower of Hercules. Additionally, based on different shared socioeconomic pathways (SSPs), we conducted a qualitative assessment of climate risk changes for WCHS in Spain under climate change. We found that the SSP1-2.6 scenario had the lowest climate risk, emphasizing the importance of achieving carbon neutrality for the protection of the WCHS. Our work translates historical climate conditions into specific climate risk levels for cultural heritage, providing data and theoretical support for effectively assessing the climate risks to Spanish WCHS.
Exploring how the metaverse of cultural heritage (MCH) influences users’ intentions to experience offline: a two-stage SEM-ANN analysis
Authors: He Tong-Liang , Qin Feng
Published: June 2024

The metaverse for cultural heritage (MCH) serves as a digital platform that enables users to access and engage with cultural heritage resources online. With the rapid expansion of cultural digitisation, many organizations have adopted the MCH to increase their impact and reach. However, empirical research is essential to substantiate the role and significance of MCH. This study examines users’ intentions to engage with MCH and their offline experiences. Using the SEM-ANN method, 989 respondents participated in an analysis framed by the NVM approach through questionnaires. The results show a dependence of users' offline experience intentions on their intentions to engage with MCH (β = 0.216, T = 7.915, P < 0.001), along with perceived benefits (β = 0.199, T = 6.576, P < 0.001) and perceived risks (β = − 0.051, T = − 2.008, P = 0.045). Results suggest that MCH has the potential to enhance offline experiences; factors such as creativity, entertainment and narrative significantly influence users' positive evaluations of MCH, while privacy data, performance ethic and negative psychology influences may reduce users' positive evaluations. These findings have important implications for cultural heritage managers, developers and designers, suggesting that the use of the metaverse can enrich the cultural heritage experience, attract a broader user base beyond offline methods, and promote the appreciation and dissemination of traditional culture.
Tumor Is Not the Only Target: Ensuring Equitable Person-Centered Supportive Care in the Era of Precision Medicine
Authors: Sedhom Ramy , Bates-Pappas Gleneara E. , Feldman Jill , Elk Ronit , Gupta Arjun , Fisch Michael J. , Soto-Perez-de-Celis Enrique
Published: June 2024

Communication in oncology has always been challenging. The new era of precision oncology creates prognostic uncertainty. Still, person-centered care requires attention to people and their care needs. Living with cancer portends an experience that is life-altering, no matter what the outcome. Supporting patients and families through this unique experience requires careful attention, honed skills, an understanding of process and balance measures of innovation, and recognizing that supportive care is a foundational element of cancer medicine, rather than an either-or approach, an and-with approach that emphasizes the regular integration of palliative care (PC), geriatric oncology, and skilled communication.
AlphaMissense performance as a classifier of germline and somatic variants of unknown significance in high-grade sarcoma.
Authors: Hassan Andrew Bassim Bassim , Wilkinson Rachael , Brown Stuart , Wallbank Richard , Surakhy Mirvat , Alves-Vasconcelos Sofia , Metz Paul , Qian Qinan , Mallon Hannah , Ren Tanya , Karia Isabel , Branford-White Harriet
Published: June 2024

11538

Background: Missense variants associated with high frequency, clinical context, splicing, penetrance and biochemical function are scored as pathogenic by ClinVar/ACMG (scores >99%/>90%). Pathogenic scores that range from this cut-point to 10% (benign) are referred to as variants of unknown significance (VUS). Alphafold2 is a deep neural network algorithm for protein structure trained on known molecular structures. It has informed AlphaMissense (AM) where the impact of every possible single missense variant in the human genome is assessed. The AM continuous pathogenicity score (roughly 0-0.35 benign, 0.36-0.55 ambiguous, 0.56-1.0 pathogenic) are claimed to have 90% accuracy based on ClinVar (based on 1,263 pathogenic and 1,263 benign variants). Methods: Here, we identified VUSs from the Oxford Sarcoma Precision Oncology real world cohort. This included the identification of somatic variants from FoundationOne Heme Sarcoma analysis of Formalin-Fixed Paraffin Embedded (FFPE) tumour samples. Germline variants were identified from whole exome sequencing (WES) (97 genes) from patient blood samples followed by analysis using GATK guidelines. All VUS identified were further analysed using AM. Results: AM reclassified the identified >1000 VUSs from 60 high grade sarcoma gene panels predominantly into benign or pathogenic, with only ~1% remaining as ambiguous. Variants reclassified as pathogenic were assessed for likelihood of pathogenicity based on scientific rationale. This involved evaluating current literature on the variant, determining evolutionary consensus of the residue, structural analysis to assess the potential function of the residue and enrichment of the variant within sarcoma patients compared to known frequencies across the population. Conclusions: In conclusion, the AM classifier dichotomises VUS to either benign or pathogenic, but this is not based on either structural or functional predictions directly. We conclude that it should not be currently used in the analysis of clinical samples seeking actionable variants but could instead stratify potential pathogenic variants for functional investigation.
Incidence of osteonecrosis of the jaw (ONJ) in the randomized non-inferiority phase III trial SAKK 96/12 REDUSE comparing denosumab (DN) administered every 4 weeks (q4w) versus every 12 weeks (q12w).
Authors: Von Moos Roger Anton Fredy , Mueller Andreas , Hayoz Stefanie , Mark Michael Thomas , Fischer Stefanie , Popescu Razvan A. , Fehr Mathias Konrad , Egger Claudine , Anchisi Sandro , Schmid Florian , Zaman Khalil , Ackermann Christoph J , Schreiber Alexander , Bützberger Priska , Uhlmann Nussbaum Catrina , Küng Marc , Schaer Corinne , Gillessen Silke , Templeton Arnoud J.
Published: June 2024

12067

Background: ONJ is a well-known adverse event of bone-modifying agents that can significantly impact quality of life. It is recognized that the risk of ONJ increases with the duration of treatment and can reach rates of up to 10%. Here, we report ONJ rates in a randomized non-inferiority phase 3 study investigating the optimal dose of DN. Methods: Patients with metastatic breast cancer (mBC) or metastatic castration resistant prostate cancer (mCRPC) (planned N=1380) were randomized 1:1 to receive DN q4w (Arm A) versus q12w (Arm B) after a 3-month induction phase with application q4w. Incidence of ONJ is a key secondary outcome of the study (NCT02051218). An oral inspection at baseline as well as before each application of DN was mandatory. In patients with risk factors for ONJ a prophylactic dentist visit was recommended. Data from patients who received at least 1 dose of DN and who were randomized at least one year before data cut-off (December 11, 2023) were included in this interim safety analysis. Since the differentiation between ONJ and tooth infection can be difficult, we also report this outcome. Results: 1271 patients with a median follow-up time of 3 years were analyzed. During the 3-month induction phase 2/1271 patients experienced an ONJ. In Arm A 48/575 (8.3%), in Arm B 32/561 (5.7%) patients experienced an ONJ. Time to first ONJ and/or tooth infection differs remarkably with a clear advantage for the 3-months arm (HR 0.67; 95% CI 0.48-0.93). Details are shown in the table. Conclusions: The observed ONJ rate of 8.3% is in line with the literature for patients who received denosumab q4w for over two years (mBC: 6.0%, mCRPC: 8.2%). Administration of DN q12w reduces the risk of ONJ and/or tooth infections substantially. The numerical difference of events to the standard arm as well as the time to first ONJ and/or tooth infection is clinically relevant with a risk reduction by 33%. Efficacy data for the primary endpoint time to first symptomatic skeletal event is eagerly awaited. Clinical trial information: NCT02051218 . [Table: see text]
Young lung cancer: Psychosocial needs assessment.
Authors: Florez Narjust , Kiel Lauren , Horiguchi Miki , Kaufman Rebekah , Haradon Danielle , Sanchez Michelle , Lederman Ruth , Voligny Emma , Nguyen Tom , McDonald Stephanie , Wilder Fatima , Pozo-Kaderman Cristina , Janne Pasi A. , Johnson Bruce E. , Partridge Ann H. , Enzinger Andrea Catherine
Published: June 2024

12104

Background: Young patients (≤50 years) with lung cancer (LC) face unique needs, including mental health and financial challenges, which are understudied to date. We report preliminary results of an ongoing cohort, prospective study exploring psychosocial needs in patients with LC, focusing on the experiences of young patients. Methods: Eligible patients (pts) were age ≥18 years old, with LC stages I-IV, receiving care at Dana-Farber Cancer Institute, and enrolled within 1 year of diagnosis. The FACT-G and COST questionnaires assessed psychosocial and financial distress, with higher scores indicating a more favorable well-being. Descriptive statistics summarized demographics, clinical characteristics, and prevalence of psychosocial needs. Results: 139 pts were enrolled from April 2023 - January 2024; 61 young pts were included in this analysis. 69% identified as female, 70% as White, 8% as Black, and 22% as another race (Table). Since LC diagnosis, 22 pts (36%) reported being diagnosed with at least one mental health condition. Of a possible total score of 108, the mean FACT-G score was 71 (SD: 20). Mean scores for physical, social, emotional, and functional subscales were 19, 22, 14, and 16 (out of 28, 28, 24, and 28), indicating significant burden in the emotional and functional domains. A majority reported feeling sad or anxious (53%, 59%), and 57% were worried about premature death. Most pts (62%) reported (somewhat-very much) having a lack of energy and nearly half reported having substantial pain and being bothered from treatment side effects (42%, 47%, respectively). Many pts were able to work and enjoy their usual recreational activities (66%, 72%, respectively). Nearly all reported receiving adequate emotional support from their family (95%) and friends (93%) and feeling comfortable discussing their LC with them (93%). When asked if they were satisfied with their sex life, 64% (35/55) stated that they were. Of a maximum score of 44, the mean COST score was 24 (SD: 12), consistent with high financial toxicity in this population. Notably, 40% of pts reported having no or only a little money to pay for treatments and 42% stated that out-of-pocket medical costs were considerably more than expected. 45% felt financially stressed and 41% were concerned about loss of employment; 47% stated that their LC caused a substantial financial hardship and 57% noted significant worry about future financial issues. Conclusions: Young pts with LC report ample financial toxicity and issues impacting physical, emotional, and functional well-being. Fewer social issues were reported. This study will help elucidate the needs of young pts with LC with the ultimate goal of mitigating the disease’s psychosocial impact. [Table: see text]
Targeting GARP–TGF-β1 with livmoniplimab plus anti–PD-1 budigalimab to remodel the immunosuppressive tumor microenvironment.
Authors: Dandamudi Durga B. , Refici Marion , Dillon Myles , Duggan Ryan , Kolahi Kevin , Sutherland Claire , Tribouley Catherine , Uziel Tamar , Chen Jack S.H.
Published: June 2024

2594

Background: Transforming growth factor (TGF)-β signaling has been shown to induce an immunosuppressive tumor microenvironment (TME) and promote tumor progression. Targeting key immune cells involved in this mechanism, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, by altering their function/depleting them is an important strategy in cancer therapeutics. Glycoprotein A repetitions predominant (GARP) is a membrane-bound receptor that complexes with latent TGF-β1 and plays a vital role in the immunosuppressive function of Tregs (1). In addition to Tregs, GARP–TGF-β1 is also expressed on other cells such as macrophages and tumor cells (2). Data from mouse models demonstrated that combined targeting of GARP–TGF-β1 and PD-1 improved antitumor effects compared with anti–PD-1 alone (3). Livmoniplimab (livmo), a first-in-class mAb, targets and stabilizes the GARP–TGF-β1 complex, sequestering TGF-β in its inactive form. Livmo is in clinical trials in combination with the anti–PD-1 mAb budigalimab (budi) (NCT03821935, NCT05822752). Methods: Recently, fresh human tumor-derived tissue culture platforms, which retain autologous TME and immune cell content, have emerged as powerful tools to address the gap between clinical data and preclinical models. To better understand the MOA of livmo + budi, we procured fresh tumors from patients (pts) undergoing surgical resection, minced and cultured them for 48h in the presence of livmo ± budi. The functional activity of livmo and budi was determined by assessing tumor cell viability, T-cell effector function, and modulation of immune-suppressive cells. Results: In tumor explant models from 10 pt samples from various indications (NSCLC: n=2; stomach cancer: n=3; HNSCC: n=2; pancreatic cancer: n=1; bladder cancer: n=1; RCC: n=1), treatment with livmo alone led to reduction of tumor cell viability, increase in T-cell effector function, and decrease in immune-suppressive myeloid cells. This effect was further enhanced in combination with budi. Specifically, within the immune cell components, livmo + budi treatment led to no change in the number of Tregs but a 40% reduction in MDSCs and macrophages, both of which depend on TGF-β1 for sustenance and survival. Furthermore, this decrease corresponded with a 50% increase in secretion of granzyme B/IFNγ antitumor T-cell effector functions. Conclusions: These data demonstrate that livmo induces decrease in tumor cell viability, increased antitumor immune cell activation, and remodeling of the immune-suppressive TME, which is further enhanced in combination with budi. These results support the hypothesis that pts would benefit from therapeutic intervention with livmo + budi. 1. Stockis et al. Mol Biosyst 2017;13:1925-35. 2. Zimmer et al. Front Immunol 2022;13:928450. 3. de Streel et al. Nat Commun 2020;11:4545.