bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pengembangan Sumber Daya Manusia Untuk Peningkatan Kinerja Pendidik
Authors: Maulidiya Nurhasni , Ratnaningsih Sita 
Published: December 2024

Pengembangan SDM (Sumber Daya Manusia) merupakan indikator penting dalam manajemen di dalam organisasi khususnya di lembaga pendidikan. Penelitian ini bertujuan untuk mendeskripsikan dan mengevaluasi pengembangan sumber daya manusia di Pondok Pesantren Modern Ummul Quro Al Islami. Penelitian ini menggunakan metodologi kualitatif dan pengumpulan data melalui wawancara, obersevasi dan dokumen. Dengan menggunakan triangulasi sumber serta memeriksa kebenaran data yang digunakan. Pengembangan SDM sangat dibutuhkan untuk peningkatan efektivitas kinerja pendidik agar tercapainya tujuan yang telah direncanakan oleh lembaga pendidikan di Pondok Pesantren Modern Ummul Quro Al Islami. Model pengembangan SDM yang diterapkan di Pondok Pesantren Modern Ummul Quro Al Islami adalah dengan penerapan model pelatihan yang meliputi pelatihan motivasi, pedagogik, administrasi digital dan pembelajaran digital. Kemudian model manajemen berbakat melalui program beasiswa pendidikan untuk pendidik, serta model pembelajaran berkelanjutan melalui program kelompok Musyawarah Guru Mata Pelajaran (MGMP). Pengembangan tersebut memberikan dampak positif terhadap perkembangan SDM. Faktor pendukung terlaksananya pengembangan SDM adalah dengan tersedianya fasilitas sarana dan prasarana yang memadai, sedangkan faktor penghambat pada proses pengembangan SDM adalah waktu dan kegiatan pendidik yang cukup padat sehingga tenaga pendidik yang memiliki lebih dari satu peran perlu membagi waktu dengan peran lainnya. Selain itu motivasi pendidik masih perlu ditingkatkan. Dengan begitu, evaluasi target dan berkala serta umpan balik selalu dilakukan sebagai salah satu upaya dalam proses peningkatan kinerja pendidik
Adapted recreational and sports programs for children with	disabilities: A decade of experience
Authors: Moberg-Wolff Elizabeth , Kiesling Sarah 
Published: December 2024

Objective: To identify and describe community based adapted sports and recreational programs (SARPs) for children with physically disabilities, documenting program types, benefits, challenges, growth and/or decline, and lessons they have learned over a 10-year period. Methods: In 1996, a total of 277 children's hospitals and freestanding rehabilitation hospitals stating that they provided pediatric rehabilitation services were contacted and asked to provide information regarding adapted recreational and sports programs in their region. Seventy-nine SARPs were identified, contacted, and survyed about programming, benefits and challenges they faced. They were then re-surveyed in 2006 for comparison data. Results: Ten years ago, the average SARP served 25 or fewer clients and was led by a therapeutic recreation specialist with assistance from volunteers. Most programs had been in place for 5 years or more, met weekly for 2–3 hours, and were recreational in orientation. Activities varied, with basketball, aquatics, horseback riding and snow skiing being most common. Fund-raisers and grants supported most programs, and securing funding was their greatest challenge. Participant benefits noted by programs included improved socialization, enhanced physical fitness, increased self esteem, improved therapeutic skills (ADL's, transfers, etc.), enhanced cognition, expanded client independence, improved community relations, and enhanced leisure skills. Ten years later, the majority of SARPs noted similar benefits, and reported an increase in number of participants despite continued challenges with funding and staffing. Leadership and mentorship by those with disabilities was still very low, but community awareness of the abilities of those with disabilities had increased. Conclusions: Adapted sports and recreation programs surveyed in 1996 and again in 2006, report overall that their health is good, and many have retained the same programming, financial support mechanisms, leadership and participant mix over the years. Many have increased athlete participation despite financial challenges being a predominant concern. They report that their staying power is dependent on many factors, including leadership, participant referrals, an ample supply of volunteers, and consistent community and financial support. They feel that their success is important to the physical and psychological well-being of individuals with disabilities and that an increased focus on corporate sponsorship, participation and mentorship by those with disabilities may assist with future growth. Increased school involvement, development of more competitive vs. recreational programs, and improved research documenting the physical and psychological benefits of adapted sports programs were also recommended to improve future SARP stability.
Intensity, perception, and descriptive characteristics of chronic	pain in children with cerebral palsy
Authors: Houlihan Christine M. , Hanson Amber , Quinlan Nicole , Puryear Carol , Stevenson Richard D. 
Published: December 2024

Objectives: Children with cerebral palsy (CP) experience bodily pain, leading to functional impairment and decreased quality of life. The purpose of this study is to characterize subjective descriptors of chronic pain in children with CP. Methods: One hundred fifty-seven children were invited to participate in a quantitative pilot survey. Parents were mailed the Varni-Thompson Pediatric Pain Questionnaire, designed to assess three dimensions of pain: sensory (physical aspects), affective (emotional response), and evaluative (the combined intensity of the emotional and physical responses). Parents assessed their child's pain using non-verbal and verbal cues. Results: Fifty-two families responded (33% return rate). Thirty-eight children ages 6–8 years with CP and Gross Motor Function Classification System (GMFCS) levels I–V were included. Ninety percent of families reported that their child was experiencing some pain at the time of the survey. At the time of assessment the children's pain was mild. Their pain, at its worst, was in the distressing range. The two largest GMFCS groups of children, levels I and IV, were compared in both severity and intensity of pain experienced. Increasing intensity of pain was reported in children in the level IV group compared to children classified as level I. Pain severity in all dimensions was reported as increasing in Level IV children compared to Level I. Discussion: Children with CP experience frequent pain, which increases with worsening impairment. Descriptive qualifiers of pain help to elucidate the etiology of various types of pain which would lead to the development of more effective approaches to pain management and treatment.
НАПРЯМИ ВДОСКОНАЛЕННЯ КРИТЕРІЇВ, ЯКІ НЕОБХІДНО ВРАХОВУВАТИ ПРИ ВИЗНАЧЕННІ РОЗМІРУ ВІДШКОДУВАННЯ МАТЕРІАЛЬНОЇ ТА МОРАЛЬНОЇ ШКОДИ
Authors: Мельник В. В. 
Published: December 2024

Актуальність статті полягає в тому, що одним із можливих напрямків удосконалення цього законодавства є уточнення критерії і факторів, які мають враховуватися під час визначенні розміру відшкодування матеріальної та моральної шкоди. Критерії, які необхідно враховувати при визначенні розміру відшкодування матеріальної та моральної шкоди, являють собою набір певних показників, (ознак, факторів, умов тощо), наявність (або відсутність) яких забезпечують вірну оцінку ситуації та правильне визначення характеру й обсягів шкідливих наслідків, прийняття законного та справедливого рішення про зобов’язання сторони (сторін) трудових відносин щодо відшкодування завданої шкоди. Зауважимо, що ми не даремно вказуємо саме на те, що рішення має бути і законним, і справедливим, адже формально законне рішення не завжди є справедливим за своєю суттю, тобто воно може і не відповідати у повній мірі об’єктивно існуючим обставинам ситуації, що виникала. У статті обґрунтовується важливість та необхідність вдосконалення критеріїв, які необхідно враховувати при визначенні розміру відшкодування матеріальної та моральної шкоди. Аргументовано, що відсутність чітких законодавчих положень з приводу критеріїв визначення розмірів шкоди у сфері трудових відносин, не сприяє зміцненню гарантій прав і законних інтересів сторін цих відносин, а також ускладнює належну реалізацію правозахисної та правовідновлюючої функції інституту відшкодування шкоди. Визначено, що в якості необхідних критеріїв визначення розміру морального відшкодування слід виокремлювати: вчинення роботодавцем протиправних дій чи бездіяльності. Тобто не можуть бути підставою для відшкодування шкоди законні дії роботодавця, навіть якщо вони у тій чи іншій мірі негативним чином позначилися на моральній сфері життя людини; наявність реальних негативних наслідків протизаконних дій роботодавця, які за своїм характером можуть викликати, спричинити моральні страждання найманого працівника. Йдеться про те, що моральні страждання, як правило, не виникають самі по собі, вони є наслідком певних суттєвих втрат, фізичних страждань, утисків, дискримінації тощо. Відповідно навряд чи можна вести мову про відшкодування моральної шкоди, якщо порушення має незначний характер і в цілому не може якимось чином позначити на моральному стані найманого працівника за умови, що він перебуваю у нормальному психологічному стані; наявність причинного зв’язку між діями (бездіяльністю) роботодавця та моральними стражданнями найманого працівника.
Exploring Nietzsche's Politics of Isolation from an Epi-eugenic Framework: A New Perspective on the Marriage of Dionysus and Ariadne as “Ariadne AI”
Authors: Steinbuch Thomas 
Published: December 2024

Following the texts of Ecce Homo, the case can be made that Nietzsche was retelling the myth of the Marriage of Dionysus and Ariadne as a story of brother/sister incest in a co-regency, bringing it into line with the divine descent of Pharaonic rulers of Egypt, as reflected in the myth of Isis and Osiris. Nietzsche would seem to be creating a new myth that combines elements we see in the iconography of the Marriage of Dionysus and Ariadne and in the Triumph of Dionysus in which Ariadne is present, but not necessarily as sharing in his triumph, and that he has left behind what is depicted in the iconography to make a philosophical presentation. Ariadne is co-regent with Dionysus in an image of the triumphant development of Dionysian will to power against its denial by an opposing psychology of vengefulness. The psychology of vengefulness seeks to destabilize self awareness in others of the will to power as a self-strengthening force at work in our lives, and does so because of the exactions we must endure in self-overcoming. Following the narrative of Wise § 3/final, her role as Cosima/Ariadne is one of sheltering. Ariadne's triumph, alongside Dionysus, over the reductive psychology of vengefulness against him, represents a victory in what Nietzsche refers to as his “Great Politics.” In this way, Ariadne plays a crucial role in Nietzsche's philosophical project, serving as a protector and guide for those who seek to fully realize the development of will to power in themselves and engage in the ongoing process of self-overcoming. Today, we can partially realize Nietzsche’s thought by using an AI in the role of Ariadne to isolate the pre-established disharmonia as per Nietzsche’s politics of isolation as a sheltering tactic. This use of AI in cultural selection is not to be confused with the previous linkages of Nietzsche’s philosophy to biological eugenics in the early 20th century, with their concerning racist and ablest ideologies.
Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for the treatment of rheumarthritis
Authors: Wang Xiaodong , Mao Jingxin 
Published: December 2024

Objective: β-Sitosterol, which is derived from Vladimiriae Radix (VR), is used for the treatment of rheumatoid arthritis (RA), but the pharmacological mechanisms through which β-sitosterol affects RA have not been fully elucidated.Methods: Through the Traditional Chinese Medicine Systems Pharmacology and Analysis (TCMSP), PubChem, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases, “β-sitosterol-RA”-related genes were obtained, and a target protein interaction network (protein–protein interaction [PPI]) was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the intersecting genes. Discovery Studio 2019 software was used to perform molecular docking on MMP9, CASP3, HSP90AA1, SRC, EGFR, and ALB genes. β-Sitosterol was co-cultured with MH7A cells in three experimental groups: control group (DMSO), positive drug group (methotrexate, 80 μmol/L), and drug intervention group (10, 20, 40, 80, and 160 μmol/L β-sitosterol). The CCK8 method was used to investigate the inhibitory effect of β-sitosterol on the proliferation of MH7A cells. RT-PCR was used to analyze the mRNA expression of the abovementioned core targets.Results: A total of 41 genes associated with β-sitosterol and RA were obtained, mainly involving the FoxO signaling pathway and PI3K/AKT signaling pathway. The molecular docking results suggested that β-sitosterol could bind effectively to six core targets. The experimental results showed that β-sitosterol could significantly inhibit the excessive proliferation of MH7A cells (p&lt; 0.05). The RT-PCR results showed that the expression of MMP9, HSP90AA1, SRC, EGFR, and ALB core genes in the control group was significantly upregulated, while the CASP3 gene was downregulated. Compared to the control group, the mRNA expression of MMP9, HSP90AA1, SRC, EGFR, and ALB decreased (p&lt; 0.01), while the apoptosis-related gene CASP3 increased in both the drug intervention (80 μmol/L β-sitosterol) and positive drug groups (80 μmol/L methotrexate).Conclusion: Hence, β-sitosterol could contribute to the inhibition of RA by modulating cell proliferation and regulating the aforementioned six core proteins, potentially through the regulation of the FoxO and PI3K/AKT signaling pathways.
Heterogeneous immune landscapes and macrophage dynamics in primary and lung metastatic adenoid cystic carcinoma of the head and neck
Authors: Wang Xuelian , Ma Tingyao , Liu Hongfei , Zhang Shujing , Yang Guoliang , Zhao Yue , Kong Lu , Gao Ran , Chen Xiaohong 
Published: December 2024

IntroductionRecurrent or metastatic adenoid cystic carcinoma (ACC) of the head and neck is rare and highly aggressive. Due to the ineffectiveness of immune checkpoint therapies, this study aims to investigate the tumor immune microenvironment of primary tumor tissues and lung metastatic tissues and to comprehend the challenges of immunotherapy.MethodsWe analyzed RNA sequencing data and constructed immune landscapes from 25 primary tumors and 34 lung metastases. The data were then validated by immunohistochemistry and single-cell sequencing analysis.ResultsCompared to adjacent normal tissues, both primary and lung metastatic ACC showed low immune infiltration. Lung metastases had higher immune infiltration levels and antigen presentation scores but also higher T cell exclusion and dysfunction scores. Single-cell sequencing data and immunohistochemistry revealed abundant immunosuppressive tumor-associated macrophages in lung metastases. Patients with high M2 macrophage infiltration had shorter lung metastasis-free survival. DiscussionPrimary and lung metastatic ACC exhibit heterogeneous tumor immune microenvironments. Higher immune cell infiltration in lung metastases is countered by the presence of suppressive tumor-associated macrophages, which may limit effective anti-tumor responses.
SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy
Authors: Cini John K. , Kenney Richard T. , Dexter Susan , McAndrew Stephen J. , Eraslan Rukiye-Nazan , Brody Rich , Rezac Darrel J. , Boohaker Rebecca , Lapi Suzanne E. , Mohan Pankaj 
Published: December 2024

BackgroundCytokines have been promising cancer immunotherapeutics for decades, yet only two are licensed to date. Interleukin-12 (IL-12) is a potent regulator of cell-mediated immunity that activates NK cells and interferon-γ (IFNγ) production. It plays a central role in multiple pathways that can enhance cancer cell death and modify the tumor microenvironment (TME). Attempts to dose rIL-12 were initially successful but IFNγ toxicity in Phase 2 complicated further development in the late 1990s. Since then, better dosing strategies have been developed, but none have achieved the level of cancer control seen in preclinical models. We set out to develop a novel strategy to deliver fully functional IL-12 and other biologics to the TME by binding albumin, taking advantage of its ability to be concentrated and retained in the tumor.MethodsSingle-chain variable fragments (scFv) were identified from a human phage display library that bound human, mouse, and cynomolgus macaque serum albumin, both at physiologic and acidic conditions. These were taken through a series of steps to identify strongly binding molecules that don’t interfere with the normal physiology of albumin to bind FcRn, giving it prolonged half-life in serum, along with SPARC/GP60, which allows albumin to target the TME. A final molecule was chosen and a single mutation was made that minimizes the potential for immunogenicity. This fully human albumin-binding (FHAB®) domain was characterized and manufacturing processes were developed to bring the first drug candidate into the clinic.ResultsOnce identified, the murine form of mIL12-FHAB was studied preclinically to understand its mechanism of action and biodistribution. It was found to be much more efficient at blocking tumor growth compared to murine IL-12, while stimulating significant IFNγ production with minimal toxicity. SON-1010, which uses the human IL-12 sequence, passed through all of the characterization and required toxicology and is currently being studied in the clinic.ConclusionsWe identified and developed a platform technology with prolonged half-life that can target IL-12 and other immune modulators to the TME. Safety and efficacy are being studied using SON-1010 as monotherapy and in combination with checkpoint blockade strategies.
Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy
Authors: Cuiffo Benjamin , Maxwell Melissa , Yan Dingxue , Guemiri Ramdane , Boone Andrew , Bellet Deborah , Rivest Brianna , Cardia James , Robert Caroline , Fricker Simon P. 
Published: December 2024

ObjectiveImmunotherapeutic inhibition of PD-1 by systemically administered monoclonal antibodies is widely used in cancer treatment, but it may cause severe immune-related adverse events (irSAEs). Neoadjuvant PD-1 inhibition before surgery has shown promise in reducing recurrence by stimulating durable antitumor immunity. Local intratumoral (IT) immunotherapy is a potential strategy to minimize irSAEs, but antibodies have limited tumor penetration, making them less suitable for this approach. Therapeutic self-delivering RNAi (INTASYL) is an emerging modality well-suited for neoadjuvant immunotherapy. This study presents preclinical proof-of-concept for PH-762, an INTASYL designed to silence PD-1, currently in clinical development for advanced cutaneous malignancies (ClinicalTrials.gov#NCT06014086).Methods and analysisPH-762 pharmacology was characterized in vitro, and in vivo antitumor efficacy was evaluated using a murine analogue (mPH-762) in syngeneic tumor models with varying PD-1 responsiveness. Bilateral Hepa1-6 models assessed abscopal effects of local treatment. Ex vivo analyses explored mechanisms of direct and abscopal efficacy.ResultsPH-762 was rapidly internalized by human T cells, silencing PD-1 mRNA and decreasing PD-1 surface protein, enhancing TCR-stimulated IFN-γ and CXCL10 secretion. In vivo, IT mPH-762 provided robust antitumor efficacy, local and lymphatic biodistribution, and was well tolerated. Ex vivo analyses revealed that IT mPH-762 depleted PD-1 protein, promoted leukocyte and T cell infiltration, and correlated with tumor control. IT mPH-762 also demonstrated efficacy against untreated distal tumors (abscopal effect) by priming systemic antitumor immunity.ConclusionThese data support PH-762 as a promising candidate for neoadjuvant immunotherapy in clinical studies.
The effect of Torreya grandis inter-cropping with Polygonatum sibiricum on soil microbial community
Authors: Wang Quanchao , Peng Xiaojie , Yuan Yuxuan , Zhou Xudong , Huang Jianqin , Wang Haonan 
Published: December 2024

BackgroundInter-cropping is a reasonable planting pattern between different plants. Inter-cropping of Torreya grandis with Polygonatum sibiricum is a relatively mature planting pattern in China, which has been applied to improve soil ecological environment and reduce the occurrence of pests and diseases in China. However, there is currently limited knowledge on the response of soil microbial communities to this practice.MethodsIn this study, we employed Illumina MiSeq sequencing coupled with Functional Annotation of Prokaryotic Taxa (FAPROTAX) and Fungi Functional Guild (FUNGuild) analyses to investigate the dynamic changes in soil microbial communities across seven treated groups [the bulk soil of the T. grandis inter-cropping with P. sibiricum (IB), the bulk soil for mono-cropping of P. sibiricum (PB), the bulk soil for mono-cropping of T. grandis (TB), the P. grandis rhizosphere soil of the T. grandis inter-cropping with P. sibiricum (IPR), the rhizosphere soil for mono-cropping of P. sibiricum (PR), the T. grandis rhizosphere soil of the T. grandis inter-cropping with P. sibiricum (ITR), and the rhizosphere soil for mono-cropping of T. grandis (TR)].ResultsThe results showed that the rhizosphere soil of Torreya-Polygonatum inter-cropping exhibited higher microbial community richness, diversity and evenness than mono-cropping (ITR &gt; TR, IPR &gt; PR). Inter-cropping increased the abundance of Micrococcaceae, Xanthobacteraceae, Saitozyma, while decreased Bacillus, Burkholderia, Streptomyces, Cladosporium, and Gibberella significantly of the rhizosphere soil of T. grandis. Further, the abundance of pathogens, such as Fusarium and Neocosmospora, was higher in mono-cropping samples compared to inter-cropping. There existed distinct variations in bacterial and fungal communities among all groups except for IB and TB. The FAPROTAX and FUNGuild analyses results indicated that inter-cropping significantly enhanced soil microbial function associated with nutrient cycling and exhibited a consistent increase in the relative abundance of nitrogen-cycling and carbon-cycling bacteria, and decreased the abundance of plant pathogen guild in the inter-cropping sample ITR compared to the mono-cropping TR.ConclusionOur findings suggest that T. grandis inter-cropping with P. sibiricum not only enhance the diversity of soil microbial communities, but also improve the nitrogen and carbon cycling functions. In addition, the inter-cropping can effectively reduce the relative abundance of some soil-borne pathogens for T. grandis and P. sibiricum, indicating that this intercropping method may alleviate the impact of pathogens on crops, thus providing assistance for plant disease prevention and sustainable management.