bluuebunny/crossref_metadata_2025 huggingface dataset:
PKMS “SADAR WISATA DAN SAPTA PESONA PADA MASYARAKAT DESA PANTAI INDUK GERUNG LOMBOK BARAT“
Authors: Sri Susanty  , Ander Sriwi  , Murianto Murianto , Lalu Mahsar
Published: August 2024

Community service programs on the promotion of Tourism Consciousness and ‘Sapta Pesona’ to the Pantai Induk Gerung West Lombok need to be carried out based on preliminary observations of the Mataram Tourism College community service team. Previously, this beach was a favorite tourist spot which was always busy with many tourists because it has a beach with beautiful natural views. but now, the beach is very quiet because of high coastal erosion and a dirty environment. Pokdarwis find it difficult to disseminate information to the public about tourism awareness programs and implement sapta pesona. The program is implemented using a lecture and discussion approach and problem mapping. This event, which was attended by 25 participants, looked enthusiastic during the counseling and problem mapping.  This socialization program is very important for Pokdarwis and the local community as a basis for understanding tourism, so that it can foster high motivation and participation in tourism development at Pantai Induk.
DINAMIKA PENGELOLAAN SARHUNTA OLEH MASYARAKAT DI KAWASAN EKONOMI KHUSUS MANDALIKA LOMBOK TENGAH-INDONESIA
Authors: Rizal Kurniansah  , Masrun  , Jumhur Hakim
Published: August 2024

Tujuan dari penelitian ini adalah untuk menganalisis keterampilan masyarakat dalam mengelola sarhunta di KEK Mandalika sebelum dan sesudah sarhunta dikembangkan. Kedua, untuk menganalisis dampak sosial dan ekonomi yang diperoleh sebelum dan sesudah sarhunta dikembangkan. Metode pengumpulan data yang digunakan dalam penelitian ini adalah observasi, wawancara, studi literatur dan dokumentasi. Analisis data yang digunakan adalah deskriptif kualitatif. Berdasarkan hasil penelitian yang telah dilakukan, keterampilan masyarakat sebelum mendapatkan bantuan program sarhunta dari pemerintah, masyarakat tidak memiliki keterampilan sama sekali dalam mengelola tempat tinggal (sarhunta). Namun setelah mendapatkan bantuan, masyarakat memiliki keterampilan tersebut karena telah mendapatkan beberapa pelatihan dari stakeholder terkait. Meskipun begitu, keterampilan yang dimiliki masyarakat sebenarnya belum maksimal, karena mereka belum mampu mengelola sarhunta mereka sesuai dengan standar penginapan pada umumnya. Selain itu, masyarakat masih kesulitan dalam memasarkan sarhunta mereka karena minimnya pengetahuan tentang pemasaran, dan harus bersaing dengan berbagai tempat penginapan lain yang sudah berkembang dengan baik. Sehingga mereka cenderung hanya menunggu tamu yang datang ke tempat mereka masing-masing. Selanjutnya, dampak sosial dan ekonomi yang didapatkan oleh masyarakat sebelum dan sesudah sarhunta dibangun antara lain meningkatnya pendapatan masyarakat, terciptanya lapangan pekerjaan bagi anggota keluarga, ekosistem ekonomi lokal di sekitar sarhunta terus berkembang, budaya lokal semakin dikenal oleh wisatawan, adanya pengembangan dan pelatihan keterampilan, meningkatnya integrasi sosial antara wisatawan dan masyarakat lokal.
PENGARUH RELATIONSHIP MARKETING TERHADAP LOYALITAS PENGGUNA JASA KURSUS ONLINE “Studi tentang Loyalitas Pengguna Kursus Online pada Nuraz Institute, Tarakan”
Authors: Deni Marsha
Published: August 2024

The purpose of this study is to analyze and determine the effect of relationship marketing on user loyalty for online course at the Nuraz Institute, Tarakan. The method used in this research is quantitative with an explanatory approach. The population in the study included all users of the online course at the Nuraz Institute with a saturated sample of 33 respondents. The data analysis technique used is the regression analysis which aims to determine the effect of the relationship marketing variable toward the user loyalty. The results showed that there was an influence of relationship marketing towards user loyalty for online course at the Nuraz Institute.  The relatioship marketing has a very strong influence towards customer loyalty. Marketing and user loyalty in the business world play an important role to running a business, especially in the service provider business.
BUDAYA MEGEDONG-GEDONGAN SEBAGAI IMPLEMENTASI ETNOPEDAGOGI PADA BIMBINGAN KLINIK KEBIDANAN DALAM SUBSTANSI STIMULASI TUMBUH KEMBANG ANAK MATA KULIAH KEBIDANAN KOMUNITAS DI TPMB NI KETUT NURIASIH TAHUN 2023
Authors: Sinta Javani  , I Wayan Suastra  , Ida Bagus Putu Arnyana
Published: August 2024

Pembelajaran berbasis budaya lokal dapat dijelaskan sebagai budaya yang diintegrasikan  sebagai  alat  bagi  proses  belajar  untuk memotivasi  siswa  dalam  mengaplikasikan  pengetahuan. Studi ini memberikan gambaran upaya etnopedagogi dalam bimbingan klinik kebidanan dalam substansi stumulasi tumbuh kembang anak mata kuliah kebidanan komunitas di TPMB Ni Ketut Nuriasih Tahun 2023. Pendekatan penelitianini adalah metode kualitatif, denganjenis fenomenologi. Menurut Sugiyono (2021), data penelitian kualitatif adalah data yang berbentuk kata, kalimat, narasi, gerak tubuh,ekspresi wajah, bagan, gambar dan foto. Data ini dapat terbagi menjadi dua macam yakni data kualitatif empiris dan data kualitatif bermakna. Dalam penelitian ini, adalah data kualitatif bermakna, sebab peneliti mengambarkan esensi dibalik eksistensi, data dibalik fakta yang tampak. Dengan mengambil bentuk naratif-deskriptif. Teknik pengumpulan data adalah dengan observasi, wawancara dan dokumentasi. Adapun lokasi penelitian adalah di TPMB Ni Ketut Nuriasih. Hasil penelitian ini adalah etnopedagogi secara  konsep terus berkembang dan secara praktisnya mulai nyaman diterapkan diberbagai tanan pendidikan termasuk pada tanan pembingan klinik maupun kebidanan komunitas. Tujuan etnopedagogi sebagai pembelajaran yang menyenangkan serta definisi etnopedagogi yakni pendidikan dari masyarakat, untuk masyarakat,dan oleh masyarakat diimplemtasi sebagai lesson learnt guna melakukan pendekatan dalam mengedukasi dan mendampingi pasien pada pendekatan pembelajaran kebidanan kemunitas yang erat dengan keberadaan profsi bidan di tengah-tengah masyarakat. Kontribusi positif, dirasakan oleh preceptor atau mentor dalam memberikan bimbingan dan begitu juga oleh peserta didik dalam konteks  hasil belajar maupun pendidikan karakter peserta didik yang bermuara pada pentingnya kedudukan kearifan lokal dalam asuhan kebidanan sebagai pendekatan untuk mengkomunikasikan asuhan kebidana di komunitas yang berbasis bukti namun tetap menempatkan klien atau masyarakat sebagi subyek bukan obyek pelayanan kebidanan
ANALISIS STRATEGI DALAM PENGIMPLEMENTASIAN ECOTOURISM DI DESA WISATA HIJAU BILEBANTE, LOMBOK TENGAH, NTB, DI TENGAH ERA PEMBANGUNAN BERKELANJUTAN
Authors: Lalu Puttrawandi Karjaya  , Rizky Akbar Danuarta  , Nona Namira Najwa  , Silvia Dwi Hartina  , Vidrian Azandra Xeriscky
Published: August 2024

This journal discusses ecotourism applied in Bilebante village as a form of tourism that emphasizes nature conservation and environmental sustainability. This journal aims to analyze strategies in implementing ecotourism in the green tourism village of Bilebante, Central Lombok, NTB. The method that will be used in writing this journal is qualitative research by collecting secondary data and observation through the interview process. In this context, Bilebante Village in Central Lombok, NTB, applies the concept of ecotourism to green tourism as a sustainable development effort. This itself will certainly have a domino effect on several dimensions in the economic space with a wider range, the development of ecotourism makes the local community have many options in using the benefits of tourism as employment. This research will use the concepts of ecotourism and sustainable tourism to analyze the implementation in Bilebante Village, with a focus on nature conservation, community participation, and the environment. In the end, this research is expected to conclude on how the strategy of implementing ecotourism in Bilebante Village without feeling that sustainable development is a threat to the concept of tourism applied in the village, and can provide insight to readers related to ecotourism, especially in the green tourism village of Bilebante, Lombok, NTB.
Fakir Miskin dan Anak Telantar dalam Dekapan Panti Asuhan Muhammadiyah Padang Laweh Malalo Kabupaten Tanah Datar Tahun 2010-2021
Authors: Radiatul Adawiyah Radiatul Adawiyah , Zaiyardam Zaiyardam
Published: August 2024

This research examines "The Poor and Abandoned Children in the Arms of the Padang Laweh Malalo Muhammadiyah Orphanage, Tanah Datar Regency, 2010-2021". The four main actors in this research are foster children, guardians (mamak), the state, and Muhammadiyah. By understanding the relationship dynamics between these four actors, who will play a role in caring for abandoned and poor children? Is it the state, guardians, or Muhammadiyah? This research uses a multidimensional approach. This method strategy is necessary for analyzing research topics thoroughly. The method uses historical methods: heuristics, criticism, interpretation, and historiography. The results of the research show that the Muhammadiyah Padang Laweh Malalo Orphanage plays a role in accommodating the poor and neglected children, especially amid delays or neglect of guardians, as well as the state's indifference, a meaningful initiative and served as a refuge for abandoned children. The study concludes that guardians and the state no longer carry out their roles and functions so that children enter orphanages. The state, by Article 34 Paragraph 1 of the Law, which declares "The Poor and Abandoned Children are cared for by the State," has proven unable to carry out its role effectively in providing protection and care for marginalized children. Muhammadiyah is a social or religious organization that has proven to be a savior for marginalized groups.
КТО ИЗОБРАЖЕН НА КАРТИНЕ Н. П. БОГДАНОВА-БЕЛЬСКОГО «БУДУЩИЙ ИНОК»?
Authors: Фетисенко Ольга Леонидовна
Published: August 2024

На основе архивных материалов, впервые опубликованных автором статьи в 2024 г. (переписка С. А. Рачинского с И. Л. Леонтьевым и сопутствующие документы), устанавливается, кто позировал живописцу Н. П. Богданову-Бельскому (1868–1945) для его известной картины «Будущий инок» (1889) и для иконы «Спаситель, идущий по водам» (1893). «Моделью» послужил ученик и «келейник» С. А. Рачинского Семен Дорофеевич Васильев, ранее не привлекавший внимания многочисленных исследователей истории Татевской школы. Цитируются обнаруженные в Рукописном отделе Пушкинского Дома письма «будущего инока».
Preparation of a scientific edition of the correspondence between S. A. Rachinsky and I. L. Leontiev (1891– 1900) made it possible to find out many previously unknown details concerning the close circle of the famous teacher. In particular, it was possible to establish who served as the model for the young man depicted in Bogdanov-Belsky's painting «The Future Monk» (1889). This was Rachinsky's disciple and «cell attendant» Semyon Vasiliev, who had not previously attracted the attention of numerous researchers of the history of the Tatev school. The article quotes his letters discovered in the Manuscript Department of the Pushkin House.
Role of post-translational modifications of Sp1 in cardiovascular diseases
Authors: Sun Xutao , Zhou Qi , Xiao Chengpu , Mao Caiyun , Liu Ying , Chen Guozhen , Song Yunjia
Published: August 2024

Specific protein 1 (Sp1) is pivotal in sustaining baseline transcription as well as modulating cell signaling pathways and transcription factors activity. Through interactions with various proteins, especially transcription factors, Sp1 controls the expression of target genes, influencing numerous biological processes. Numerous studies have confirmed Sp1’s significant regulatory role in the pathogenesis of cardiovascular disorders. Post-translational modifications (PTMs) of Sp1, such as phosphorylation, ubiquitination, acetylation, glycosylation, SUMOylation, and S-sulfhydration, can enhance or modify its transcriptional activity and DNA-binding stability. These modifications also regulate Sp1 expression across different cell types. Sp1 is crucial in regulating non-coding gene expression and the activity of proteins in response to pathophysiological stimuli. Understanding Sp1 PTMs advances our knowledge of cell signaling pathways in controlling Sp1 stability during cardiovascular disease onset and progression. It also aids in identifying novel pharmaceutical targets and biomarkers essential for preventing and managing cardiovascular diseases.
Exploring the etiology of dilated cardiomyopathy using Mendelian randomization
Authors: Xue SiYang , Jiang HongJu
Published: August 2024

Background

Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach.

Objective

To investigate the etiology of DCM through Mendelian randomization analysis.

Methods

Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods.

Results

The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744–0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010–1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085–1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference.

Conclusion

Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.
Smartphone addiction habit is positively associated with coronary artery disease and its severity in Chinese adults: a case-control study
Authors: Zhu Jun , Wang Sibo , Wu Yujie , Gu Lingfeng , Ma Yao , Wang Yaxin , Wang Liansheng
Published: August 2024

Background

Coronary artery disease (CAD) has a high incidence and poor prognosis worldwide. It has been confirmed that smartphone addiction (SA) habit can increase the incidence of hypertension and obesity in adolescents. However, the association of SA with CAD and its severity in Chinese adults remains largely unknown.

Methods

A total of 700 Chinese adults (aged 18–70 years) including 350 CAD patients and 350 control subjects were enrolled. The Smartphone Addiction Scale Short Version (SAS-SV) was used to measure SA habit, and the Pittsburgh sleep quality index (PSQI) was used to assess sleep quality. Multiple logistic regression was employed to analyze the relationship between SA habit and CAD.

Results

After adjusting for age, smoking, hypertension, type 2 diabetes mellitus, and other risk factors, there was a significant association between SA habit and CAD in adults (p < 0.001). Subgroup analysis showed that there were statistical differences in the correlation between SA habit and CAD in the hypertension, ≤55 years age old, and female subgroups. Moreover, we performed a subgroup analysis based on the number of coronary artery lesions. The result showed that the rate of SA habit in the three-vessel disease group was the highest (p < 0.001). We applied Gensini score to evaluate the severity of coronary artery lesions (median Gensini score, 34) and divided all CAD patients into high Gensini score group (>34) and low Gensini score group (≤34), respectively. Compared with low Gensini score group, patients in high Gensini score group were more likely to have SA habit (p = 0.049).

Conclusions

There is a positive association of SA habit with CAD and its severity in Chinese adults.
Case Report: Lethal mitochondrial cardiomyopathy linked to a compound heterozygous variant of PARS2
Authors: Jing Siyuan , Yao Qiuyan , Wu Mei , Li Yifei
Published: August 2024

Introduction

Variants in the PARS2 gene have been previously associated with developmental and epileptic encephalopathy. PARS2 deficiency was characterized as a neurodevelopmental and neurodegenerative disorder with early-onset seizures and global developmental delay. Herein, we reported the first case with severe heart failure due to lethal mitochondrial cardiomyopathy with PARS2 compound heterozygous variants.

Case presentation

This patient demonstrated fatigue, chest tightness, and shortness of breath. An acute major illness had been identified at the initial evaluation, which was characterized by severe diaphoresis, dizziness, and fatigue. Blood–urine tandem mass spectrometry found multiple disorders in acid metabolism, characterized as increased homovanillic acid (130.39 mmol/L) and 2-hydroxyisovaleric acid (1.70 mmol/L), which are associated with myocardial injuries. Therefore, an inherited metabolic disorder was suspected and whole-exome sequencing was performed, revealing a novel compound heterozygous variant of c.953C>T and c.283G>A on PARS2. Echocardiography confirmed the findings from the MRI, which presented an increased left ventricular diameter at the end of the diastolic stage. The molecular structure of SYPM was established as AF-Q7L3T8-F1, and the identified mutant sites were located in the proline-tRNA ligase domain. However, the patient died due to severe heart failure.

Conclusion

This is the first case to reveal a novel compound heterozygous variant of PARS2-induced lethal cardiomyopathy with unreversed heart failure. Thus, this report enhances our understanding of mitochondrial tRNA function in maintaining heart function.
Case Report: Extraction of a stylet-driven lead for left bundle branch area pacing >2 years after implantation
Authors: Romic Ivana Grgic , Bastiancic Ana Lanca , Zidan David , Mavric Mate , Brusich Sandro
Published: August 2024

Left bundle branch pacing has recently emerged as a significant alternative to right ventricular pacing. The rate of implanted stylet-driven septal leads is expected to increase substantially in the coming years, along with the need to manage long-term complications. Experience in extracting these leads is currently very limited; however, the number of complex extractions is anticipated to increase in the future. We report a complex case involving the extraction of a long-dwelling Solia lead used for left bundle branch pacing in a 21-year-old man. The lead was extracted through the implant vein 27 months after implantation, using a methodology that involved a locking stylet and compression coil. The new lead insertion was challenging due to venous occlusion but after successful venoplasty, the His lead was successfully implanted. The postoperative course was uneventful, demonstrating the feasibility of extraction without complications.
Acceptability of digital health technologies in early Parkinson's disease: lessons from WATCH-PD
Authors: Kangarloo T. , Latzman R. D. , Adams J. L. , Dorsey R. , Kostrzebski M. , Severson J. , Anderson D. , Horak F. , Stephenson D. , Cosman J.
Published: August 2024

Introduction

Digital health technologies (DHTs) have the potential to alleviate challenges experienced in clinical trials through more objective, naturalistic, and frequent assessments of functioning. However, implementation of DHTs come with their own challenges, including acceptability and ease of use for study participants. In addition to acceptability, it is also important to understand device proficiency in the general population and within patient populations who may be asked to use DHTs for extended periods of time. We thus aimed to provide an overview of participant feedback on acceptability of DHTs, including body-worn sensors used in the clinic and a mobile application used at-home, used throughout the duration of the Wearable Assessments in the Clinic and at Home in Parkinson's Disease (WATCH-PD) study, an observational, longitudinal study looking at disease progression in early Parkinson's Disease (PD).

Methods

82 participants with PD and 50 control participants were enrolled at 17 sites throughout the United States and followed for 12 months. We assessed participants' general device proficiency at baseline, using the Mobile Device Proficiency Questionnaire (MDPQ). The mean MDPQ score at Baseline did not significantly differ between PD patients and healthy controls (20.6 [2.91] vs 21.5 [2.94], p = .10).

Results

Questionnaire results demonstrated that participants had generally positive views on the comfort and use of the digital technologies throughout the duration of the study, regardless of group.

Discussion

This is the first study to evaluate patient feedback and impressions of using technology in a longitudinal observational study in early Parkinson's Disease. Results demonstrate device proficiency and acceptability of various DHTs in people with Parkinson's does not differ from that of neurologically healthy older adults, and, overall, participants had a favorable view of the DHTs deployed in the WATCH-PD study.
Association between metabolic disorders and clinicopathologic features in endometrial cancer
Authors: Wang Yuanpei , Liu Qianwen , Sun Yi , Wu Weijia , Cheng Xiaoran , Chen Xuerou , Ren Fang
Published: August 2024

Background

In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients.

Methods

In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method.

Results

The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC.

Conclusion

Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.
A dynamic surface water extent service for Africa developed through continental-scale collaboration
Authors: Halabisky Meghan , Yuan Fang , Adimou Ghislain , Birchall Eloise , Boamah Edward , Burton Chad , Chong Ee-Faye , Hall Lisa , Jorand Cedric , Leith Alex , Lewis Adam , Mamane Bako , Mar Fatou , Moghaddam Negin , Ongo David , Rebelo Lisa-Maria
Published: August 2024

Spatially explicit, near real time information on surface water dynamics is critical for understanding changes in water resources, and for long-term water security planning. The distribution of surface water across the African continent since 1984 and updated as every new Landsat scene becomes available is presented here, and validated for the continent for the first time. We applied the Water Observations from Space (WOfS) algorithm, developed and well-tested in Australia, to every Landsat scene acquired over Africa since the mid 1980s to provide spatial information on surface water dynamics over the past 30+ years. We assessed the accuracy of WOfS using aerial and satellite imagery. Four regional geospatial organisations, coordinated through the Digital Earth Africa Product Development Task Team, conducted the validation campaign and provided both the regional expertise and experience required for a continental-scale validation effort. We assessed whether the point was wet, dry, or cloud covered, for each of the 12 months in 2018, resulting in 34,800 labelled observations. As waterbodies larger than 100 km2 are easy to identify with Landsat resolution data and can thus boost accuracy, these were masked out. The resulting overall accuracy of the water classification was 82%. WOfS in Africa is expected to be used by ministries and departments of agriculture and water across the continent, by international organisations, academia, and the private sector. A large-scale collaborative effort, which included regional and technical skills spanning two continents was required to create a service that is regionally accurate and is both hosted on, and implemented operationally from, the African continent.
Stakeholder perspectives on factors that influence global prioritization for MNH in humanitarian settings
Authors: Adler Alicia , Kozuki Naoko , Mothupi Mamothena
Published: August 2024

Background

Maternal and newborn mortality rates are disproportionately high in crisis and conflict-affected countries. This study aims to understand factors influencing how MNH in humanitarian and fragile settings (HFS) is prioritized on the global health agenda during the Sustainable Development Goal (SDG) era. This includes examining the policies and processes driving agenda setting and decision-making, as well as the perceptions of global actors. It further reflects on the role of global milestones, reports, convenings, and high-level champions, based on the premise that global prioritization leads to increased attention and resource allocation, ultimately contributing to improved outcomes for mothers and newborns in crisis-affected areas.

Methods

A qualitative study conducted from April 2022 to June 2023, employing a desk review and 23 semi-structured key informant interviews with global actors from donor agencies, implementing organizations, research institutes, United Nations agencies, professional associations, and coalitions, predominantly based in the Global North. Data were analyzed using inductive thematic analysis and the research was guided by the Walt and Gibson Health Policy Triangle framework.

Results

Participants believe that global agenda-setting and investment decisions for MNH are primarily driven by UN agencies, donors, and implementing organizations at the global level. Although the Millennium Development Goal era successfully prioritized MNH, this focus has diminished during the SDGs, especially for HFS. Identified barriers include the complexity of reducing mortality rates in these contexts, limited political will, MNH investment fatigue, and a preference for quick wins. Fragmentation between humanitarian and development sectors and unclear mandates in protracted crises also hinder progress. Without enhanced global advocacy, accountability, and targeted investments in HFS, respondents deem global MNH targets unattainable.

Conclusions

While waning donor interest and the siloing of HFS in global MNH decision-making pose challenges, targeted actions to address these barriers may include designating quotas for humanitarian actors in global MNH convenings, developing shared messages that convey common interests, and adopting an equity lens. Prioritizing MNH in HFS on the global agenda demands sustained commitment to ensure these settings are not an afterthought through dedicated advocacy and accountability, high-level political engagements, global milestones, and by leveraging opportunities to capture mainstream interest. Failing to shift global priorities will result in continued stagnation and worsening MNH outcomes across HFS.
GPCRs overexpression and impaired fMLP-induced functions in neutrophils from chronic kidney disease patients
Authors: Scharf Pablo , Sandri Silvana , Rizzetto Felipe , Xavier Luana Filippi , Grosso Daniela , Correia-Silva Rebeca D. , Farsky Pedro S. , Gil Cristiane D. , Farsky Sandra Helena Poliselli
Published: August 2024

Introduction

G-protein coupled receptors (GPCRs) expressed on neutrophils regulate their mobilization from the bone marrow into the blood, their half-live in the circulation, and their pro- and anti-inflammatory activities during inflammation. Chronic kidney disease (CKD) is associated with systemic inflammatory responses, and neutrophilia is a hallmark of CKD onset and progression. Nonetheless, the role of neutrophils in CKD is currently unclear.

Methods

Blood and renal tissue were collected from non-dialysis CKD (grade 3 - 5) patients to evaluate GPCR neutrophil expressions and functions in CKD development.

Results

CKD patients presented a higher blood neutrophil-to-lymphocyte ratio (NLR), which was inversely correlated with the glomerular filtration rate (eGFR). A higher frequency of neutrophils expressing the senescent GPCR receptor (CXCR4) and activation markers (CD18+CD11b+CD62L+) was detected in CKD patients. Moreover, CKD neutrophils expressed higher amounts of GPCR formyl peptide receptors (FPR) 1 and 2, known as neutrophil pro- and anti-inflammatory receptors, respectively. Cytoskeletal organization, migration, and production of reactive oxygen species (ROS) by CKD neutrophils were impaired in response to the FPR1 agonist (fMLP), despite the higher expression of FPR1. In addition, CKD neutrophils presented enhanced intracellular, but reduced membrane expression of the protein Annexin A1 (AnxA1), and an impaired ability to secrete it into the extracellular compartment. Secreted and phosphorylated AnxA1 is a recognized ligand of FPR2, pivotal in anti-inflammatory and efferocytosis effects. CKD renal tissue presented a low number of neutrophils, which were AnxA1+.

Conclusion

Together, these data highlight that CKD neutrophils overexpress GPCRs, which may contribute to an unbalanced aging process in the circulation, migration into inflamed tissues, and efferocytosis.
Systemic toxicity of CAR-T therapy and potential monitoring indicators for toxicity prevention
Authors: Li Jingxian , Chen Huiguang , Xu Chaoping , Hu Mengci , Li Jiangping , Chang Wei
Published: August 2024

Malignant tumors of the hematologic system have a high degree of malignancy and high mortality rates. Chimeric antigen receptor T cell (CAR-T) therapy has become an important option for patients with relapsed/refractory tumors, showing astonishing therapeutic effects and thus, it has brought new hope to the treatment of malignant tumors of the hematologic system. Despite the significant therapeutic effects of CAR-T, its toxic reactions, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cannot be ignored since they can cause damage to multiple systems, including the cardiovascular system. We summarize biomarkers related to prediction, diagnosis, therapeutic efficacy, and prognosis, further exploring potential monitoring indicators for toxicity prevention. This review aims to summarize the effects of CAR-T therapy on the cardiovascular, hematologic, and nervous systems, as well as potential biomarkers, and to explore potential monitoring indicators for preventing toxicity, thereby providing references for clinical regulation and assessment of therapeutic effects.
Heterogeneity in immune cell composition is associated with Mycobacterium tuberculosis replication at the granuloma level
Authors: Cooper Sarah K. , Ackart David Forrest , Lanni Faye , Henao-Tamayo Marcela , Anderson G. Brooke , Podell Brendan K.
Published: August 2024

The control of bacterial growth is key to the prevention and treatment of tuberculosis (TB). Granulomas represent independent foci of the host immune response that present heterogeneous capacity for control of bacterial growth. At the whole tissue level, B cells and CD4 or CD8 T cells have an established role in immune protection against TB. Immune cells interact within each granuloma response, but the impact of granuloma immune composition on bacterial replication remains unknown. Here we investigate the associations between immune cell composition, including B cell, CD4, and CD8 T cells, and the state of replicating Mycobacterium tuberculosis (Mtb) within the granuloma. A measure of ribosomal RNA synthesis, the RS ratio®, represents a proxy measure of Mtb replication at the whole tissue level. We adapted the RS ratio through use of in situ hybridization, to identify replicating and non-replicating Mtb within each designated granuloma. We applied a regression model to characterize the associations between immune cell populations and the state of Mtb replication within each respective granuloma. In the evaluation of nearly 200 granulomas, we identified heterogeneity in both immune cell composition and proportion of replicating bacteria. We found clear evidence of directional associations between immune cell composition and replicating Mtb. Controlling for vaccination status and endpoint post-infection, granulomas with lower CD4 or higher CD8 cell counts are associated with a higher percent of replicating Mtb. Conversely, changes in B cell proportions were associated with little change in Mtb replication. This study establishes heterogeneity across granulomas, demonstrating that certain immune cell types are differentially associated with control of Mtb replication. These data suggest that evaluation at the granuloma level may be imperative to identifying correlates of immune protection.
Safety and practicality of an excisional lymph node study driving HIV cure research in South Africa
Authors: Khaba Trevor , Papadopoulos Andrea Olga , Nkosi Thandeka , Nxele Sifundo , Ngubane Thandekile , Jajbhay Ismail , Pansegrouw Johan , Ndhlovu Zaza M.
Published: August 2024

Introduction

Studying diseased human tissues offers better insights into the intricate interactions between pathogens and the human host. In conditions such as HIV and cancers, where diseases primarily manifest in tissues, peripheral blood studies are limited in providing a thorough understanding of disease processes and localized immune responses.

Methods

We describe a study designed to obtain excisional lymph nodes from volunteers for HIV reservoir studies. Since study commencement in 2015, 181 lymph node excisions have been performed, resulting in collection of 138 lymph node tissues. Lymph nodes were surgically excised from study volunteers using a minimally invasive procedure, performed in a minor theater under local anesthesia.

Results

The surgery takes less than 30 minutes to complete, minimizing risk and stress on the volunteer. The small incision made during the procedure typically heals within a week. The associated discomfort is generally manageable, and participants are often able to resume their regular activities within a day. Only 5.5% of the study participants experienced minor adverse events, such as swelling and prolonged wound healing, recovering within 2 weeks with no serious adverse events reported.

Discussion

Our study demonstrates that when done with outmost care, obtaining excised lymph nodes for research is relatively safe and practical.
Obesity, dysbiosis and inflammation: interactions that modulate the efficacy of immunotherapy
Authors: Yende Ashutosh S. , Sharma Dipali
Published: August 2024

Recent years have seen an outstanding growth in the understanding of connections between diet-induced obesity, dysbiosis and alterations in the tumor microenvironment. Now we appreciate that gut dysbiosis can exert important effects in distant target tissues via specific microbes and metabolites. Multiple studies have examined how diet-induced obese state is associated with gut dysbiosis and how gut microbes direct various physiological processes that help maintain obese state in a bidirectional crosstalk. Another tightly linked factor is sustained low grade inflammation in tumor microenvironment that is modulated by both obese state and dysbiosis, and influences tumor growth as well as response to immunotherapy. Our review brings together these important aspects and explores their connections. In this review, we discuss how obese state modulates various components of the breast tumor microenvironment and gut microbiota to achieve sustained low-grade inflammation. We explore the crosstalk between different components of tumor microenvironment and microbes, and how they might modulate the response to immunotherapy. Discussing studies from multiple tumor types, we delve to find common microbial characteristics that may positively or negatively influence immunotherapy efficacy in breast cancer and may guide future studies.
Role and mechanisms of mast cells in brain disorders
Authors: Huang Xuanyu , Lan Ziwei , Hu Zhiping
Published: August 2024

Mast cells serve as crucial effector cells within the innate immune system and are predominantly localized in the skin, airways, gastrointestinal tract, urinary and reproductive tracts, as well as in the brain. Under physiological conditions, brain-resident mast cells secrete a diverse array of neuro-regulatory mediators to actively participate in neuroprotection. Meanwhile, as the primary source of molecules causing brain inflammation, mast cells also function as the “first responders” in brain injury. They interact with neuroglial cells and neurons to facilitate the release of numerous inflammatory mediators, proteases, and reactive oxygen species. This process initiates and amplifies immune-inflammatory responses in the brain, thereby contributing to the regulation of neuroinflammation and blood-brain barrier permeability. This article provides a comprehensive overview of the potential mechanisms through which mast cells in the brain may modulate neuroprotection and their pathological implications in various neurological disorders. It is our contention that the inhibition of mast cell activation in brain disorders could represent a novel avenue for therapeutic breakthroughs.
CircRNAs expression profile and potential roles of circRERE-PMN in pre-metastatic lungs
Authors: Shi Huifang , Wang Yan , Chen Lei , Li Yuanyuan , Qin Yan , Lv Jie
Published: August 2024

The successful pulmonary metastasis of malignant cancer cells depends on the survival of circulating tumor cells in a distant and hostile microenvironment. The formation of a pre-metastatic niche (PMN) creates a supportive environment for subsequent metastasis. Circular RNAs (circRNAs) are increasingly acknowledged as crucial elements in the mechanisms of metastasis due to their stable structures and functions, making them promising early metastasis detection markers. However, the specific expression patterns and roles of circRNAs in the lungs before metastasis remain largely unexplored. Our research aims to chart the circRNA expression profile and assess their impact on the lung PMN. We developed a lung PMN model and employed comprehensive RNA sequencing to analyze the differences in circRNA expression between normal and pre-metastatic lungs. We identified 38 significantly different circRNAs, primarily involved in metabolism, apoptosis, and inflammation pathways. We then focused on one specific circRNA, circ:chr4:150406196 – 150406664 (circRERE-PMN), which exhibited a significant change in expression and was prevalent in myeloid-derived suppressor cells (MDSCs), alveolar epithelial cells, and macrophages within the pre-metastatic lung environment. CircRERE-PMN was found to potentially regulate apoptosis and the expression of cytokines and chemokines through its interaction with the downstream target HUR in alveolar epithelial cells. Overall, our study highlights the crucial role of circRNAs in the formation of lung PMNs, supporting their potential as diagnostic or therapeutic targets for lung metastasis.
Potential of gamma/delta T cells for solid tumor immunotherapy
Authors: Zhu Dantong , Ren Xijing , Xie Wanting , Chen Jianjun , Liang Shiying , Jiang Mingzhe , Wang Junyi , Zheng Zhendong
Published: August 2024

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy.
RNA modifications in insects
Authors: Jiao Yaoyu , Palli Subba Reddy
Published: August 2024

More than 100 RNA chemical modifications to cellular RNA have been identified. N6-methyladenosine (m6A) is the most prevalent modification of mRNA. RNA modifications have recently attracted significant attention due to their critical role in regulating mRNA processing and metabolism. tRNA and rRNA rank among the most heavily modified RNAs, and their modifications are essential for maintaining their structure and function. With our advanced understanding of RNA modifications, increasing evidence suggests RNA modifications are important in regulating various aspects of insect life. In this review, we will summarize recent studies investigating the impact of RNA modifications in insects, particularly highlighting the role of m6A in insect development, reproduction, and adaptation to the environment.
Rate of speech affects the comprehension of pronouns in children with developmental language disorder
Authors: Abbott Noelle , Nip Ignatius , Love Tracy
Published: August 2024

This study examined whether children with Developmental Language Disorder (DLD) have knowledge of binding principles (i.e., linking pronouns to their structurally licensed antecedent) during real-time sentence processing (cross-modal priming, real-time) and overt comprehension (sentence-picture matching, interpretative) and whether rate of speech impacted access to that knowledge. Fourteen children with DLD participated in two experiments, with sentences presented auditorily at either a regular or slow speech rate. Sentences were matched except to contain a pronoun, reflexive, or noun phrase (control) in the same syntactic position. Experiment (1) used a cross-modal picture priming paradigm to test real-time pronoun-antecedent linking abilities at both rates of speech. Children were instructed to make a binary decision during the uninterrupted auditory presentation of a sentence to a visually presented image (of the antecedent) at the offset of a pronoun, a reflexive, or a control noun. Response times between conditions (e.g., pronoun vs. control noun) were compared to determine whether participants showed evidence of facilitative priming (faster response times in the pronoun than control noun condition) at either speech rate. Experiment (2) used an auditory sentence-picture-matching task to test final comprehension of similar sentences containing a pronoun or reflexive. Accuracy was compared across both speech rates. For Experiment (1), children with DLD did not show evidence of real-time pronoun-antecedent priming at the regular speech rate. However, when sentences were slowed, they showed facilitative priming for the pronoun condition. For experiment (2), children with DLD performed at-chance when interpreting sentences with pronouns regardless of speech rate. While children with DLD have been shown to have difficulty processing sentences containing anaphors (such as pronouns), results suggest that this is not due to loss of intrinsic knowledge of binding principles. By slowing the rate of speech input, we showed that children with DLD do have access to that knowledge and can make the correct link during real-time processing between a pronoun and its structurally licensed antecedent (Experiment 1) but need more time to do so. However, the effect of slowed speech input does not extend to final comprehension (Experiment 2).