bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors regulating incubation temperature and thermal stress in hawksbills in St. Croix, USVI
Authors: Lyons E , D’Alessandro E , Shivlani M , Pollock C , Ewen K
Published: December 2023

The hawksbill sea turtle is listed as Critically Endangered under the IUCN Red List and has been slow to recover in the Caribbean due to historical exploitation and ongoing anthropogenic threats. In turtles, sex and reproductive success are determined by incubation temperatures, whereby lower temperatures produce male hatchlings and higher temperatures produce female hatchlings. As incubation temperatures increase due to climate change, nests are predicted to produce predominantly female hatchlings, threatening sex ratios, reproductive success, and species persistence. One of the largest remaining nesting hawksbill populations within the USA nests on Buck Island. This study aimed to (1) assess the factors driving incubation temperatures and (2) identify the relationship between hatch success and the proportion of time exposed to increasing incubation temperatures. Nest incubation temperatures, beach sector, habitat type, deposition month, percent soil composition, hatch success, and emergence success data were collected from 2019 to 2021. Differences in incubation temperatures across these factors confirmed that the absence of vegetative cover is increasing incubation temperatures on Buck Island, leading to reduced hatchling survival. Results from this study indicate that declines in hatch success may be driven by long-term exposure to temperatures that were previously considered in the literature to be non-lethal to embryos. These findings emphasize the continued need for conservation interventions to protect the future of hawksbills.
Seabird responses to ecosystem changes driven by marine heatwaves in a warming Arctic
Authors: Kuletz KJ , Gall AE , Morgan TC , Prichard AK , Eisner LB , Kimmel DG , De Robertis A , Levine RM , Jones T , Labunski EA
Published: December 2023

In the Pacific Arctic, the Chukchi Sea has been warming for decades, and exhibited an exceptionally warm period from 2015 to 2021. We examined changes in seabird distribution and abundance in the Chukchi Sea, and their relationships to environmental and prey conditions between 2 contrasting periods. We sampled systematically placed stations in late summer during 2 years before (2012, 2013) and 2 years during the warm period (2017, 2019; characterized by multiple marine heatwaves). Ship-based bird counts were used to model at-sea density of 5 seabird foraging guilds relative to oceanographic (water temperature, salinity, chlorophyll) and prey (large copepods, euphausiids, 3 forage fish taxa) variables. Relative to cool years, heatwave years were characterized by warmer, saltier waters, low abundance of large copepods and euphausiids, and elevated fish abundance, including an unprecedented abundance of age-0 walleye pollock Gadus chalcogrammus. Seabird species richness was higher during heatwave years but diversity was lower, driven by an influx of shearwaters. The best models for surface feeding and diving piscivores and diving planktivores included oceanographic and prey variables, plus a heatwave interaction term, indicating that responses to variables differed between cool and heatwave periods, with greatest disparity exhibited by diving planktivores. Models for surface planktivores were inconclusive, whereas shearwater distribution was associated with geographic variables (latitude, distance offshore), with relationships differing during cool and heatwave periods. We propose a conceptual model of how a prolonged period of marine heatwaves may affect the offshore seabird community via changes in prey species composition and distribution.
Exploring the key aspects shaping traditional therapy adoption for stroke treatment: An ethnographic inquiry
Authors: Agianto Agianto , Kamilah Ainun , Agustina Rismia
Published: December 2023

Background: Traditional therapy is commonly utilized for stroke treatment in various communities, including Indonesia. However, there is limited knowledge about the aspects influencing the adoption of traditional medicine for stroke in Indonesia.
Objective: This study aimed to explore the key aspects contributing to the traditional therapy adoption for stroke treatment in Banjarmasin, Indonesia.
Methods: An ethnographic approach was employed, involving seven key informants who were family members of stroke patients. Purposive sampling was used to select the informants. Data were collected through observations, in-depth interviews, and focus group discussions from December 2018 to February 2019 in Banjarmasin, South Kalimantan, Indonesia. Content analysis was utilized for data analysis.
Findings: The study developed seven themes that affected the adoption of traditional therapy for stroke treatment: 1) Role of social media, 2) Desire for recovery and perceived benefits, 3) Economic considerations, 4) Psychological factors and self-motivation, 5) Health insurance and access to healthcare facilities, 6) Cultural influences: Culture, traditions, and community beliefs, and 7) Support from others and therapy logistics.
Conclusion: This study provides important insights into the essential aspects that influence the adoption of traditional therapy for stroke treatment in Indonesia. The findings highlight the need for healthcare policies and practices to consider these aspects to optimize the use of traditional treatment and enhance stroke management outcomes. However, further research is necessary to expand upon these findings, fostering a more comprehensive understanding of the adoption of traditional therapy in stroke treatment.
Anxiety among student nurses in the Philippines: A gender and year-level analysis and its contributing factors in the COVID-19 context
Authors: Pulido Florence L. , Cayabyab Richelle Faith D. , Adversalo Allura Xandra M. , Baylon Alyssa V. , Centeno Aubrey N. , Dizon Aea Jainey G. , Formoso Marc Andrei L. , Hernando Alexis Angel P. , Jucutan Eric Jon Luis B. , Maltu Justine Anthonell G. , Pia Daniel Joy R. , Sally Chaste Priel T. , Tulagan Angeline Ysabelle R.
Published: December 2023

Background: The shift to online learning during the COVID-19 pandemic has raised concerns and heightened anxiety levels, especially among student nurses adapting to academic and clinical challenges.
Objective: This study aimed to assess the anxiety levels of student nurses during the COVID-19 pandemic, examining gender and year-level differences and identifying contributing factors.
Methods: A quantitative descriptive research design was employed, involving 305 student nurses from Levels 1 to 4, selected using proportionate stratified and systematic random sampling at a Philippine nursing school. Data were collected in March 2022 using the Beck Anxiety Inventory (BAI) and a self-made questionnaire. Descriptive and inferential statistics, including frequencies, percentages, means, Independent t-tests, and ANOVA, were utilized with a significance level of 0.05.
Results: The mean anxiety level among student nurses was 1.61, significantly differing by year level and gender (p <0.05). The most contributing factor of anxiety was ‘the adjustments to make with the sudden change of face-to-face classes to online or distance learning mode’ (90.16%), while the least factor was ‘lack of financial sources' (46.23%).
Conclusion: Student nurses had moderate anxiety levels, with gender and year level as significant contributing factors. Female student nurses experienced higher anxiety levels than males, and lower-level students experienced greater anxiety than their higher-level counterparts. Various factors, including academic, social, financial, and perceived health risk-related factors, affected student nurses’ anxiety levels, with academic-related factors having the most significant impact and financial-related factors having the least impact.
Tradition meets controversy: Ida Dayak’s phenomenon and its implications in healing practice and healthcare policy
Authors: Gunawan Joko
Published: December 2023

N/A
Exploring the professional development needs of nurse educators in Saudi Arabia: A cross-sectional survey
Authors: Alharsan Mai Salem , Abdelhafez Amal Ismael
Published: December 2023

Background: Professional development for nurse educators is essential to ensure that nursing students receive high-quality education and can provide effective patient care. However, nurse educators in Saudi Arabia encounter numerous challenges, emphasizing the need for tailored career development opportunities.
Objective: This study aimed to identify the professional development needs of nurse educators within Saudi university nursing programs.
Methods: A quantitative cross-sectional survey was employed in April 2023, involving 121 nurse educators selected through convenience sampling. The study consisted of nursing colleges and departments at 15 government-operated Saudi universities. Data were collected on April 2023 through questionnaires and analyzed using descriptive statistics and correlational analysis.
Results: Among participants, 45 (37.2%) had 6 to 10 years of teaching experience. Evaluating learning (76.9%) was the most frequently identified Professional Faculty Development Need in teaching skills. Writing articles and abstracts (73.6%) were commonly identified in scholarly development, while presentation software for teaching (79.3%) dominated technology use development. The most preferred method for taking a development program was 1–2-hour sessions (81%). Significant differences in professional needs based on years of academic experience and academic rank were observed (p <0.05).
Conclusion: The study identified various terms related to nurse educators’ perceived development needs. Educator development and educational specialists must consider both overlapping and unique requirements of different health science schools in planning professional development. Crucial skills highlighted in the study include cross-cultural teaching strategies, course design, large group teaching, conflict management, negotiation, and team-building for administrative work and career development.
PENGENALAN CERITA RAKYAT LOKAL MELALUI KEGIATAN LITERASI DI SEKOLAH DASAR
Authors: Mastiah Mastiah , Ahmad Khoiri
Published: December 2023

Kegiatan Pengabdian kepada Masyarakat ini bertujuan mengenalan cerita rakyat lokal Kabupaten melalui kegiatan literasi di sekolah dasar dimana siswa-siswi sekolah dasar di Kabupaten Melawi belum mengenal cerita rakyat lokal Kabupeten Melawi. Metode pelaksanaan ini dilakukan dengan sosialisasi, observasi, dan dokumentasi. Adapun hasilnya menunjukkan bahwa kegiatan literasi dengan memanfaatkan cerita rakyat lokal, dalam hal ini Melawi, perlu terus digalakkan. Hal ini karena selain menggiatkan literasi di sekolah dasar, juga dapat mengenalkan cerita rakyat lokal kepada siswa-siswi di sekolah, terutama sekolah dasar. Siswa-siswi sekolah dasar Kabupaten Melawi mengetahui dan memahami cerita-cerita rakyat lokal yang ada di Kabupaten Melawi. Siswa-siswi sekolah dasar Kabupaten Melawi dapat memahami nilai-nilai yag teradapat dalam cerita rakyat Kabupten Melawi. Kegiatan literasi di sekolah dasar dapat memanfaatkan cerita-cerita rakyat lokal di Kabupaten Melawi, sehingga dapat membantu melestarikan cerita-cerita rakyat lokal.
Legislative Process: Essential Characteristics, Influencing Factors
Authors: Tarakhonych T. I.
Published: December 2023

In this paper, the author analyzes various approaches to understanding the legislative process, its interrelation with related categories such as lawmaking and legislative processes.

It is emphasized that the use of the term «legislative process» indicates the presence of an intellectual component in the corresponding subjects’ activities, while referring to the «lawmaking process» gives preference to the official and governmental aspect of this process.

The peculiarities of the legislative process are identified, namely: it is a type of lawmaking activity, characterized by a phased implementation, closely linked to legal reality, exhibiting a systematic and structured nature, indicating its classification as a social system, having functional orientation and being based on certain principles, with a characteristic composition of subjects aimed at the adoption, modification, suspension, or repeal of relevant legal norms.

It is emphasized that the legislative process is a specific type of lawmaking activity carried out by certain subjects, characterized by phased implementation, functionality, and aimed at the adoption, modification, suspension, or repeal of relevant legal norms.

The author highlights that among the essential characteristics of the legislative process, ensuring its effectiveness holds significant importance.

The factors for improving the quality and effectiveness of legislative activities are identified and characterized, including attention to general social, organizational, and legal factors.

Key words: lawmaking, legislative process, lawmaking process, influencing factors, effectiveness of the legislative process, optimization of the legislative process, factors that influence the formation of the lawmaking process.
MARTIYA UÇMAYI ÖĞRETEN KEDİ BAŞLIKLI ÇOCUK KİTABINA EKOELEŞTİREL BİR BAKIŞ
Authors: DURAN Zeliha
Published: December 2023

Günümüzde denizlerin kirletilmesi, türlerin yok oluşu, ormanların yok edilmesi, su kaynaklarının tükenmesi, toprağın, havanın ve suyun kirletilmesi gibi çevre sorunları korkutucu boyutlara ulaşmıştır. Ekolojik sorunların ana sebebi insanın, kendisini doğadan soyutlayarak ona egemen olma isteğidir. Ego merkezli bu görüş neticesinde insan, doğayı sınırsızca sömürebileceği öteki olarak konumlandırmıştır. Çevre sorunlarına karşı edebiyatın bir tepkisi olarak ortaya çıkan ekoeleştirinin en temel amacı, insan merkezcilikten uzak bir doğa anlayışının gelişmesidir. Edebiyatın insanların düşünce yapılarının değişmesi konusundaki önemi dikkate alındığında ekolojik düşünce çerçevesinde yazılan metinlerin önemi daha iyi anlaşılmaktadır. Özellikle çocuk kitaplarının eko-merkezli bir bakışla kaleme alınması doğaya karşı duyarlı ve bilinçli bireyler yetiştirme konusunda oldukça önemlidir. Benzer şekilde açıkça bir doğa göstergesi olmayan metinlerde ekoeleştirel okumalar yapmak da konu hakkında bilinçlendirme noktasında değerlidir. Bu çalışmada Şilili yazar Luis Sepúlveda’nın Türkçeye Martıya Uçmayı Öğreten Kedi başlığıyla çevrilen çocuk kitabı ekoeleştiri kuramı çerçevesinde incelenmiştir. Denizleri petrolle kirleten insan yüzünden bir martının ölmesiyle başlayan hikâye, insan merkezli bakış açısını eleştirir. Kitap, doğada ikincilleştirilen insan dışı varlıklara farklı bir gözle bakmayı sağlar. İnsanların ekosistemde kendileri dışındaki varlıklara gösteremedikleri saygı ve sevgiyi kitaptaki hayvan karakterler gösterir. Anlatı boyunca insan, uzak durulması gereken tehlikeli bir varlık olarak betimlenir. Kitap aracılığıyla çocuklara ekosistemdeki her varlığın kendi başına değerli olduğu, ekosistem içinde her şeyin birbirine bağlı olduğu ve insanın ekosistemin sadece bir parçası olduğu gibi önemli mesajlar iletilir.
ÇOBANLIĞIN DİJİTAL DÖNÜŞÜMÜ: YOUTUBER ÇOBAN ORHUN TOPKAYA
Authors: BÜYÜKOKUTAN TÖRET Aslı , SÖĞÜT Zülal
Published: December 2023

Türk kültüründe geleneksel bir meslek olan çobanlık, son yıllarda mesleğin icra edilmemesi nedeniyle yok olup gitme tehlikesi altındadır. Kentleşme, modernleşme ve endüstrileşme süreci bunda etkilidir. Söz konusu geleneksel mesleğin devamlılığı adına, çobanlık kültürünün dijital ortamlarda yeniden canlandırılmaya çalışılması anlamlıdır. Başta YouTube olmak üzere çeşitli çevrim içi platformlar, çobanlık mesleğine dair kültürün kayıt altına alınması ve yeni nesle tanıtılması açısından dikkat çekicidir. Eskişehirli çoban Orhun Topkaya’nın, kendi gündelik hayatını ve çobanlıkla ilgili deneyimlerini paylaştığı YouTube kanalı bulunmaktadır. Yazıda, Orhun Topkaya’nın YouTube kanalı ve bu kanalda çobanlık mesleğinin ve kültürünün aktarımı hakkında bilgi verilmiştir. Orhun Topkaya, kendi ismiyle açmış olduğu YouTube kanalında video bloglar aracılığıyla çobanlık kültürünü tanıtmaktadır. Özellikle çobanlık mesleğinin icrasında başvurduğu yenilikler ve uyguladığı teknolojiler, çobanlığa dair birtakım olumsuz ön yargıları kırabilecek niteliktedir. Bunun yanında, Orhun Topkaya’nın teknolojik yeniliklerin çobanlık mesleğine de uygulanabileceği göstermesi, mesleğin koşullarında iyileştirmelerin mümkün olduğunu ortaya koymaktadır. Yapılan incelemeler sonucunda; Orhun Topkaya’nın, YouTube kanalında bir taraftan çobanlığa dair geleneksel yaşam tarzının önemini vurgularken diğer taraftan teknolojinin sunduğu imkânlarla daha fazla insanın bu kültüre erişimini sağladığı görülmüştür. Bu durum, çobanlık mesleğinin gelecek nesillere sevdirilmesi noktasında işlevseldir. Ayrıca Topkaya’nın mesleğin icrasını YouTube ortamına taşımakla gerçekleştirdiği değişim, çobanlığın geçirdiği dijital dönüşümü göstermesi bakımından da önem arz etmektedir.
MUSA DAĞ ERMENİLERİ, 1915–1939: BİR AYAKLANMA VE KAÇIŞ HİKAYESİ
Authors: YEŞİLBURSA Behçet Kemal
Published: December 2023

Bu kitap, Ermeni topluluklarının 1915 ile 1939 yılları arasında Musa Dağ'daki isyanını ve kaçışını inceliyor. Ermenilerin Osmanlı İmparatorluğu'na karşı isyanını çevreleyen anlatıları, imparatorluğun tehcir düzenine karşı direnişi ve Musa Dağı'na kaçış analiz ediyor.
ACENTENİN SIR SAKLAMA YÜKÜMLÜLÜĞÜNÜN KAYNAĞI, KONUSU VE SÜRESİ
Authors: Bahar Sayın Hediye
Published: December 2023

6102 sayılı Türk Ticaret Kanunu’nun (TTK) 102 ilâ 123 üncü maddelerinde acente düzenlenmektedir. TTK ve acentelik sözleşmesi gereği acente, faaliyetini yerine getirirken pek çok borç ve yükümlülük altındadır. Bu yükümlülüklerin bazıları TTK’da açık şekilde düzenlenmiştir. Ancak TTK’da acentenin sır saklama yükümlülüğü açık şekilde düzenlenmemiştir. Sır, gizli kalması sahibine menfaat sağlayan, sahibinin başkaları tarafından öğrenilmesini istemediği bilgidir. Sır sahibinin sır üzerinde maddi ve manevi menfaati olması sebebiyle, tacir yardımcılarından biri olan acentenin müvekkili ile ilişkisinde sır saklama yükümlülüğünün mevcut olup olmadığı ve mevcut ise bu yükümlülüğün hukuki kaynağının tespit edilmesi gerekmektedir. Bu makalede; acentenin sır saklama yükümlülüğünün hukuki kaynağı, yükümlükle bağlantılı düzenlemeler, yükümlülüğün konusu ve süresi belirlenmeye çalışılmıştır.
A CIE change in our understanding of endocytic mechanisms
Authors: Rioux Daniel J. , Prosser Derek C.
Published: December 2023

The past six decades have seen major advances in our understanding of endocytosis, ranging from descriptive studies based on electron microscopy to biochemical and genetic characterization of factors required for vesicle formation. Most studies focus on clathrin as the major coat protein; indeed, clathrin-mediated endocytosis (CME) is the primary pathway for internalization. Clathrin-independent (CIE) pathways also exist, although mechanistic understanding of these pathways remains comparatively elusive. Here, we discuss how early studies of CME shaped our understanding of endocytosis and describe recent advances in CIE, including pathways in model organisms that are poised to provide key insights into endocytic regulation.
Impact of cardiac rehabilitation on pre- and post-operative transcatheter aortic valve replacement prognoses
Authors: Zou Jieru , Yuan Jie , Liu Jingjin , Geng Qingshan
Published: December 2023

Transcatheter aortic valve replacement (TAVR) is a relatively new treatment method for aortic stenosis (AS) and has been demonstrated to be suitable for patients with varying risk levels. Indeed, among high-risk patients, TAVR outcomes are comparable to, or even better, than that of the traditional surgical aortic valve replacement (SAVR) method. TAVR outcomes, with respect to post-surgical functional capacity and quality of life, have also been found to be improved, especially when combined with cardiac rehabilitation (CR). CR is a multidisciplinary system, which integrates cardiology with other medical disciplines, such as sports, nutritional, mind-body, and behavioral medicine. It entails the development of appropriate medication, exercise, and diet prescriptions, along with providing psychological support, ensuring the cessation of smoking, and developing risk factor management strategies for cardiovascular disease patients. However, even with CR being able to improve TAVR outcomes and reduce post-surgical mortality rates, it still has largely been underutilized in clinical settings. This article reviews the usage of CR during both pre-and postoperative periods for valvular diseases, and the factors involved in influencing subsequent patient prognoses, thereby providing a direction for subsequent research and clinical applications.
Comparison of problem-based and team-based learning strategies: a multi-institutional investigation
Authors: Koriťáková Eva , Jivram Trupti , Gîlcă-Blanariu Georgiana-Emmanuela , Churová Vendula , Poulton Ella , Ciureanu Adrian Ioan , Louis Chandran , Ștefănescu Gabriela , Schwarz Daniel
Published: December 2023

Objectives

Over time, pedagogical practices in higher education have evolved significantly, which has led to the development of collaborative learning strategies. The study aims to compare the two most prominent ones – problem-based learning (PBL) and team-based learning (TBL). The comparison, integrated with Virtual Scenarios (VSs), involves student cohorts from various European institutions, specifically focusing on both PBL and TBL methods. The study is distinctive in its use of a consistent PBL/TBL methodology, ensured via joint staff training, and explores the perspectives of students and educators on these learning techniques. The overarching aim is to examine how PBL and TBL, coupled with VSs, influence problem-solving skills, independent learning, and student engagement.

Methods

The examination was made using feedback from 399 students and 11 tutors collected in four trials held in three institutions based in Czechia, the United Kingdom and Romania. The data gathered from surveys and a focus group discussion contained qualitative as well as quantitative data, such as Likert scale questions. To analyse the overall trends in learners’ satisfaction with PBL and TBL sessions, the mean score calculated from the transformed Likert scale questions was compared between sessions and among institutions using multivariate ANOVA.

Results

The students’ satisfaction and learning experience are heavily influenced by specific conditions, primarily their prior experience, room and technical set-up, group composition and especially the personality of a tutor. Overall, both strategies were found to be well-received by students used to traditional teaching methods. Students accustomed to PBL did not find TBL more engaging or useful. The identified advantages of TBL over PBL were the presence of a content expert, readiness tests, acquiring the same knowledge ensured through the collective presence of all students in one session and unified pre-class materials. However, TBL is more demanding on room set-up and teaching staff coordination.

Conclusion

Both strategies have been found to have pros and cons and neither showed clear superiority over the other one. An institution newly implementing PBL or TBL needs to focus on different aspects than an institution planning to switch from PBL to TBL.
Exposure of marine megafauna to cumulative anthropogenic threats in north-west Australia
Authors: Ferreira Luciana C. , Thums Michele , Whiting Scott , Meekan Mark , Andrews-Goff Virginia , Attard Catherine R. M. , Bilgmann Kerstin , Davenport Andrew , Double Mike , Falchi Fabio , Guinea Michael , Hickey Sharyn M. , Jenner Curt , Jenner Micheline , Loewenthal Graham , McFarlane Glenn , Möller Luciana M. , Norman Brad , Peel Lauren , Pendoley Kellie , Radford Ben , Reynolds Samantha , Rossendell Jason , Tucker Anton , Waayers David , Whittock Paul , Wilson Phillipa , Fossette Sabrina
Published: December 2023

As the use of coastal and offshore environments expands, there is a need to better understand the exposure of marine megafauna to anthropogenic activities that potentially threaten their populations. Individual satellite telemetry studies are often hampered by small sample sizes, providing limited information on spatiotemporal distributions of migratory animals and their relationships to anthropogenic threats. We addressed this issue by synthesising satellite tracking data from 484 individuals of three taxonomic groups and six species; three marine turtle, two whale and one shark. The spatial overlap between taxa distributions and multiple anthropogenic activities was assessed as a proxy for the cumulative exposure of these taxa to anthropogenic threats (coastal modification, vessel strike, underwater noise, oil spill, bycatch, entanglement, and artificial light) across an area totalling 2,205,740 km2 off north-western Australia. Core exposure areas (top 50% of the distribution) encompassed ecologically important sites for all taxa, such as the Ningaloo and Pilbara regions, migratory routes for whales and sharks in offshore waters beyond Ningaloo Reef, and marine turtle nesting beaches at Barrow Island and Cape Lambert. Although areas of high exposure represented <14% of taxa distributions, we showed that no taxa occurred in the absence of threats and that even areas with existing spatial protections are experiencing high levels of exposure. Importantly, we developed a robust approach for documenting the potential exposure of marine species to a range of human activities at appropriate spatial scales to inform conservation management.
Novel enhancer mediates the RPL36A-HNRNPH2 readthrough loci and GLA gene expressions associated with fabry disease
Authors: Al-Obaide Mohammed A. , Islam Saimul , Al-Obaidi Ibtisam , Vasylyeva Tetyana L.
Published: December 2023

Fabry disease (FD) is a rare genetic condition caused by mutations in the GLA gene, located on the X chromosome in the RPL36-HNRNPH2 readthrough genomic region. This gene produces an enzyme called alpha-galactosidase A (α-Gal A). When the enzyme does not function properly due to the mutations, it causes harmful substances called globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to build up in the body’s lysosomes. This accumulation can damage the kidneys, heart, eyes, and nervous system. Recent studies have shown that the RPL36A-HNRNPH2 readthrough loci, which include RPL36A and HNRNPH2 genes, as well as the regulatory sequence known as the GLA-HNRNPH2 bidirectional promoter, may also play a role in FD. However, the involvement of enhancer RNAs (eRNAs) in FD is still poorly understood despite their known role in various diseases. To investigate this further, we studied an RPL36A enhancer called GH0XJ101390 and showed its genomic setting in the RPL36-HNRNPH2 readthrough region; the eRNA is rich in Homotypic Clusters of TFBSs (HCTs) type and hosts a CpG Island (CGI). To test the functional correlation further with GLA, RPL36A, and HNRNPH2, we used siRNAs to knock down GH0XJ101390 in human kidney embryonic cells 293T. The results showed a significant decrease in RPL36A and GLA expression and a non-significant decrease in HNRNPH2 expression. These findings could have important implications for understanding the regulatory mechanisms of GH0XJ101390 and its potential role in FD. A better understanding of these mechanisms may improve diagnostic and therapeutic methods for FD, which could ultimately benefit patients with this rare condition.
Retrospective clinical and genetic analysis of COL6-RD patients with a long-term follow-up at a single French center
Authors: Morel Victor , Audic Frédérique , Tardy Charlotte , Verschueren Annie , Attarian Shahram , Nguyen Karine , Salort-Campana Emmanuelle , Krahn Martin , Chabrol Brigitte , Gorokhova Svetlana
Published: December 2023

Collagen type VI-related dystrophies (COL6-RD) are rare diseases with a wide phenotypic spectrum ranging from severe Ullrich’s congenital muscular dystrophy Ullrich congenital muscular dystrophy to much milder Bethlem myopathy Both dominant and recessive forms of COL6-RD are caused by pathogenic variants in three collagen VI genes (COL6A1, COL6A2 and COL6A3). The prognosis of these diseases is variable and difficult to predict during early disease stages, especially since the genotype-phenotype correlation is not always clear. For this reason, studies with long-term follow-up of patients with genetically confirmed COL6-RD are still needed. In this study, we present phenotypic and genetic data from 25 patients (22 families) diagnosed with COL6-RD and followed at a single French center, in both adult and pediatric neurology departments. We describe three novel pathogenic variants and identify COL6A2:c.1970-9G>A as the most frequent variant in our series (29%). We also observe an accelerated progression of the disease in a subgroup of patients. This large series of rare disease patients provides essential information on phenotypic variability of COL6-RD patients as well as on frequency of pathogenic COL6A gene variants in Southern France, thus contributing to the phenotypic and genetic description of Collagen type VI-related dystrophies.
Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program
Authors: Armstrong Nicole D. , Srinivasasainagendra Vinodh , Ammous Farah , Assimes Themistocles L. , Beitelshees Amber L. , Brody Jennifer , Cade Brian E. , Ida Chen Yii-Der , Chen Han , de Vries Paul S. , Floyd James S. , Franceschini Nora , Guo Xiuqing , Hellwege Jacklyn N. , House John S. , Hwu Chii-Min , Kardia Sharon L. R. , Lange Ethan M. , Lange Leslie A. , McDonough Caitrin W. , Montasser May E. , O’Connell Jeffrey R. , Shuey Megan M. , Sun Xiao , Tanner Rikki M. , Wang Zhe , Zhao Wei , Carson April P. , Edwards Todd L. , Kelly Tanika N. , Kenny Eimear E. , Kooperberg Charles , Loos Ruth J. F. , Morrison Alanna C. , Motsinger-Reif Alison , Psaty Bruce M. , Rao Dabeeru C. , Redline Susan , Rich Stephen S. , Rotter Jerome I. , Smith Jennifer A. , Smith Albert V. , Irvin Marguerite R. , Arnett Donna K.
Published: December 2023

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data.

Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American).

Results: One variant in the known HTN locus, KCNK3, was a top finding in the multi-ethnic analysis (p = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74–0.88)]. This variant was replicated in the Vanderbilt University Medical Center’s DNA repository data. Aggregate gene-based signals included the genes AGTPBP, MYL4, PDCD4, BBS9, ERG, and IER3.

Discussion: Additional work validating these loci in larger, more diverse populations, is warranted to determine whether these regions influence the pathobiology of aTRH.
First case report of a novel KIF13A-ALK fusion in a lung adenocarcinoma patient and response to alectinib with a 4-year follow-up
Authors: Mo Zheng , Cai Cunliang , Yao Jingjing , Zhao Jingquan , Zhang Mingqiang , Liu Hao , Mu Xiangdong
Published: December 2023

The prevalence of Anaplastic Lymphoma Kinase gene (ALK) fusion is about 5% among patients with lung adenocarcinoma, underscoring the importance of pinpointing distinct fusion variants for optimizing treatment approaches. This is the first reported case of a 74-year-old female with stage IV lung adenocarcinoma, featuring a novel Kinesin Family Member 13A (KIF13A)-ALK fusion, identified via next-generation sequencing (NGS) and confirmed with fluorescence in situ hybridization (FISH). Initially undergoing chemotherapy and then crizotinib, she achieved a partial response (PR) before progressing with multiple bone metastases. However, subsequent treatment with alectinib as a third-line option yielded positive results. A stable disease state persisted for an impressive 31 months of progression-free survival (PFS), accompanied by minimal toxicity symptoms. Up until now, a remarkable near 4-year span of overall survival (OS) has been consistently observed and monitored. This report of a KIF13A-ALK fusion case benefit significantly from alectinib with extensive follow-up. The case diversifies the array of ALK fusion partners and holds clinical relevance in refining therapeutic choices for KIF13A-ALK fusion-associated lung cancer.
Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis
Authors: Okurut Samuel , Boulware David R. , Okafor Elizabeth , Rhein Joshua , Kajumbula Henry , Bagaya Bernard S. , Bwanga Freddie , Olobo Joseph O. , Manabe Yukari C. , Meya David B. , Janoff Edward N.
Published: December 2023

Introduction

Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, particularly among women, despite the currently optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system [brain, spinal cord, and cerebrospinal fluid (CSF)] elicits the local production of cytokines, chemokines, and other biomarkers. However, no consistent diagnostic or prognostic neuroimmune signature is reported to underpin the risk of death or to identify mechanisms to improve treatment and survival. We hypothesized that distinct neuroimmune signatures in the CSF would distinguish survivors from people who died on antifungal treatment and who may benefit from tailored therapy.

Methods

We considered baseline clinical features, CSF cryptococcal fungal burden, and CSF neuroimmune signatures with survival at 18 weeks among 419 consenting adults by “gender” (168 women and 251 men by biological sex defined at birth).

Results

Survival at 18 weeks was significantly lower among women than among men {47% vs. 59%, respectively; hazard ratio (HR) = 1.4 [95% confidence interval (CI), 1.0 to 1.9; p = 0.023]}. Unsupervised principal component analysis (PCA) demonstrated divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, women had lower levels of programmed death ligand 1, Interleukin (IL) (IL-11RA/IL-1F30, and IL-15 (IL-15) than men (all p < 0.028). Female survivors compared with those who died expressed significant elevations in levels of CCL11 and CXCL10 chemokines (both p = 0.001), as well as increased T helper 1, regulatory, and T helper 17 cytokines (all p < 0.041). In contrast, male survivors expressed lower levels of IL-15 and IL-8 compared with men who died (p < 0.044).

Conclusions

Survivors of both genders demonstrated a significant increase in the levels of immune regulatory IL-10. In conclusion, the lower survival among women with CM was accompanied by distinct differential gender-specific neuroimmune signatures. These female and male intragender-specific survival–associated neuroimmune signatures provide potential targets for interventions to advance therapy to improve the low survival among people with HIV-associated CM.
Unique characteristics of the tumor immune microenvironment in young patients with metastatic colorectal cancer
Authors: Griffith Brian D. , Lazarus Jenny , McGue Jake , Krishnan Santhoshi , D’Angelica Michael I. , Shia Jinru , Dobrosotskaya Irina , Shi Jaiqi , Edwards Jacob , Rao Arvind , Frankel Timothy L.
Published: December 2023

Introduction

Metastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME).

Methods

111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those <50 years or >65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement.

Results

There was no difference in infiltration or proportion of immune cells based upon age, but the younger cohort had a higher proportion of programmed death-ligand 1 (PD-L1)+ expressing antigen presenting cells (APCs) and demonstrated decreased intercellular distance and increased cellular engagement between tumor cells (TCs) and cytotoxic T lymphocytes (CTLs), and between TCs and APCs. These trends were independent of microsatellite instability in tumors.

Discussion

Age-related differences in PD-L1 expression and cellular engagement in the tumor microenvironment of patients with mCRC, findings which were unrelated to microsatellite status, suggest a more active immune microenvironment in younger patients that may offer an opportunity for therapeutic intervention with immune based therapy.
The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways
Authors: Chen Yu , Guo De-zhi , Zhu Cheng-long , Ren Shi-chun , Sun Chen-yan , Wang Yi , Wang Jia-feng
Published: December 2023

Sepsis currently remains a major contributor to mortality in the intensive care unit (ICU), with 48.9 million cases reported globally and a mortality rate of 22.5% in 2017, accounting for almost 20% of all-cause mortality worldwide. This highlights the urgent need to improve the understanding and treatment of this condition. Sepsis is now recognized as a dysregulation of the host immune response to infection, characterized by an excessive inflammatory response and immune paralysis. This dysregulation leads to secondary infections, multiple organ dysfunction syndrome (MODS), and ultimately death. PD-L1, a co-inhibitory molecule expressed in immune cells, has emerged as a critical factor in sepsis. Numerous studies have found a significant association between the expression of PD-1/PD-L1 and sepsis, with a particular focus on PD-L1 expressed on neutrophils recently. This review explores the role of PD-1/PD-L1 in immunostimulatory and anti-inflammatory pathways, illustrates the intricate link between PD-1/PD-L1 and sepsis, and summarizes current therapeutic approaches against PD-1/PD-L1 in the treatment and prognosis of sepsis in preclinical and clinical studies.
Temporal uncoupling between demographic and genetic metrics in fisheries assessment: the European hake case study
Authors: Fernández-Míguez María , Pita Alfonso , Gómez Antonio , Presa Pablo
Published: December 2023

An authentic ecological transition for fisheries sustainability requires the integration of all relevant biological criteria in assessment models. Current analyses aim to dissect the evolution of some demographic and genetic metrics in the overharvested Southern European hake fishery in the last four decades. Demographic data were drawn from the official records of ICES, while genetic data were obtained from a lustrum-based sampling series between 1975 and 2014. Opposite to Non-Adaptive Polymorphic Systems (NAPS) microsatellites, Adaptive Polymorphic Systems (APS) microsatellites succeeded at detecting genetic erosion at the maximum population overharvest in lustrum 1996–2000, a phenomenon also confirmed with the molecular variation of the mtDNA cytochrome b gene. We show that the maximum demographic mortality Z_NSSB (1986–1990) predated both the maximum genetic effective mortality Z_LDNe (1991–1995) as well as the maximum cohort-based mortality Z¯_ICES (1996–2000). Such temporal uncoupling between demographic and genetic metrics suggests that official cohort analyses are far from assessing the real biological status of the Southern European hake fishery to achieve its sustainability-oriented advice.
The general public’s attitude towards accepting payment for kidney donation
Authors: Gonen Limor Dina , Bokek-Cohen Ya’arit , Tarabeih Mahdi
Published: December 2023

Introduction

Kidney transplantation has become the most cost-effective treatment for patients with end-stage kidney disease (ESKD) and offers them the highest quality of life. Yet, kidney donation is often inaccessible due to cultural and traditional beliefs about organ donation. The goal of our study is to assess the value of kidney donation using the Willingness to Accept (WTA) technique. We also aim to understand the factors influencing an individual’s willingness to donate an organ.

Methods

A self-administered survey was completed by 985 participants from the general public. The quantitative method and survey design that were chosen used descriptive, correlational, nonparametric, and multivariate statistical tests.

Results

Most of the respondents, 895 (90.9%) are not willing to donate a kidney while alive. Four hundred and five (41.1%) of the respondents are not willing to donate a kidney after their death, while the rest are willing to donate their kidney after their death without financial compensation. The same attitude applies to the donation of a kidney from their relatives. Significant predictors from the results of the logistic regression model in predicting the lowest (minimal) amount that will encourage donation of one kidney after death were: Marital status; Nationality; Adi card holder; Knowing people who need a kidney donation; confidence in the medical staff; and consideration of the family’s opinions regarding organ donation.

Discussion

Using cost benefit analysis (CBA), with the aim of evaluating the willingness of individuals to accept payment for innovative medical procedures, such as kidney donation, allows an assessment of the perceived value of the medical procedure and enables policymakers to decide whether to allocate funds or offer subsidies for kidney donation, given the limited healthcare resources available. During our research, we found that most participants did not support the commercialization of organs. Our recommendation for policymakers and health professionals is to continue providing adequate funding for kidney donations and to implement educational programs aimed at improving attitudes towards organ donation.
Periodontitis relates to benign prostatic hyperplasia via the gut microbiota and fecal metabolome
Authors: Guo Xing-Pei , Yang Jun , Wu Lan , Fang Cheng , Gu Jia-Min , Li Fei , Liu Han-Song , Li Lu-Yao , Wang Shuang-Ying
Published: December 2023

Objectives

Periodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear.

Methods

We established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).

Results

Sequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens.

Conclusion

Our study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.
Identification of the human cerebral cortical hemodynamic response to passive whole-body movements using near-infrared spectroscopy
Authors: Zhao Yue , Wei Yue , Wang Yixuan , So Richard H. Y. , Chan Chetwyn C. H. , Cheung Raymond T. F. , Wilkins Arnold
Published: December 2023

The human vestibular system is crucial for motion perception, balance control, and various higher cognitive functions. Exploring how the cerebral cortex responds to vestibular signals is not only valuable for a better understanding of how the vestibular system participates in cognitive and motor functions but also clinically significant in diagnosing central vestibular disorders. Near-infrared spectroscopy (NIRS) provides a portable and non-invasive brain imaging technology to monitor cortical hemodynamics under physical motion.

Objective

This study aimed to investigate the cerebral cortical response to naturalistic vestibular stimulation induced by real physical motion and to validate the vestibular cerebral cortex previously identified using alternative vestibular stimulation.

Approach

Functional NIRS data were collected from 12 right-handed subjects when they were sitting in a motion platform that generated three types of whole-body passive translational motion (circular, lateral, and fore-and-aft).

Main results

The study found that different cortical regions were activated by the three types of motion. The cortical response was more widespread under circular motion in two dimensions compared to lateral and fore-and-aft motions in one dimensions. Overall, the identified regions were consistent with the cortical areas found to be activated in previous brain imaging studies.

Significance

The results provide new evidence of brain selectivity to different types of motion and validate previous findings on the vestibular cerebral cortex.
TRPML1 as a potential therapeutic target for triple-negative breast cancer: a review
Authors: Pan Ying , Zhao Qiancheng , He Haitao , Qi Yubo , Bai Yujie , Zhao Jia , Yang Yiming
Published: December 2023

Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer, and effective treatments are urgently needed owing to its poor prognosis. Surgery, radiotherapy, and chemotherapy, alone or in combination, are the leading choices for TNBC therapy. Although promising approaches and procedures have emerged, several challenges, such as off-target effects, drug resistance, and severe side effects, remain to be addressed. Recently, transient receptor potential channel mucolipin 1 (TRPML1) has attracted the attention of researchers because its expression has been implicated in numerous diseases, including cancer. TRPML1 regulates biological events and signaling pathways, including autophagic flux, exocytosis, ionic homeostasis, and lysosomal biogenesis, all contributing to tumorigenesis and cancer progression. TRPML1 also functions as a building block for cancer cell growth, mitogenic signaling, priming tissues for metastasis, and activation of transcriptional programs, processes involved in several malignant tumors. This review provides an overview of breast cancer epidemiology and diagnostic techniques and then discusses the existing therapeutics. Additionally, we elaborate on the development of, and associated challenges to, TNBC diagnostics and treatment and the feasibility of TRPML1 as a therapeutic target for TNBC.