bluuebunny/crossref_metadata_2025 huggingface dataset:
Okul Dışı Öğrenme Ortamı Uygulamalarının Öğrencilerin Matematik Başarılarına Etkisi ve Uygulamaya İlişkin Görüşleri
Authors: Usta Neslihan , Gürçay Sevdenur , Sakioğlu Şükran Nur , Demir Fatma
Published: September 2023

Bu araştırmanın amacı, okul dışı öğrenme ortamında yapılan uygulamanın ortaokul öğrencilerinin ondalık gösterim konusundaki akademik başarılarına ve öğrenci görüşlerine etkisinin incelenmesidir. Araştırma Batı Karadeniz Bölgesi’nin bir ilinde MEB’e bağlı bir devlet ortaokulunun 5. sınıf öğrencileri ile gerçekleştirilmiştir. Deney grubu ve kontrol grubu kullanılan araştırmada deney grubunda 12, kontrol grubunda 16 öğrenci bulunmaktadır. Deney grubuna okul dışı öğrenme ortamı olan Kermes etkinliği yapılmış, kontrol grubuna ise mevcut Matematik Öğretim Programı’nın (MEB, 2018) önerdiği şekilde uygulama yapılmıştır. Araştırmanın nicel yaklaşımına dayalı olarak yapılan bölümünde araştırma deseni olarak kontrol gruplu ön test son test yarı deneysel desen kullanılmıştır. Her iki gruba da Matematik Başarı Ön Testi uygulamadan önce, Matematik Başarı Son Testi uygulamadan sonra birer kez uygulanmıştır. Öğrencilerin kermes etkinliğine ilişkin görüşlerinin incelenmesi sürecinde Yarı Yapılandırılmış Görüşme Formu kullanılmıştır ve analizi içerik analiz ile yapılmıştır. Araştırma sonucunda kermes etkinliği uygulamasının öğrencilerin ondalık gösterimi verilen sayılarla toplama ve çıkarma işlemlerini yapabilme başarılarına olumlu etki ettiği görülmüştür. Bu araştırmanın sonuçları ile matematik derslerinde okul dışı öğrenme ortamlarının kullanılması önerilebilir.
Montessori Uygulayıcısı Erken Çocukluk Dönemi Eğitimcilerinin Bilimsel Süreç Becerilerinin Kazandırılmasına İlişkin Görüş ve Uygulamalarının İncelenmesi
Authors: Özbey Dilara , Kutluca Ali Yiğit
Published: September 2023

Bu araştırmanın amacı, Montessori uygulayıcısı erken çocukluk dönemi eğitimcilerinin bilimsel süreç becerilerinin kazandırılmasına ilişkin görüş ve uygulamalarını incelemektir. Montessori uygulayıcısı üç okul öncesi öğretmeni ve iki usta öğreticinin katıldığı bu araştırma durum çalışması deseninde gerçekleştirilmiştir. Katılımcılar, amaçlı örneklem yöntemlerinden biri olan ölçüt örneklemeye göre belirlenmiştir. Veriler, ders planı yapılandırma formu, bilimsel süreç becerileri görüşme soruları ve sınıf içi gözlem formu aracılığıyla toplanmıştır. Ders planları ve görüşme soruları aracılığıyla toplanan veriler üzerinde tümevarımsal içerik analizi yapılmıştır. Sınıf içi gözlemler ise analitik bir gözlem protokolü yardımıyla analiz edilmiştir. Bulgular, erken çocukluk dönemi eğitimcilerinin gözlem, tahmin etme, sınıflama, ölçme ve çıkarım yapma becerisini kazandırma eğiliminde olduklarını ortaya çıkarmıştır. Ayrıca katılımcılar, etkinliklerini planlarken ve uygularken çocuk bilişi ve anlayışları, bilim okuryazarlığı, vatandaşlık-karakter eğitimi ve çocuk merkezli pedagojik stratejilere odaklanmışlardır. Katılımcıların çocukları değerlendirirken bireysel gözlemleri kullandıkları tespit edilmiştir. Sınırlı sayıda Montessori uygulayıcısı erken çocukluk dönemi eğitimcileriyle yürütülen bu çalışma, farklı programları uygulayan öğretmenlerin karşılaştırılacağı şekilde genişletilebilir.
Kimlik Gelişiminde Sosyal Bağlamın Rolü Üzerine Bir Gözden Geçirme Çalışması
Authors: Varol Didem
Published: September 2023

Kimlik gelişimi, tüm yaşam dönemleri boyunca çeşitli sosyal faktörler tarafından belirlenip şekillenmektedir. Kimlik gelişimini şekillendiren bu sosyal faktörler kendi içerisinde çok boyutlu bir yapı göstermektedir. Ekolojik Sistemler Teorisi bu yapıyı mikrosistem, mezosistem, egzosistem, makrosistem ve kronosistem olmak üzere beş alt sistemden oluşan bir model ile açıklamaktadır. Bu alt sistemlerden mikrosistem bireyin gelişim süreci boyunca doğrudan etkileşime geçtiği aile, okul ve akranlar gibi en temel sosyal grupları kapsamaktadır. Bu doğrultuda bu gözden geçirme çalışmasında kimlik gelişimi sürecinin sosyal bağlamını mikrosistem açısından incelemek; kimlik gelişimini aile, akranlar, yakın ilişkiler, okul ve öğretmenler açısından ele alan araştırmaların bulgularını derleyerek bu alanda çalışan araştırmacılara ve uygulama yapan uzmanlara öneriler sunmak amaçlanmıştır.
Türkiye’de TIMSS 2015 Uygulamasına Katılan 4. Sınıf Öğrencilerinin Fizik Başarısının Öğrenci ve Aile Özellikleri Açısından İncelenmesi
Authors: Yıldız Gamze , Taşlıdere Erdal
Published: September 2023

Bu çalışmada 2015 Uluslararası Matematik ve Fen Eğilimleri Araştırması (TIMSS 2015) uygulamasında ele alınan seçilmiş öğrenci ve aile faktörleri ile Türkiye’deki 4. sınıf öğrencilerinin fizik başarıları arasındaki ilişkisi incelenmiştir. Çalışma grubunu Türkiye’den TIMSS 2015 katılımcısı 6341 4. sınıf öğrencisi oluşturmaktadır. Fizik başarılarını etkileyen faktörler çok değişkenli regresyon analizinin hiyerarşik (blok girişi) metodu ile tespit edimiştir. Bu kapsamda bağımlı değişken öğrenci fizik başarısı; bağımsız değişkenler ise öğrenci ve aileye ait 21 değişkenden oluşmuştur. Analize ilk aşamada öğrenciye ait sekiz adet değişken girilmiştir. Söz konusu değişkenler TIMSS 2015 4. sınıf fizik başarısının %31,6’sını açıklamıştır. İkinci aşamada aileye ait 13 adet değişken ilave edilmiştir. İki aşamadan oluşan tüm model fizik başarısındaki toplam varyansın %49,3’ünü açıklamıştır. Elde edilen sonuçlar öğrenci faktörlerinden öğrencinin fen dersinde kendine güvenme düzeyi ile aile faktörlerinden, ebeveynin eğitim seviyesi değişkenlerinin fizik başarısına en fazla katkı sağlayan değişkenler olduğunu göstermiştir.
Analysis of Student Errors in Solving SPLDV Problems based on Newman's theory
Authors: Septia Tika , Nazilah Izzatun
Published: September 2023

The purpose of this study was to describe the types of errors made by Class VIII students when solving SPLDV questions based on Newman's theory. This qualitative research aims to provide descriptive information about individuals or observed behavior in the form of written or spoken words. Written tests and interviews were used to collect data. The test was carried out on all 25 Class VIII students, and then 3 of the 25 students were selected as research subjects. Data were analyzed by reducing information, presenting information, and drawing conclusions. The results of the work of individual testers were analyzed for the types of errors using the Newman analysis method. The factors that led to student errors were then explained in the interviews. Based on the study results, it can be concluded that the errors made by students in the SPLDV questions are as follows: 1) Failure to understand the problem, including not recording what is known and what is not in the duration of the task. Ask when in trouble. 2) Conversion errors, including misunderstanding of the billing method used. 3) Commanding process failure involves failing to continue to complete the process. 4) Error in writing HP, including not writing down HP. Student errors occur when students are not careful when solving problems, are too busy, or do not practice narrative tasks. 3) Commanding process failure involves failing to continue to complete the process. 4) Error in writing HP, including not writing down HP. Student errors occur when students are not careful when solving problems, are too busy, or do not practice narrative tasks. 3) Commanding process failure involves failing to continue to complete the process. 4) Error in writing HP, including not writing down HP. Student errors occur when students are not careful when solving problems, are too busy, or do not practice narrative tasks
PEMBUATAN WEBSITE DAN LOGO BISNIS SEBAGAI UPAYA MEMBANTU PEREKONOMIAN UMKM PADA MASA PANDEMI COVID-19 DI DESA TABA PASEMAH KECAMATAN TALANG EMPAT KABUPATEN BENGKULU TENGAH
Authors: Pratama Harizaldy Cahya
Published: September 2023

Pada masa pandemi Covid-19, usaha secara daring merupakan solusi yang telah dilakukan oleh banyak para pelaku UMKM, namun tidak semua pelaku UMKM dapat sukses malakukan usaha secara daring, dikarenakan usaha secara daring memerlukan kepercayaan yang kuat dari pelanggan, hal ini menyebabkan UMKM yang baru mulai, dapat kalah saing dengan usaha yang telah berjalan lama dan professional. Usaha secara online dapat terlihat professional jika usaha tersebut memiliki website yang dapat di percaya, dengan adanya website pemilik UMKM dapat meningkatkan kepercayaan pelanggan untuk membeli produknya dikarenakan website dapat mempromosikan produk yang di jual nya dengan cara memikat pelanggan dengan kalimat dan gambar yang di tampilkan pada website, sehingga pelanggan lebih percaya dengan toko yang menjual produk tersebut. Adapun tujuan dari program ini adalah untuk membantu UMKM yang terdampak pandemi dengan cara membuat website dan logo bisnis sehingga UMKM tampak professional di internet. Metode yang di gunakan adalah sasaran atau target pada program kerja individu KKN Mandiri, Observasi pada program kerja KKN Mandiri, dan kegiatan yang dilakukan selanjutnya adalah pembuatan website dan logo. Dengan metode ini akan menghasilkan website yang professional dan siap menarik pelanggan pada masa pandemi Covid-19.
The Effect of Digital Gaming Duration on Musculoskeletal System Symptoms: A Systematic Study
Authors: Sarıkaya Mehmet , Avcı Pelin , Satılmış Nuray , Kılınçarslan Gökmen , Bayraktar Işık , Bayrakdar Akan
Published: September 2023

The aim of this study is to review the existing literature on the musculoskeletal system symptoms associated with digital gaming. Literature related to the subject was searched in Web of Knowledge, PubMed, Medline, PsycINFO, Proquest, Google Scholar, and Sport Discuss databases. Articles published from 2010 to 2022 were scanned using keywords describing digital gaming-related postural disturbances, and musculoskeletal system exposure (pain, muscle activity). The articles were independently scanned by three authors, the relevant data were extracted, and the methodological quality of the included studies was evaluated. A total of 1252 articles were scanned for eligibility. Eleven articles are included in the study. Systematic reviews and meta-analysis studies were not included in our study. A wide range of prevalence rates of musculoskeletal complaints in different body regions has been reported, with the highest prevalence commonly found in neck complaints. This review has only found some evidence showing that a neck flexion posture as well as the frequency of digital gaming are associated with musculoskeletal disorders and pain, postural disorders among users of digital devices. The findings were presented and discussed in relation to the effects of digital games on posture and the musculoskeletal system. There is limited evidence that digital gaming and its various aspects (occupancy and properties) are associated with musculoskeletal system symptoms and exposures. Therefore, it is considered that evidence-based guidelines should be presented by experts for the wise use of digital games.
Preserve, Pressure, Protect, and Peel: The US-China Rivalry and the Politics of Vaccine Provision
Authors: Inouye Rikio
Published: September 2023

Lead states compete for influence, and the COVID-19 pandemic made clear the provision of vaccines, is a foreign policy tool. How and to which countries do providing states distribute aid amidst global a crises and great power rivalry? This article integrates both into a novel typology of strategies: preserving existing partnerships, pressuring opponents, protecting recipients based on need, and peeling off countries from geopolitical rivals. It analyzes US and Chinese COVID-19 vaccine distribution through 2021-2022. Regression results and Bayesian reasoning of original interviews suggest the US approach is characterized by protecting and peeling. China appears to be pressuring, preserving, and protecting. Case studies of Paraguay and Nicaragua – historic allies of Taiwan - further support these conclusions. This raises important questions regarding the circumstances under which aid provision is instrumental and how hegemonic rivals compete during global crises.
The Heisenberg Uncertainty Principle
Authors: LOH Kok Choy
Published: September 2023

The Heisenberg equation may not be as well-known as Einstein’s e=mc^2. But the Heisenberg equation’s implications that there is an irreducible uncertainty with regard to the position of an object are no less intriguing than the implications of Einstein’s relativity equation that time slows to a stop when the relative velocity of an object approaches the speed of light. Using elementary mathematics and science, this paper begins by examining the physics of motion of an everyday object such as a tennis ball. The paper shows that the same physics that applies to everyday objects in fact also applies when it comes to subatomic particles, such as an electron in motion. And by taking gradual incremental steps in developing the mathematics of the underlying physics, the paper leads to the conclusion that the universe is inherently uncertain, that it is impossible to know the exact position of any object.
The Nature of Matter
Authors: Sinha Arnab
Published: September 2023

In this paper, we reexamine the fundamental nature of mass and energy, contending that these traditionally regarded physical quantities are instead observed phenomena, continually emerging, and vanishing in cyclic patterns intricately interwoven with the essence of time. We uncover that the cyclical behaviour of mass and energy leads to the quantization of energy and the wave-particle duality, defining phenomena in the quantum realm. Intriguingly, these cycles also unveil the concept of 'Dark Matter,' manifesting as mass absence during specific phases. Furthermore, we present an illuminating perspective on energy transformations, unifying gravity and electromagnetism. Our exploration not only challenges existing paradigms but also delves into the philosophical distinction between the ephemeral nature of mass and energy and the enduring act of observation, redefining our comprehension of the universe's intricate fabric.
Presentación
Authors: Díaz Rosales Raúl
Published: September 2023

Presentación de resumen
Effect of low-dose blanched Saccharina latissima in finishing bulls’ diets on carcass and meat quality traits
Authors: Grabež Vladana , Mydland Liv Torunn , Papoutsis Dimitrios , Øverland Margareth , Egelandsdal Bjørg
Published: September 2023

Nutritional and bioactive compounds present in seaweeds make them suitable supplements or feed ingredients in livestock diets. This study assessed the effect of blanched seaweed (Saccharina latissima) as a supplement in finishing bulls’ diets on carcass traits and the quality of the longissimus lumborum (LL) and semimembranosus (SM) muscles. A concentration of 0.8% dry matter of blanched S. latissima in bulls’ diets was the maximum amount allowed, owing to iodine and arsenic thresholds in animal feed. Nineteen Limousin crossbreed bulls were randomly assigned to two groups, fed a control (CD, n = 9) diet or a test diet supplemented with blanched seaweed (SW, n = 10), and fed for 48 days pre slaughter. The carcasses from the bulls finished on a seaweed-supplemented diet were heavier (p < 0.05) than those in the control group, while levels of conformation and fatness were similar between the groups (p > 0.05). The pH was lower (p < 0.05) in the LL of CD-fed animals in early post mortem than in the LL of SW-fed animals, whereas no differences (p > 0.05) were found in the ultimate pH. The meat from the bulls fed both diets had a similar (p > 0.05) drip loss and shear force at days 7 and 14. The cooking loss at day 7 was not affected (p > 0.05) by diet, whereas on day 14 the cooking loss was greater (p < 0.05) for SW than for CD meat. Warmed-over flavor and shear force were muscle dependent and lower (p < 0.05) for LL than SM. Seaweed supplementation in finishing bulls’ diets had no clear effect on color changes (L*, a*, and b* values) during chilled storage, although reduced b* values (p < 0.05) suggest an improved color stability of meat from SW- compared with CD-fed animals. The iodine content was higher (p < 0.05) in the SW meat than in the CD meat, even when using the low seaweed supplementation level requested by the authorities. A small increase of arsenic in the meat with seaweed supplementation has no implications on human health. Cost-efficient processing methods for the further reduction of iodine and arsenic are needed to increase the utilization of seaweed as a feed additive/ingredient and attain a clear effect on meat quality.
Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7
Authors: Okada Yasunobu , Numata Tomohiro , Sabirov Ravshan Z. , Kashio Makiko , Merzlyak Peter G. , Sato-Numata Kaori
Published: September 2023

Cell volume regulation (CVR) is a prerequisite for animal cells to survive and fulfill their functions. CVR dysfunction is essentially involved in the induction of cell death. In fact, sustained normotonic cell swelling and shrinkage are associated with necrosis and apoptosis, and thus called the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. Since a number of ubiquitously expressed ion channels are involved in the CVR processes, these volume-regulatory ion channels are also implicated in the NVI and AVD events. In Part 1 and Part 2 of this series of review articles, we described the roles of swelling-activated anion channels called VSOR or VRAC and acid-activated anion channels called ASOR or PAC in CVR and cell death processes. Here, Part 3 focuses on therein roles of Ca2+-permeable non-selective TRPM2 and TRPM7 cation channels activated by stress. First, we summarize their phenotypic properties and molecular structure. Second, we describe their roles in CVR. Since cell death induction is tightly coupled to dysfunction of CVR, third, we focus on their participation in the induction of or protection against cell death under oxidative, acidotoxic, excitotoxic, and ischemic conditions. In this regard, we pay attention to the sensitivity of TRPM2 and TRPM7 to a variety of stress as well as to their capability to physicall and functionally interact with other volume-related channels and membrane enzymes. Also, we summarize a large number of reports hitherto published in which TRPM2 and TRPM7 channels are shown to be involved in cell death associated with a variety of diseases or disorders, in some cases as double-edged swords. Lastly, we attempt to describe how TRPM2 and TRPM7 are organized in the ionic mechanisms leading to cell death induction and protection.
ICOSLG-associated immunological landscape and diagnostic value in oral squamous cell carcinoma: a prospective cohort study
Authors: Dong Yuexin , Hu Xinyang , Xie Shixin , Song Yuxian , He Yijia , Jin Wanyong , Ni Yanhong , Wang Zhiyong , Ding Liang
Published: September 2023

Background: We previously reported that stroma cells regulate constitutive and inductive PD-L1 (B7-H1) expression and immune escape of oral squamous cell carcinoma. ICOSLG (B7-H2), belongs to the B7 protein family, also participates in regulating T cells activation for tissue homeostasis via binding to ICOS and inducing ICOS+ T cell differentiation as well as stimulate B-cell activation, while it appears to be abnormally expressed during carcinogenesis. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for the maximum response rate of ICOSLG-based immunotherapy in a specific population.

Methods: This retrospective study included OSCC tissue samples (n = 105) to analyze the spatial distribution of ICOSLG. Preoperative peripheral blood samples (n = 104) and independent tissue samples (n = 10) of OSCC were collected to analyze the changes of immunocytes (T cells, B cells, NK cells and macrophages) according to ICOSLG level in different cellular contents.

Results: ICOSLG is ubiquitous in tumor cells (TCs), cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TILs). Patients with high ICOSLGTCs or TILs showed high TNM stage and lymph node metastasis, which predicted a decreased overall or metastasis-free survival. This sub-cohort was featured with diminished CD4+ T cells and increased Foxp3+ cells in invasive Frontier in situ, and increased absolute numbers of CD3+CD4+ and CD8+ T cells in peripheral blood. ICOSLG also positively correlated with other immune checkpoint molecules (PD-L1, CSF1R, CTLA4, IDO1, IL10, PD1).

Conclusion: Tumor cell-derived ICOSLG could be an efficient marker of OSCC patient stratification for precision immunotherapy.
Mutations in genes related to myocyte contraction and ventricular septum development in non-syndromic tetralogy of Fallot
Authors: Harvey Drayton C. , Verma Riya , Sedaghat Brandon , Hjelm Brooke E. , Morton Sarah U. , Seidman Jon G. , Kumar S. Ram
Published: September 2023

Objective

Eighty percent of patients with a diagnosis of tetralogy of Fallot (TOF) do not have a known genetic etiology or syndrome. We sought to identify key molecular pathways and biological processes that are enriched in non-syndromic TOF, the most common form of cyanotic congenital heart disease, rather than single driver genes to elucidate the pathogenesis of this disease.

Methods

We undertook exome sequencing of 362 probands with non-syndromic TOF and their parents within the Pediatric Cardiac Genomics Consortium (PCGC). We identified rare (minor allele frequency <1 × 10−4), de novo variants to ascertain pathways and processes affected in this population to better understand TOF pathogenesis. Pathways and biological processes enriched in the PCGC TOF cohort were compared to 317 controls without heart defects (and their parents) from the Simons Foundation Autism Research Initiative (SFARI).

Results

A total of 120 variants in 117 genes were identified as most likely to be deleterious, with CHD7, CLUH, UNC13C, and WASHC5 identified in two probands each. Gene ontology analyses of these variants using multiple bioinformatic tools demonstrated significant enrichment in processes including cell cycle progression, chromatin remodeling, myocyte contraction and calcium transport, and development of the ventricular septum and ventricle. There was also a significant enrichment of target genes of SOX9, which is critical in second heart field development and whose loss results in membranous ventricular septal defects related to disruption of the proximal outlet septum. None of these processes was significantly enriched in the SFARI control cohort.

Conclusion

Innate molecular defects in cardiac progenitor cells and genes related to their viability and contractile function appear central to non-syndromic TOF pathogenesis. Future research utilizing our results is likely to have significant implications in stratification of TOF patients and delivery of personalized clinical care.
Effect of physical activity and different exercise modalities on glycemic control in people with prediabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Bennasar-Veny Miquel , Malih Narges , Galmes-Panades Aina M. , Hernandez-Bermudez Ivonne C. , Garcia-Coll Natalia , Ricci-Cabello Ignacio , Yañez Aina M.
Published: September 2023

Background

Numerous studies have shown the beneficial effects of exercise on glycemic control in people with prediabetes. However, the most effective exercise modality for improving glycemic control remains unclear. We aimed to assess which exercise training modality is most effective in improving glycemic control in a population with prediabetes.

Methods

We conducted searches in Pubmed/MEDLINE, EMBASE, SPORTDiscus, Web of Science, PEDro, BVS, and the Cochrane Library from inception to June 2022. Included studies reported fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and 2-hour postprandial (2hPP) levels and implemented an exercise program lasting at least 12 weeks in adults with prediabetes. We performed a direct meta-analysis using a random-effects model and a network meta-analysis. Cochran’s Q statistic and the inconsistency I2 test were used to assess the heterogenicity between studies.

Results

Twenty trials were included, with 15 trials (comprising 775 participants with prediabetes) combined in the meta-analysis, and 13 in the network meta-analysis. The meta-analysis results did not show a statistically significant reduction in fasting plasma glucose (FPG) after aerobic training (AT) intervention compared to a control group (mean (95%CI) difference = -5.18 (-13.48; 3.12) mg/dL, Z=1.22, p=0.22). However, a difference of -7.25 (-13.79; -0.71) mg/dL, p=0.03, in FPG after interval training (IT) intervention was detected compared to a control group. After resistance training (RT) intervention, FPG was significantly lower -6.71 (-12.65,-0.77) mg/dL, Z=2.21, p=0.03, and HbA1c by -0.13 (-0.55, 0.29), p=0.54, compared to the control group. The impact of RT compared to no intervention on 2hPP was not statistically significant (p=0.26). The network meta-analysis did not show statistical significance. Most of the studies presented an unclear risk of bias, and a low and very low-quality of evidence. According to the GRADE criteria, the strength of the body of evidence was low.

Conclusion

Resistance training and IT had demonstrated benefits on glycemic indices, especially on FPG, in a population with prediabetes. Further studies with larger sample sizes and a more robust methodology that compare different types of exercise modalities, frequencies, and durations, are needed to establish a beneficial exercise intervention.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370688, identifier CRD42022370688.
Isolating the effects of land use and functional variation on Yucatán's forest biomass under global change
Authors: George-Chacon Stephanie P. , Smallman T. Luke , Dupuy Juan Manuel , Hernández-Stefanoni José Luis , Milodowski David T. , Williams Mathew
Published: September 2023

Tropical forests hold large stocks of carbon in biomass and face pressures from changing climate and anthropogenic disturbance. Forests' capacity to store biomass under future conditions and accumulate biomass during regrowth after clearance are major knowledge gaps. Here we use chronosequence data, satellite observations and a C-cycle model to diagnose woody C dynamics in two dry forest ecotypes (semi-deciduous and semi-evergreen) in Yucatán, Mexico. Woody biomass differences between mature semi-deciduous (90 MgC ha−1) and semi-evergreen (175 MgC ha−1) forest landscapes are mostly explained by differences in climate (c. 60%), particularly temperature, humidity and soil moisture effects on production. Functional variation in foliar phenology, woody allocation, and wood turnover rate explained c. 40% of biomass differences between ecotypes. Modeling experiments explored varied forest clearance and regrowth cycles, under a range of climate and CO2 change scenarios to 2100. Production and steady state biomass in both ecotypes were reduced by forecast warming and drying (mean biomass 2021–2100 reduced 16–19% compared to 2001–2020), but compensated by fertilisation from rising CO2. Functional analysis indicates that trait adjustments amplify biomass losses by 70%. Experiments with disturbance and recovery across historically reported levels indicate reductions to mean forest biomass stocks over 2021–2100 similar in magnitude to climate impacts (10–19% reductions for disturbance with recovery). Forest disturbance without regrowth amplifies biomass loss by three- or four-fold. We conclude that vegetation functional differences across the Yucatán climate gradient have developed to limit climate risks. Climate change will therefore lead to functional adjustments for all forest types. These adjustments are likely to magnify biomass reductions caused directly by climate change over the coming century. However, the range of impacts of land use and land use change are as, or more, substantive than the totality of direct and indirect climate impacts. Thus the carbon storage of Yucatan's forests is highly vulnerable both to climate and land use and land use change. Our results here should be used to test and enhance land surface models use for dry forest carbon cycle assessment regionally and globally. A single plant functional type approach for modeling Yucatán's forests is not justified.
Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review
Authors: Li Honglin , Zhang Lei , Yang Feiran , Zhao Ruohan , Li Xiurong , Li Huijie
Published: September 2023

Introduction

Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.

Methods

We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.

Results

We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.

Conclusion

Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.
The clinical relevance of OSM in inflammatory diseases: a comprehensive review
Authors: Wolf Cody L. , Pruett Clyde , Lighter Darren , Jorcyk Cheryl L.
Published: September 2023

Oncostatin M (OSM) is a pleiotropic cytokine involved in a variety of inflammatory responses such as wound healing, liver regeneration, and bone remodeling. As a member of the interleukin-6 (IL-6) family of cytokines, OSM binds the shared receptor gp130, recruits either OSMRβ or LIFRβ, and activates a variety of signaling pathways including the JAK/STAT, MAPK, JNK, and PI3K/AKT pathways. Since its discovery in 1986, OSM has been identified as a significant contributor to a multitude of inflammatory diseases, including arthritis, inflammatory bowel disease, lung and skin disease, cardiovascular disease, and most recently, COVID-19. Additionally, OSM has also been extensively studied in the context of several cancer types including breast, cervical, ovarian, testicular, colon and gastrointestinal, brain,lung, skin, as well as other cancers. While OSM has been recognized as a significant contributor for each of these diseases, and studies have shown OSM inhibition is effective at treating or reducing symptoms, very few therapeutics have succeeded into clinical trials, and none have yet been approved by the FDA for treatment. In this review, we outline the role OSM plays in a variety of inflammatory diseases, including cancer, and outline the previous and current strategies for developing an inhibitor for OSM signaling.
Immunonutrition: facilitating mucosal immune response in teleost intestine with amino acids through oxidant-antioxidant balance
Authors: Hissen Karina L. , He Wenliang , Wu Guoyao , Criscitiello Michael F.
Published: September 2023

Comparative animal models generate fundamental scientific knowledge of immune responses. However, these studies typically are conducted in mammals because of their biochemical and physiological similarity to humans. Presently, there has been an interest in using teleost fish models to study intestinal immunology, particularly intestinal mucosa immune response. Instead of targeting the pathogen itself, a preferred approach for managing fish health is through nutrient supplementation, as it is noninvasive and less labor intensive than vaccine administrations while still modulating immune properties. Amino acids (AAs) regulate metabolic processes, oxidant-antioxidant balance, and physiological requirements to improve immune response. Thus, nutritionists can develop sustainable aquafeeds through AA supplementation to promote specific immune responses, including the intestinal mucosa immune system. We propose the use of dietary supplementation with functional AAs to improve immune response by discussing teleost fish immunology within the intestine and explore how oxidative burst is used as an immune defense mechanism. We evaluate immune components and immune responses in the intestine that use oxidant-antioxidant balance through potential selection of AAs and their metabolites to improve mucosal immune capacity and gut integrity. AAs are effective modulators of teleost gut immunity through oxidant-antioxidant balance. To incorporate nutrition as an immunoregulatory means in teleost, we must obtain more tools including genomic, proteomic, nutrition, immunology, and macrobiotic and metabonomic analyses, so that future studies can provide a more holistic understanding of the mucosal immune system in fish.
Immune checkpoint inhibitors-related pancreatitis with fulminant type 1 diabetes mellitus: case report and literature review
Authors: Fang Wei , Gao Yang , Shi Xiaoyan , Zhang Xiaoran , Zhou Shan , Zhu Hongxia , Yan Wei , Wang Huanping
Published: September 2023

Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced human malignancies. ICIs-related adverse events, including pancreatitis and diabetes, have been individually characterized in the literature. The co-occurrence of ICIs-related pancreatitis with diabetes is rare and easily overlooked, but it is often severe or fatal. We present a patient with renal tumor resection who was treated with injection of the PD-L1 inhibitor toripalimab and eventually developed acute pancreatitis and fulminant type 1 diabetes mellitus. In addition, we conducted a literature review of ICIs-related pancreatitis with diabetes. The case in our report presented with paroxysmal abdominal pain and loss of appetite. Intravenous fluids and insulin infusion improved the patient’s pancreatitis and explosive hyperglycemia. This article suggests that ICIs can affect endocrine and exocrine functions of the pancreas, while providing information and new perspectives for the diagnosis and treatment of this challenging rare disease, helping inspire clinicians for the early identification and effective management of similar cases.
Morbidity and mortality related to type II odontoid fractures in octogenarians undergoing surgery: a retrospective study with 5 year follow up
Authors: Lenga Pavlina , Gülec Gelo , Kiening Karl , Unterberg Andreas W. , Ishak Basem
Published: September 2023

Introduction

The prevalence of trauma is increasing in the geriatric population. The optimal therapy for type II odontoid fractures in the elderly is controversial. This study aims to assess the morbidity and mortality associated with odontoid fractures in octogenarians undergoing C1/C2 posterior screw fixation and describe the perioperative and post-operative complications and risk factors associated with mortality.

Materials and methods

Electronic medical records from a single institution pertaining to the period between September 2005 and December 2020 were retrieved. Data on patient demographics, neurological conditions, surgical characteristics, complications, hospital course, and 90-day mortality were collected.

Results

Over a 16-year period, 60 patients aged ≥80 years diagnosed with type II odontoid fractures were enrolled in the study. The mean age was 85.0 ± 1.9 years. The mean Charlson Comorbidity Index (CCI) was >6 indicating a poor baseline reserve (8.5 ± 1.9), while cardiovascular diseases were the most prevalent among comorbidities. The mean surgical duration was 217.5 ± 65.9 min, with a mean blood loss of 725.5 ± 275.7 mL. The in-hospital was 5–0% and the 90-day mortality rates increased at 10.0%. No revision surgery was needed in any of the cases. Intraoperative and post-operative X-ray and computed tomography (CT) imaging revealed correct screw placement. Proper alignment of the atlantoaxial spine and fusion could be achieved in all cases. The unique risk factors for mortality included the presence of comorbidities and the occurrence of post-operative complications.

Conclusion

The complication and mortality rates associated with odontoid fractures in octogenarians are relatively high. However, the therapeutic goals in this population also include bone union and preservation of neurological status. Despite the often-high comorbidity rate, we still recommend that surgery should be considered in patients over 80 years. However, it is necessary to evaluate several approaches when treating such frail patients.
Purification of linearized template plasmid DNA decreases double-stranded RNA formation during IVT reaction
Authors: Martínez Juan , Lampaya Verónica , Larraga Ana , Magallón Héctor , Casabona Diego
Published: September 2023

After the COVID-19 pandemic, messenger RNA (mRNA) has revolutionized traditional vaccine manufacturing. With the increasing number of RNA-based therapeutics, valuable new scientific insights into these molecules have emerged. One fascinating area of study is the formation of double-stranded RNA (dsRNA) during in vitro transcription (IVT) which is considered a significant impurity, as it has been identified as a major trigger in the cellular immune response pathway. Therefore, there is a growing importance placed to develop and optimize purification processes for the removal of this by-product. Traditionally, efforts have primarily focused on mRNA purification after IVT through chromatographic separations, with anion exchange and reverse phase chromatography emerging as effective tools for this purpose. However, to the best of our knowledge, the influence and significance of the quality of the linearized plasmid have not been thoroughly investigated. Plasmids production involves the growth of bacterial cultures, bacterial harvesting and lysis, and multiple filtration steps for plasmid DNA purification. The inherent complexity of these molecules, along with the multitude of purification steps involved in their processing, including the subsequent linearization and the less-developed purification techniques for linearized plasmids, often result in inconsistent batches with limited control over by-products such as dsRNA. This study aims to demonstrate how the purification process employed for linearized plasmids can impact the formation of dsRNA. Several techniques for the purification of linearized plasmids based on both, resin filtration and chromatographic separations, have been studied. As a result of that, we have optimized a chromatographic method for purifying linearized plasmids using monolithic columns with C4 chemistry (butyl chains located in the surface of the particles), which has proven successful for mRNAs of various sizes. This chromatographic separation facilitates the generation of homogeneous linearized plasmids, leading to mRNA batches with lower levels of dsRNA during subsequent IVT processes. This finding reveals that dsRNA formation is influenced not only by RNA polymerase and IVT conditions but also by the quality of the linearized template. The results suggest that plasmid impurities may contribute to the production of dsRNA by providing additional templates that can be transcribed into sequences that anneal with the mRNA molecules. This highlights the importance of considering the quality of plasmid purification in relation to dsRNA generation during transcription. Further investigation is needed to fully understand the mechanisms and implications of plasmid-derived dsRNA. This discovery could shift the focus in mRNA vaccine production, placing more emphasis on the purification of linearized plasmids and potentially saving, in some instances, a purification step for mRNA following IVT.
Mild hypoxia-induced structural and functional changes of the hippocampal network
Authors: Hencz Alexandra , Magony Andor , Thomas Chloe , Kovacs Krisztina , Szilagyi Gabor , Pal Jozsef , Sik Attila
Published: September 2023

Hypoxia causes structural and functional changes in several brain regions, including the oxygen-concentration-sensitive hippocampus. We investigated the consequences of mild short-term hypoxia on rat hippocampus in vivo. The hypoxic group was treated with 16% O2 for 1 h, and the control group with 21% O2. Using a combination of Gallyas silver impregnation histochemistry revealing damaged neurons and interneuron-specific immunohistochemistry, we found that somatostatin-expressing inhibitory neurons in the hilus were injured. We used 32-channel silicon probe arrays to record network oscillations and unit activity from the hippocampal layers under anaesthesia. There were no changes in the frequency power of slow, theta, beta, or gamma bands, but we found a significant increase in the frequency of slow oscillation (2.1–2.2 Hz) at 16% O2 compared to 21% O2. In the hilus region, the firing frequency of unidentified interneurons decreased. In the CA3 region, the firing frequency of some unidentified interneurons decreased while the activity of other interneurons increased. The activity of pyramidal cells increased both in the CA1 and CA3 regions. In addition, the regularity of CA1, CA3 pyramidal cells’ and CA3 type II and hilar interneuron activity has significantly changed in hypoxic conditions. In summary, a low O2 environment caused profound changes in the state of hippocampal excitatory and inhibitory neurons and network activity, indicating potential changes in information processing caused by mild short-term hypoxia.
Diagnosing multiple system atrophy: current clinical guidance and emerging molecular biomarkers
Authors: Goolla Meghana , Cheshire William P. , Ross Owen A. , Kondru Naveen
Published: September 2023

Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder characterized by motor and autonomic dysfunction. Accurate and early diagnosis of MSA is challenging due to its clinical similarity with other neurodegenerative disorders, such as Parkinson’s disease and atypical parkinsonian disorders. Currently, MSA diagnosis is based on clinical criteria drawing from the patient’s symptoms, lack of response to levodopa therapy, neuroimaging studies, and exclusion of other diseases. However, these methods have limitations in sensitivity and specificity. Recent advances in molecular biomarker research, such as α-synuclein protein amplification assays (RT-QuIC) and other biomarkers in cerebrospinal fluid and blood, have shown promise in improving the diagnosis of MSA. Additionally, these biomarkers could also serve as targets for developing disease-modifying therapies and monitoring treatment response. In this review, we provide an overview of the clinical syndrome of MSA and discuss the current diagnostic criteria, limitations of current diagnostic methods, and emerging molecular biomarkers that offer hope for improving the accuracy and early detection of MSA.
Inonotus obliquus polysaccharide are linear molecules that alter the abundance and composition of intestinal microbiota in Sprague Dawley rats
Authors: Liu Songqing , Zhou Wenjing , Deng Xin , Jiang Wei , Wang Yanping , Zhan Jiasui , Hu Binhong
Published: September 2023

Introduction

The macromolecular polysaccharide Inonotus obliquus polysaccharide (IOP) is composed of various monosaccharides, and it could modulate the composition and diversity of intestinal flora. However, its impact on the intestinal flora in rats of different genders remains unclear. Therefore, this study aims to investigate the structural changes of IOP and its effects on the intestinal flora after administration in male and female rats.

Methods

In this study, the molecular weight and purity of IOP were analyzed by high-performance gel permeation chromatography (HPGPC) and phenol sulfuric acid method, and NMR was used to confirm the chemical structure of IOP. Sex hormone [testosterone (T) and estradiol (E2)] levels and intestinal microbial changes were detected by enzyme-linked immunosorbent assay (ELISA) and 16S rRNA, respectively, after gavage of IOP (100 mg/kg) in male and female Sprague Dawley (SD) rats.

Results

HPGPC analysis showed that the average molecular weight (Mw) of IOP was 4,828  Da, and the total sugar content of the purified IOP was 96.2%, indicating that the polysaccharide is of high purity. NMR revealed that IOP is a linear macromolecule with an α-D-type glucose backbone. The results of ELISA and 16S rRNA showed that the IOP increased the abundance of beneficial bacteria, such as Clostridia_UCG-014 and Prevotellaceae_NK3B31, and reduced that of harmful bacteria, such as Colidextribacter and Desulfobacterota in the intestine of both male and female rats, and IOP changed the levels of sex hormones in male and female rats. Further analyses revealed that the increase in alpha diversity was higher in male than female rats. α diversity and β diversity revealed a significant difference in the composition of cecal microbiota between male and female rats in the control group, but IOP intake reduced this difference. Meanwhile, α analysis revealed a change in the composition of bacterial flora was more stable in male than female rats.

Conclusions

This study enhances our comprehension of the IOP structure and elucidates the alterations in intestinal flora following IOP administration in rats of varying genders. Nonetheless, further investigation is warranted to explore the specific underlying reasons for these discrepancies.