bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of TikTok as Japanese Learning Media
Authors: Fitrianingsih Fitrianingsih , Nurjaleka Lisda
Published: October 2023

In this technological era, social media has an important role in all fields. Various types of social media are used by the public, one of which is TikTok. TikTok's diverse video content provides benefits for its users. One type of video content that can be found on TikTok is learning video content that can be used as an alternative learning resource or learning media. One of the many learning video content found on TikTok is language learning video content. For example, Japanese language learning video content. The learning video content needs to be sorted first so that its use can be maximized. For this reason, this study aims to determine the type of learning and the level of Japanese language profiency contained in the Japanese language learning video content on TikTok. The method used in this study is a qualitative descriptive method which is providing detailed and factual data interpretation. Based on the research, there are 7 types of Japanese language learning (Aisatsu, Bunka, Bunpou, Goi, Kaiwa, Linguistics, and Moji) that can be found on TikTok video content. Meanwhile, the level of Japanese language proficiency that be found is level A1 to level B2 and level N5 to level N1.
Diabetic retinopathy in the practice of an optometrist
Authors: Sotnikova Yu. P. , Loskutov I. A. , Sotnikov D. S. , Piryatinsky B.
Published: October 2023

Diabetic retinopathy is a microangiopathy that occurs as a result of chronic prolonged exposure to high glucose levels on the retina of the eyes. In optometric practice, a specialist, on the one hand, faces the impossibility of performing a complete correction of vision, and on the other, may be the first to suspect such a pathology and refer the patient to a doctor. At the same time, it should be noted that medical professionals specializing in the treatment of diabetes often work in isolation, which requires patients to visit several clinics and specialists. Despite the great relevance, in many countries, difficulties remain in coordinating treatment programs for narrow-profile specialists who provide assistance to people living with diabetes. In this article we discuss the epidemiology, describe an approach to its assessment, diagnosis and provide an overview of the principles of treatment of diabetic retinopathy. In this article we discuss the epidemiology and natural history of diabetic retinopathy and describe an approach to its assessment, diagnosis and provide an overview of the principles of treatment of diabetic retinopathy. The article mentions a large number of people with diabetic retinopathy in the world, including in Russia, and notes that the actual prevalence is probably higher than the reported figures.
Pengaruh Pelarut Etanol 70% Dan Metanol Terhadap Kadar Flavonoid Total Ekstrak Daun Sirsak (Annona muricata Linn)
Authors: Putri Juliance Yolanda , Nastiti Kunti , Hidayah Nurul
Published: October 2023

Latar Belakang: Daun Sirsak (Annona muricata Linn) secara empiris digunakan untuk mengobati berbagai macam penyakit. Salah satu potensi daun ini sebagai antioksidan karna mengandung senyawa flavonoid. Penelitian menggunakan pelarut yang bersifat polar yakni etanol 70% dan metanol untuk mengekstraksi senyawa flavonoid pada daun sirsak, penggunaan jenis pelarut berbeda akan mempengaruhi kadar flavonoid total yang dihasilkan.

Tujuan: Mengetahui pengaruh perbedaan jenis pelarut etanol 70% dan metanol terhadap kadar flavonoid total daun sirsak serta deteksi kualitatif senyawa flavonoid.

Metode: Penelitian menggunakan metode pre eksperimental, pembuatan ekstrak daun sirsak menggunakan metode maserasi dengan membandingkan pelarut etanol 70% dan metanol selanjutnya senyawa flavonoid dideteksi secara kualitatif menggunakan pereaksi warna dan kromotografi lapis tipis, kemudian penentuan kadar flavonoid dengan Spektrofotometri UV-Vis dan data dianalisa dengan uji One Way Anova.

Hasil: Hasil uji deteksi kualitatif senyawa flavonoid daun sirsak menunjukkan hasil positif dan kadar flavonoid total yang dihasilkan oleh ekstrak etanol 70% dan metanol daun sirsak adalah 6,79 mg QE/g dan 9,25 mg QE/g. Hasil analisa uji One Way Anova menunjukkan perbedaan jenis pelarut berpengaruh signifikan terhadap kadar flavonoid total ekstrak daun sirsak.

Kesimpulan: Perbedaan jenis pelarut berpengaruh signifikan terhadap kadar flavonoid total ekstrak daun sirsak dengan kadar tertinggi dihasilkan pelarut metanol sebesar 9,25 mg QE/g.
Uji Aktivitas Antibakteri Fraksi N-Heksan Kayu Bajakah (Uncaria tomentosa) Terhadap Bakteri Escherichia coli
Authors: Nirmalasari Firda , Nastiti Kunti , Audina Mia
Published: October 2023

Latar Belakang: Penyakit diare merupakan penyakit infeksi yang masih menjadi kasus tertinggi di Indonesia. Terapi obat yang saat ini digunakan sebagai drug of choice pada penyakit diare yaitu antibiotik golongan kloramfenikol. Dapat diketahui bahwa pengobatan menggunakan bahan kimia lebih rentan  menimbulkan efek samping yang tidak diinginkan. Untuk menghadapi masalah ini perlu dilakukan upaya berupa eksplorasi terapi terbaru untuk membunuh bakteri. Sumber terapi terbaru yang dapat ditemukan dari tanaman-tanaman yang berpotensi sebagai antibakteri.

Tujuan: Penelitian ini bertujuan untuk mengetahui aktivitas antibakteri fraksi n-heksan pada ekstrak kayu bajakah (Uncaria tomentosa) dengan menguji daya hambat dan daya bunuh dengan melihat hambat minimum dan bunuh minimum pada bakteri Escherichia coli.

Metode: Penelitian ini menggunakan jenis penelitian true experimental dalam pembuatan ekstrak menggunakan metode maserasi dan metode uji aktivitas antibakteri digunakan metode difusi cakram dan dilanjutkan dengan metode dilusi dengan konsentrasi 100,50,25,12,5, dan 6,25 ppm dan ditentukan konsentrasi hambat minimum dan konsentrasi bunuh minimum. Analisis data ini menggunakan uji Kruskal-Wallis dan Mann Whitney.

Hasil: Hasil aktivitas antibakteri fraksi n-heksan kayu bajakah (Uncaria tomentosa) terhadap bakteri Escherichia coli dengan zona hambat sebesar 7,72 mm. Hasil analisis menunjukan terdapat perbedaan bermakna dengan p value 0,005 pada Kruskal-Wallis dan pada Mann Whitney menunjukan p value 0,05. konsentrasi hambat minimum (KHM) menunjukkan kejernihan di konsentrasi 50 ppm.

Simpulan: Fraksi n-heksan kayu bajakah terhadap bakteri Escherichia coli memiliki nilai konsentrasi hambat minimum (KHM) di konsentarsi 50 ppm. Namun, tidak memiliki nilai konsentrasi bunuh minimum (KBM).
Penurunan Kadar Logam Timbal (Pb) pada Ikan Baung dengan Filtrat Jeruk Purut (Citrus hystrix)
Authors: Hasanah Huswatun , Rahmadani Rahmadani , Hidayah Nur
Published: October 2023

Latar Belakang: Ikan Baung adalah ikan yang banyak hidup diperairan tawar yang memiliki nutrisi dan protein. Ikan Baung merupakan ikan demersal yaitu suka mencari makan di dasar perairan yang mungkin terkontaminasi oleh logam berat seperti timbal yang mengendap di dasar perairan. Timbal merupakan suatu zat yang dapat mencemari perairan dan ditemukan sebagai cemaran yang diakibatkan karena tongkang batu bara di wilayah Sungai Kahayan.

Tujuan: Untuk mengetahui Penuranan kadar logam timbal (Pb) pada Ikan Baung menggunakan Filtrat Jeruk Purut

Metode: Penelitian ini menggunakan True Experimental dengan Post Test Only Control Group Design. Metode uji yang dilakukan secara kuantitatif. Metode pengujian kuantitatif menggunakan Spektrofotometri Serap Atom dengan panjang gelombang 283 nm. Analisis data yang digunakan ANOVA ONE-WAY.

Hasil: Hasil yang didapatkan berdasarkan analisis kuantitatif diperoleh data yang kurang segnifikan menggunakan filtrat jeruk purut 75% dengan interval waktu 30 menit, 60 menit dan 90 menit dengan total penurunan pada ikan 1 pada menit ke 30 sebesar 0,183 pada menit 60 sebesar 0,086 dan pada menit ke 90 sebesar 0,113. Pada ikan 2 menit ke 30 mengalami penurunan sebesar 0,125 pada menit ke 60 sebesar 094 dan pada menit ke 90 sebesar 0,365. Pada ikan ke 3 menit ke 30 mengalami penurunan sebesar 0,338 pada menit ke 60 sebesar 0,080 dan pada menit ke 90 sebesar 0,083.

Simpulan: Pemberian filtrat jeruk purut dengan konsentrasi 75% dengan interval waktu yang berbeda (30 menit, 60 menit, 90 menit) menunjukan bahwa tidak ada pengaruh yang signifikan terhadap penurunanan kadar logam timbal (Pb) menggunakan interval waktu perendaman.
Hubungan Tingkat Pengetahuan Dengan Kepatuhan Minum Obat Antihipertensi Pada Pasien Program Rujuk Balik (PRB) Di Puskesmas Kayu Tangi
Authors: Fajriati Nur , Kurniawati Darini , Aditya Rahman R. Topan
Published: October 2023

Latar belakang: Hipertensi secara luas dikenal sebagai penyakit kardiovaskuler, dimana penderita memiliki tekanan darah diatas normal yakni tekanan darah sistolik â‰¥140mmHg dan tekanan darah diastolik â‰¥90 mmHg. Kepatuhan minum obat pada penderita hipertensi sangatlah penting karena dapat mengontrol tekanan darahpada penderita hipertensi sehingga dapat mencegah terjadinya komplikasi. Tingkat pengetahuan pasien hipertensi terkait penyakitnya dapat menunjang keberhasilan terapi sehingga tekanan darah pasien hipertensi dapat terkontrol dengan baik. Tujuan: Mengetahui hubungan tingkat pengetahuan dengankepatuhan minum obat antihipertensi pada pasien PRB di Puskesmas Kayu Tangi. Metode: Penelitian ini menggunakan observasional analitik dengan pendekatan Cross Sectional, pengumpulan data dilakukan secara prospektif menggunakan kuesioner pengetahuan yang telah diuji validitas dan reliabilitas dan kuesioner kepatuhan menggunakan Morisky Medication Adherence Scale (MMAS-8). Hasil: Penelitian ini mendapatkan hasil uji statistik koefisien kontingensi dengan diperoleh nilai p = 0,000 < Î± 0,05 yang artinya Ho ditolak dan Ha diterima.Kesimpulan: Ada hubungan antara tingkat pengetahuan dan kepatuhan minum obat antihipertensi pada pasien PRB di Puskesmas Kayu Tangi
Masculinity and veganism: the effect of linking vegan dishes with masculinity on men's attitudes toward vegan food
Authors: Scholz Alma Elisabeth , Lenhart Jan
Published: October 2023

Introduction

Vegetarian or vegan diets are not yet popular with most men, though they are beneficial for both health and the environment. Men's low preference for such diets might stem from the prevalent association of meat with masculinity, and of veganism with femininity. Accordingly, linking vegan nutrition to masculinity might help to develop a favorable attitude toward plant-based diets in men. The present study examined the effects of a masculine framing of vegan dishes on men's attitudes toward vegan food and veganism, and explored whether adherence to traditional forms of masculinity might increase the effects of masculine framing.

Methods

We conducted an online experiment with a 2 (man vs. woman) x 2 (conventional vs. masculine framing) design, in which 593 adults participated. We measured participants' attitudes toward vegan dishes (dish ratings, hunger ratings) and veganism (veganism ratings, vegan scenarios ratings), the perceived suitability of the dishes for men and women as well as men's identification with new forms of masculinity.

Results

We found that a masculine framing of vegan dishes influenced the gender association of the dishes, weakening the link to femininity. However, masculine framing did not influence men's or women's attitudes toward the presented vegan dishes or veganism in general. Although the extent to which men identified with new forms of masculinity correlated positively with favorable attitudes toward veganism, new masculinity identification did - with an exception for the rating of the presented dishes - not moderate the effect of the experimental condition.

Discussion

Our findings suggest that the potency of a short-term intervention might not be sufficient to counterbalance the prevailing feminine connotations associated with veganism. Thus, we encourage further exploration of masculine framing to improve men's perception of vegan food and the vegan concept, but with stronger stimuli and/or longer intervention duration.
Improving the quality of the acoustic environment in neonatal intensive care units: a review of scientific literature and technological solutions
Authors: Lenzi Sara , Spagnol Simone , Özcan Elif
Published: October 2023

There is an increased awareness of how the quality of the acoustic environment impacts the lives of human beings. Several studies have shown that sound pollution has adverse effects on many populations, from infants to adults, in different environments and workplaces. Hospitals are susceptible environments that require special attention since sound can aggravate patients' health issues and negatively impact the performance of healthcare professionals. This paper focuses on Neonatal Intensive Care Units (NICU) as an especially sensitive case representing a hostile acoustic environment in which healthcare professionals have little awareness of how unwanted sounds impact the perceived quality of the soundscape. We performed a semi-systematic review of scientific literature on sound assessment studies in NICU from 2001. A thematic analysis was performed to identify emerging themes that informed the analysis of 27 technological solutions for the assessment of sound quality in indoor and outdoor environments. Solutions were categorized by functions and evaluation methods and grouped according to the characteristics of the design components, i.e., acquisition, computation, and communication strategies. Results highlight a lack of solutions to assess the qualitative characteristics of indoor environments such as NICU and forecast the footprint that different sound sources have on the indoor soundscape. Such solutions are urgently needed to empower healthcare professionals, and especially nurses, to actively modify and prevent the negative impact of unwanted sounds on NICU and critical care soundscape.
Efficiency and safety of vitrification of surplus oocytes following superovulation: a comparison of different clinical indications of oocyte cryopreservation in IVF/ICSI cycles
Authors: Fu Xiao , Zhang Yiting , Gao Shuli , Gao Shuzhe , Zhang Meng , Gao Shanshan , Ma Jinlong , Chen Zi-Jiang
Published: October 2023

Objective

To evaluate the effectiveness and safety of utilizing the small number of remaining vitrified oocytes after the failure of adequate fresh sibling oocytes. The outcome of present study would provide more comprehensive information about possible benefits or disadvantage to cryopreserve supernumerary oocytes for patients who have plenty oocytes retrieved.

Methods

This retrospective cohort study included 791 IVF/ICSI cycles using 6344 oocytes that had been vitrified in the Reproductive Hospital affiliated to Shandong University between January 2013 and December 2019.They were divided into three groups: SOC group (supernumerary oocytes cryopreservation), relative-MOC group (relative male factor-oocyte cryopreservation), and absolute-MOC group (absolute male factor-oocyte cryopreservation). Laboratory and clinical outcomes were analysed, and multivariate regression analysis was used to study the effect of different indications of vitrification on CLBR.

Results

The CLBR was highest in absolute-MOC, and lowest in SOC (39.0% vs 28.9%, P=0.006); however, after adjusting for confounding factors, the difference was not statistically significant. Multivariable regression analysis showed no impact of indications of vitrified oocytes on CLBR according to controlled age, BMI, preservation duration, use of donor sperm or not, use of PESA/TESA or not, number of oocytes retrieved, number of oocytes thawed, and oocyte survival rate. The preliminary data of safety showed no significant differences in the perinatal and neonatal outcoms after ET and FET between the SOC and MOC groups.

Conclusion

Different indications of vitrification did not affect CLBR. The CLBR of vitrified oocytes for different indications was correlated with age and number of warmed oocytes. For women who have plenty oocytes retrieved, the strategy of cryopreserving a small number of oocytes is a valuable option and might benefit them in the future. Additional data from autologous oocyte vitrification research employing a large-scale and variable-controlled methodology with extending follow-up will complement and clarify the current results.
Canagliflozin alters the gut, oral, and ocular surface microbiota of patients with type 2 diabetes mellitus
Authors: Wang Limin , Liang Chenghong , Song Xiaojian , Jia Xiaoyan , Wang Xiudan , Zhang Yun , Xie Qinyuan , Zheng Nan , Yuan Huijuan
Published: October 2023

Background

Modifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored.

Aim

This study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM.

Methods

In this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878).

Results

A noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota.

Clinical parameters

A significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05).

Gut microbiome

Treatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group.

Oral microbiota

After Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed.

Ocular surface microbiota

Post-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota.

Conclusion

Cana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.
The extremely small body size of Williamson’s mouse deer (Tragulus williamsoni) allows coexistence with sympatric larger ungulates through temporal avoidance
Authors: He Ru-Chuan , Wang Lin , Goodale Eben , Li Kai , Quan Rui-Chang
Published: October 2023

Research on the coexistence of congeneric species is essential for understanding community assemblages. Smaller competitors are expected to avoid larger ones, either spatially or temporally, to reduce interspecific competition. According to the spatial scaling law, the greater the difference in body size, the weaker the competitive interactions of the competitors. However, this is not confirmed in the guild of tropical forest ungulates. In this study, we assessed the competitive interactions of Williamson’s mouse deer (Tragulus williamsoni), an endangered species and one of the smallest ungulates in the world, with sympatric larger ungulates. We hypothesized that: 1) because of its extremely small body size, competition with the larger ungulates would be relatively weak, allowing spatial co-existence but still requiring temporal avoidance, and 2) the strength of avoidance would increases with decreasing differences in body size. We set up 238 camera traps from January 2017 to January 2021 to survey Williamson’s mouse deer and the sympatric larger ungulate species, that is, northern red muntjac (Muntiacus vaginalis), wild boar (Sus scrofa), Chinese serow (Capricornis milneedwardsii), and sambar (Rusa unicolor), in the protected areas of Mengla County, southwestern China. We then performed spatio-temporal analyses, including occupancy models, daily activity patterns, and a time interval analysis. Spatially, there was no significant avoidance. Temporally, Williamson’s mouse deer had different daily activity patterns and direct temporal avoidance of all larger ungulate species. The lack of spatial avoidance and strong temporal avoidance supported our first hypothesis, but the stronger avoidance of much larger species ran counter to our second hypothesis. Our results revealed the coexistence mechanism between Williamson’s mouse deer and sympatric larger ungulates and suggested that the difference in body size is limited in explaining the competitive interactions of tropical forest ungulates due to the effects of multiple ecological processes. This deepens our understanding of the relationship between species trait differences and community assembly in tropical forest ecosystems.
A syndrome differentiation model of TCM based on multi-label deep forest using biomedical text mining
Authors: Gong Lejun , Jiang Jindou , Chen Shiqi , Qi Mingming
Published: October 2023

Syndrome differentiation and treatment is the basic principle of traditional Chinese medicine (TCM) to recognize and treat diseases. Accurate syndrome differentiation can provide a reliable basis for treatment, therefore, establishing a scientific intelligent syndrome differentiation method is of great significance to the modernization of TCM. With the development of biomdical text mining technology, TCM has entered the era of intelligence that based on data, and model training increasingly relies on the large-scale labeled data. However, it is difficult to form a large standard data set in the field of TCM due to the low degree of standardization of TCM data collection and the privacy protection of patients’ medical records. To solve the above problem, a multi-label deep forest model based on an improved multi-label ReliefF feature selection algorithm, ML-PRDF, is proposed to enhance the representativeness of features within the model, express the original information with fewer features, and achieve optimal classification accuracy, while alleviating the problem of high data processing cost of deep forest models and achieving effective TCM discriminative analysis under small samples. The results show that the proposed model finally outperforms other multi-label classification models in terms of multi-label evaluation criteria, and has higher accuracy in the TCM syndrome differentiation problem compared with the traditional multi-label deep forest, and the comparative study shows that the use of PCC-MLRF algorithm for feature selection can better select representative features.
Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection
Authors: Jacobs Lotte M. C. , Wintjens Marieke S. J. N. , Nagy Magdolna , Willems Loes , ten Cate Hugo , Spronk Henri M. H. , van Kuijk Sander M. J. , Ghossein-Doha Chahinda , Netea Mihai G. , Groh Laszlo A. , van Petersen André S. , Warlé Michiel C.
Published: October 2023

Introduction

Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19.

Methods

Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured.

Results

167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes.

Discussion

In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies.

Trial registration

This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).
Antigen-dependent modulation of immune responses to antigen-Fc fusion proteins by Fc-effector functions
Authors: Richel Elie , Wagner Jannik T. , Klessing Stephan , Di Vincenzo Riccardo , Temchura Vladimir , Überla Klaus
Published: October 2023

Background

Fc-fusion proteins have been successfully developed for therapeutic purposes, but are also a promising platform for the fast generation and purification of immunogens capable of inducing strong humoral immune responses in preclinical immunization studies. As the Fc-portion of immunoglobulins fused to an antigen confers functional properties of the parental antibody, such as dimerization, binding to Fc-receptors and complement activation, several studies reported that Fc-fusion proteins elicit stronger antigen-specific antibody responses than the unfused antigen. However, dimerization or half-life extension of an antigen have also been described to enhance immunogenicity.

Methods

To explore the role of Fc-effector functions for the immunogenicity of fusions proteins of viral glycoproteins and Fc fragments, the HIV-1 gp120 and the RBD of SARS-CoV-2 were fused to the wild type muIgG2a Fc fragment or mutants with impaired (LALA-PG) or improved (GASDIE) Fc-effector functions.

Results

Immunization of BALB/c mice with DNA vaccines encoding gp120 – Fc LALA-PG induced significantly higher antigen-specific antibody responses than gp120 – Fc WT and GASDIE. In contrast, immunization with DNA vaccines encoding the RBD fused to the same Fc mutants, resulted in comparable anti-RBD antibody levels and similar neutralization activity against several SARS-CoV-2 variants.

Conclusion

Depending on the antigen, Fc-effector functions either do not modulate or suppress the immunogenicity of DNA vaccines encoding Fc-antigen fusion proteins.
Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome
Authors: Jensen Mary Ellen , Harrell Katelin , McBride Jeffrey D.
Published: October 2023

Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)—a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component (“naked granulomas”), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously.
Beyond discards: cascading socio-economic and environmental effects of a commercial aggregate landings program in Rhode Island
Authors: Livermore Julia
Published: October 2023

Flexible approaches to commercial fisheries harvest have been designed to meet management objectives. Rights-based management tools have been problematic for fishing businesses in certain scenarios, whereas aggregate landings approaches may offer similar flexibility while avoiding pitfalls like industry consolidation. This study evaluates a Rhode Island pilot aggregate landings program for summer flounder (Paralichthys dentatus) and black sea bass (Centropristis striata) from the perspective of the pilot program participants. Semi-structured interviews were conducted with participating commercial harvesters. Fishery-dependent data were also analyzed to supplement harvesters’ responses. Interview respondents overwhelmingly supported the aggregate landings approach and described benefits directly from the program, including cost savings, reduced discards, and improved safety. The program also led to increased average weekly harvest of both species and a slight increase in the price of catch for black sea bass for program participants. The aggregate landings approach encouraged fishers to take on less risk through added flexibility in when they chose to fish, while still maximizing their utility. Although the original goals of the program were to reduce regulatory discards and make businesses more efficient, it also resulted in improvements to fishers’ well-being, suggesting that aggregate landings approaches should be considered for other fisheries.
Suitable ultrasound screening method for older adults with disability to identify low muscle mass
Authors: Ding Huaying , Lin Xia , Huang Sha , Liao Jie , Li Zhouyu , Chen Lanlan , Zhu Li , Xie Yukuan , Nie Qian , Chen Xiaoyan
Published: October 2023

Objective

This study aimed to investigate the accuracy and consistency of different ultrasound protocols for the measurement of gastrocnemius muscle (GM) thickness and to identify a suitable ultrasound scheme that can be used to detect the low muscle mass in older with disability.

Materials and methods

In this cross-sectional study, each participant underwent three different ultrasound protocols for the measurement of the GM thickness, and each measurement was repeated three times. The three measurement schemes were as follows: method A, lying on the examination bed in a prone position with legs stretched and relaxed and feet hanging outside the examination bed; method B, lateral right side lying position with legs separated (left leg flexed and right leg in a relaxed state); and method C, right side lying position with legs together and lower limb muscles in a relaxed state. The low muscle mass was determined by averaging two or three measurements of the GM thickness determined using different sonographic protocols.

Results

The study included 489 participants. The difference in the prevalence of low muscle mass identified between two and three replicates of the same measurement protocol ranged from 0 to 1.3%. Considering the three repeated measurements of the method A as the reference, the area under the curve (AUC) in different measurement schemes were 0.977-1 and 0.973-1 in males and females, respectively. Furthermore, male and female Kappa values from low to high were 0.773, 0.801, 0.829, 0.839, and 0.967 and 0.786, 0.794, 0.804, 0.819, and 0.984, respectively.

Conclusion

Different ultrasound measurement protocols showed high accuracy and consistency in identifying low muscle mass. Repeating the measurements two or three times was found to be feasible.
Application of hypoxia-mesenchymal stem cells in treatment of anaerobic bacterial wound infection: wound healing and infection recovery
Authors: Andalib Elahe , Kashfi Mojtaba , Mahmoudvand Golnaz , Rezaei Elaheh , Mahjoor Mohamad , Torki Alireza , Afkhami Hamed
Published: October 2023

Mesenchymal stromal cells, commonly referred to as MSCs, are a type of multipotent stem cells that are typically extracted from adipose tissue and bone marrow. In the field of tissue engineering and regenerative medicine, MSCs and their exosomes have emerged as revolutionary tools. Researchers are now devoting greater attention to MSCs because of their ability to generate skin cells like fibroblasts and keratinocytes, as well as their distinctive potential to decrease inflammation and emit pro-angiogenic molecules at the site of wounds. More recent investigations revealed that MSCs can exert numerous direct and indirect antimicrobial effects that are immunologically mediated. Collectively, these antimicrobial properties can remove bacterial infections when the MSCs are delivered in a therapeutic setting. Regardless of the positive therapeutic potential of MSCs for a multitude of conditions, transplanted MSC cell retention continues to be a major challenge. Since MSCs are typically administered into naturally hypoxic tissues, understanding the impact of hypoxia on the functioning of MSCs is crucial. Hypoxia has been postulated to be among the factors determining the differentiation of MSCs, resulting in the production of inflammatory cytokines throughout the process of tissue regeneration and wound repair. This has opened new horizons in developing MSC-based systems as a potent therapeutic tool in oxygen-deprived regions, including anaerobic wound infection sites. This review sheds light on the role of hypoxia-MSCs in the treatment of anaerobic bacterial wound infection in terms of both their regenerative and antimicrobial activities.
Three E2F target-related genes signature for predicting prognosis, immune features, and drug sensitivity in hepatocellular carcinoma
Authors: Zhang Baozhu , Chang Boyang , Wang Lu , Xu Yuzhong
Published: October 2023

Background: Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2Fs) target pathway is thought to have a major role in tumor growth. This study aimed to identify a predictive E2F target signature and facilitate individualized treatment for HCC patients.

Methods: We constructed an E2F target-related gene profile using univariate COX and LASSO regression models and proved its predictive efficacy in external cohorts. Furthermore, we characterized the role of the E2F target pathway in pathway enrichment, immune cell infiltration, and drug sensitivity of HCC.

Results: Lasso Cox regression created an E2F target-related gene signature of GHR, TRIP13, and CDCA8. HCC patients with high risk were correlated with shorter survival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs.

Conclusion: Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research.
Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: a study protocol for a randomized controlled trial
Authors: Tang Zhiqing , Liu Tianhao , Liu Ying , Han Kaiyue , Su Wenlong , Zhao Jingdu , Chi Qianqian , Zhang Xiaonian , Zhang Hao
Published: October 2023

Background

Upper limb motor recovery is one of the important goals of stroke rehabilitation. Intermittent theta burst stimulation (iTBS), a new type of repetitive transcranial magnetic stimulation (rTMS), is considered a potential therapy. However, there is still no consensus on the efficacy of iTBS for upper limb motor dysfunction after stroke. Stimulus dose may be an important factor affecting the efficacy of iTBS. Therefore, we aim to investigate and compare the effects and neural mechanisms of three doses of iTBS on upper limb motor recovery in stroke patients, and our hypothesis is that the higher the dose of iTBS, the greater the improvement in upper limb motor function.

Methods

This prospective, randomized, controlled trial will recruit 56 stroke patients with upper limb motor dysfunction. All participants will be randomized in a 1:1:1:1 ratio to receive 21 sessions of 600 pulses active iTBS, 1,200 pulses active iTBS, 1,800 pulses active iTBS, or 1,800 pulses sham iTBS in addition to conventional rehabilitation training. The primary outcome is the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score from baseline to end of intervention, and the secondary outcomes are the Wolf Motor Function Test (WMFT), Grip Strength (GS), Modified Barthel Index (MBI), and Stroke Impact Scale (SIS). The FMA-UE, MBI, and SIS are assessed pre-treatment, post-treatment, and at the 3-weeks follow-up. The WMFT, GS, and resting-state functional magnetic resonance imaging (rs-fMRI) data will be obtained pre- and post-treatment.

Discussion

The iTBS intervention in this study protocol is expected to be a potential method to promote upper limb motor recovery after stroke, and the results may provide supportive evidence for the optimal dose of iTBS intervention.
The effects of NAD+ precursor (nicotinic acid and nicotinamide) supplementation on weight loss and related hormones: a systematic review and meta-regression analysis of randomized controlled trials
Authors: Baichuan You , Gomes Reis Marcela , Tavakoli Sogand , Khodadadi Navideh , Sohouli Mohammad Hassan , Sernizon Guimarães Nathalia
Published: October 2023

Background

Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of nicotinamide adenine dinucleotide (NAD+) precursor. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on weight loss, adiponectin, and leptin.

Methods

Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss and related hormones effects of NAD+ precursor. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.

Results

Twenty two treatment arms with 5,144 participants’ were included in this systematic review and meta-regression analysis. The pooled findings showed that NAD+ precursor supplementation has an effect on lowering BMI (weighted mean difference (WMD): −0.19 kg/m2, 95% confidence interval (CI): −0.29 to −0.09, p < 0.001) and increasing adiponectin (WMD: 1.59 μg/mL, 95% CI: 0.49 to 2.68, p = 0.004) in humans compared with control groups. However, no significant effect was observed on body weight and leptin. There was a significant relationship between doses of intervention with changes in BMI. In addition, subgroup analysis showed that BMI reduction was greater when receiving nicotinic acid (NA) supplementation than nicotinamide (NE) supplementation.

Conclusion

NAD+ precursor had significant effects on weight management with the reduction of BMI and increasing adiponectin.
The utility of high-frequency 18 MHz ultrasonography for preoperative evaluation of acral melanoma thickness in Chinese patients
Authors: Yu Nianzhou , Huang Kai , Li Yixin , Jiang Zixi , Liu Siliang , Liu Yuancheng , Liu Xiaowan , Chen Zeyu , He Renliang , Wei Tianhong
Published: October 2023

Background

Despite the increasing use of preoperative ultrasound evaluation for melanoma, there is limited research on the use of this technique for Acral Melanoma (AM).

Methods

This retrospective study analyzed the electronic medical records of patients who underwent preoperative evaluation for cutaneous melanoma maximum thickness using an 18 MHz probe and histopathological examination between December 2017 and March 2021 at the Department of Dermatology in Xiangya Hospital, Central South University.

Results

A total of 105 patients were included in the study. The mean tumor thickness was 3.9 mm (s.d., 2.3), with 63% of the specimens showing ulceration and 44 patients showing lymph node metastasis. The results showed a good correlation between the high-frequency ultrasonography (HFUS) and histopathological thickness measurements, with a Spearman’s correlation coefficient of 0.83 [(95% CI 0.73–0.90) (P < 0.001)]. The positive predictive value (PPV) of sonography in identifying tumor thickness was also found to be high.

Conclusion

Our study suggests that high-frequency 18 MHz ultrasonography is an effective tool for the preoperative evaluation of AM thickness. The HFUS measurements correlated well with the histopathological thickness measurements, making it a valuable and reliable method for clinicians to assess the thickness of melanoma lesions preoperatively.
Application of FGD-BCEL loss function in segmenting temporal lobes on localized CT images for radiotherapy
Authors: Wen Xiaobo , Liang Bing , Zhao Biao , Hu Xiaokun , Yuan Meifang , Hu Wenchao , Liu Ting , Yang Yi , Xing Dongming
Published: October 2023

Objectives

The aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation.

Methods

Localized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set (n = 49), the validation set (n = 7), and the test set (n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework.

Results

With the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples.

Conclusions

For the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.
Can we predict discordant RECIST 1.1 evaluations in double read clinical trials?
Authors: Beaumont Hubert , Iannessi Antoine
Published: October 2023

Background

In lung clinical trials with imaging, blinded independent central review with double reads is recommended to reduce evaluation bias and the Response Evaluation Criteria In Solid Tumor (RECIST) is still widely used. We retrospectively analyzed the inter-reader discrepancies rate over time, the risk factors for discrepancies related to baseline evaluations, and the potential of machine learning to predict inter-reader discrepancies.

Materials and methods

We retrospectively analyzed five BICR clinical trials for patients on immunotherapy or targeted therapy for lung cancer. Double reads of 1724 patients involving 17 radiologists were performed using RECIST 1.1. We evaluated the rate of discrepancies over time according to four endpoints: progressive disease declared (PDD), date of progressive disease (DOPD), best overall response (BOR), and date of the first response (DOFR). Risk factors associated with discrepancies were analyzed, two predictive models were evaluated.

Results

At the end of trials, the discrepancy rates between trials were not different. On average, the discrepancy rates were 21.0%, 41.0%, 28.8%, and 48.8% for PDD, DOPD, BOR, and DOFR, respectively. Over time, the discrepancy rate was higher for DOFR than DOPD, and the rates increased as the trial progressed, even after accrual was completed. It was rare for readers to not find any disease, for less than 7% of patients, at least one reader selected non-measurable disease only (NTL). Often the readers selected some of their target lesions (TLs) and NTLs in different organs, with ranges of 36.0-57.9% and 60.5-73.5% of patients, respectively. Rarely (4-8.1%) two readers selected all their TLs in different locations. Significant risk factors were different depending on the endpoint and the trial being considered. Prediction had a poor performance but the positive predictive value was higher than 80%. The best classification was obtained with BOR.

Conclusion

Predicting discordance rates necessitates having knowledge of patient accrual, patient survival, and the probability of discordances over time. In lung cancer trials, although risk factors for inter-reader discrepancies are known, they are weakly significant, the ability to predict discrepancies from baseline data is limited. To boost prediction accuracy, it would be necessary to enhance baseline-derived features or create new ones, considering other risk factors and looking into optimal reader associations.