bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Sentimen Terhadap Dampak Inflasi di Indonesia Menggunakan Metode Multinomial Naïve Bayes
Authors: Wijaya Aldi Tri , Hermawan Arief
Published: August 2023

Inflasi yang terjadi di seluruh dunia termasuk negara Indonesia mengakibatkan masalah bagi masyarakat maupun negara, terjadinya ketidakstabilan ekonomi negara dan meningkatnya pengangguran dikarenakan banyaknya pengurangan karyawan kerja, selain itu dengan kelangkaan minyak terutama bahan bakar kendaraan salah satu faktor yang mendorong kenaikan inflasi sehingga mengakibatkan harga-harga barang dan sandang mengalami kenaikan yang signifikan, dari persoalan tersebut menimbulkan opini-opini masyarakat pada jejaring sosial khususnya twitter dari timbulnya masalah inflasi. Maka dibuatkan sistem untuk melakukan analisis sentimen dari masalah kondisi Inflasi Indonesia. Proses sistem memerlukan data tweet dengan jumlah 1725 tweet hasil dari proses crawling data twitter menggunakan bantuan library python yaitu tweepy pada masing-masing kata kunci inflasi. Algoritma naïve bayes clasiffier dengan model multinomialnb sebagai metode untuk melakukan klasifikasi. Hasil klasifikasi dari search key inflasi indonesia mengandung beberapa kelas yaitu positif, negatif dan netral. Proses penelitian diuji menggunakan beberapa skenario pembagian data yaitu 90:10, 80:20, 70:30, untuk tingkat akurasi terbaik dihasilkan menggunakan skenario 90% data train dan 10% data test mendapatkan hasil akurasi 75,5%, precision 75%, f1-score 75% dan recall 74%.
Fusi Algoritma K-Means dan CNN untuk Klasifikasi Emosi pada Anak
Authors: Zhafirah Fildzah Aure Gehara , Rokhana Rika , Sigit Riyanto , Dewantara Bima Sena Bayu
Published: August 2023

Emosi adalah perasaan yang diarahkan pada seseorang ataupun sesuatu yang bisa menyebabkan sesorang bertindak atau mengekspresikan diri dan dapat dipicu secara internal ataupun eksternal. Ekspresi wajah merupakan salah satu cara termudah untuk mengetahui emosi seseorang, namun terkadang seseorang dapat mengontrol dan memanipulasi ekspresi wajah mereka sehingga tidak sesuai dengan apa yang dialami. Oleh karena itu, penelitian ini mengembangkan sistem yang dapat mengidentifikasi emosi anak tidak hanya berdasarkan wajah tetapi juga berdasarkan perubahan kondisi tubuhnya. Penelitian ini menggunakan metode klasifikasi Convolutional Neural Network (CNN) dan juga metode clusterisasi K-Means. Penggunaan 2 metode pada penelitian ini berfungsi untuk memperkuat akurasi sistem. Metode K-Means digunakan untuk mengidentifikasi emosi berdasarkan detak jantung dan konduktivitas kulit sedangkan Metode CNN digunakan untuk mengidentifikasi emosi berdasarkan ekspresi wajah. Hasil yang diperoleh dari kedua metode tersebut akan diproses menggunakan metode fusi yang aturannya disesuaikan berdasarkan hasil pengamatan dan pengukuran, sehingga dapat diprediksi emosi pada anak berdasarkan parameter detak jantung, ekspresi wajah, dan konduktivitas kulit. Anak dengan umur 6 hingga 12 tahun digunakan sebagai subjek pada penelitian ini. Dari penelitian ini berhasil didapatkan hasil prediksi emosi anak dengan akurasi keberhasilan sebesar 80%.
NP on Logarithmic Space
Authors: Vega Frank
Published: August 2023

$P$ versus $NP$ is considered as one of the most important open problems in computer science. This consists in knowing the answer of the following question: Is $P$ equal to $NP$? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the $P$ versus $NP$ problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity classes are $L$ and $NL$. Whether $L = NL$ is another fundamental question that it is as important as it is unresolved. We prove that $NP \subseteq NSPACE(\log^{2} n)$ just using logarithmic space reductions.
NP on Logarithmic Space: Mediterranean International Conference of Pure & Applied Mathematics and Related Area (MICOPAM 2023)
Authors: Vega Frank
Published: August 2023

The $P$ versus $NP$ problem consists in knowing the answer of the following question: Is $P$ equal to $NP$? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the $P$ versus $NP$ problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity classes are $DSPACE(S(n))$ and $NSPACE(S(n))$ for every space-constructible function $S(n)$. We prove that $NP \subseteq NSPACE(\log^{2} n)$ just using logarithmic space reductions.
On Solé and Planat criterion for the Riemann Hypothesis: Mediterranean International Conference of Pure & Applied Mathematics and Related Area (MICOPAM 2023)
Authors: Vega Frank
Published: August 2023

The Riemann Hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. In 2011, Solé and Planat stated that the Riemann hypothesis is true if and only if the inequality $\zeta(2) \cdot \prod_{q\leq q_{n}} (1+\frac{1}{q}) > e^{\gamma} \cdot \log \theta(q_{n})$ holds for all prime numbers $q_{n}> 3$, where $\theta(x)$ is the Chebyshev function, $\gamma \approx 0.57721$ is the Euler-Mascheroni constant, $\zeta(x)$ is the Riemann zeta function and $\log$ is the natural logarithm. We prove that the Riemann Hypothesis is true using this criterion.
On Solé and Planat Criterion for the Riemann Hypothesis
Authors: Vega Frank
Published: August 2023

There are several statements equivalent to the famous Riemann hypothesis. In 2011, Solé and Planat stated that the Riemann hypothesis is true if and only if the inequality $\zeta(2) \cdot \prod_{q\leq q_{n}} (1+\frac{1}{q}) > e^{\gamma} \cdot \log \theta(q_{n})$ holds for all prime numbers $q_{n}> 3$, where $\theta(x)$ is the Chebyshev function, $\gamma \approx 0.57721$ is the Euler-Mascheroni constant, $\zeta(x)$ is the Riemann zeta function and $\log$ is the natural logarithm. In this note, using Solé and Planat criterion, we prove that the Riemann hypothesis is true.
Integration of human stem cell-derived in vitro systems and mouse preclinical models identifies complex pathophysiologic mechanisms in retinal dystrophy
Authors: Jones Melissa K. , Orozco Luz D. , Qin Han , Truong Tom , Caplazi Patrick , Elstrott Justin , Modrusan Zora , Chaney Shawnta Y. , Jeanne Marion
Published: August 2023

Rare DRAM2 coding variants cause retinal dystrophy with early macular involvement via unknown mechanisms. We found that DRAM2 is ubiquitously expressed in the human eye and expression changes were observed in eyes with more common maculopathy such as Age-related Macular Degeneration (AMD). To gain insights into pathogenicity of DRAM2-related retinopathy, we used a combination of in vitro and in vivo models. We found that DRAM2 loss in human pluripotent stem cell (hPSC)-derived retinal organoids caused the presence of additional mesenchymal cells. Interestingly, Dram2 loss in mice also caused increased proliferation of cells from the choroid in vitro and exacerbated choroidal neovascular lesions in vivo. Furthermore, we observed that DRAM2 loss in human retinal pigment epithelial (RPE) cells resulted in increased susceptibility to stress-induced cell death in vitro and that Dram2 loss in mice caused age-related photoreceptor degeneration. This highlights the complexity of DRAM2 function, as its loss in choroidal cells provided a proliferative advantage, whereas its loss in post-mitotic cells, such as photoreceptor and RPE cells, increased degeneration susceptibility. Different models such as human pluripotent stem cell-derived systems and mice can be leveraged to study and model human retinal dystrophies; however, cell type and species-specific expression must be taken into account when selecting relevant systems.
State-resolved studies of CO2 sticking to CO2 ice
Authors: Jansen Charlotte , Juurlink Ludo B. F.
Published: August 2023

Internal vibrations may affect the adsorption, scattering, and reactions of molecules impinging onto a surface. The energy of the ν3 antisymmetric stretch vibration of CO2 slightly exceeds the desorption energy of CO2 bound to CO2 ice. We use supersonic molecular beam techniques and rovibrationally state-resolved excitation to determine whether this vibration affects condensation of gas phase CO2 to its ice. We detect sticking and CO2 ice formation using RAIRS and quantify the sticking probability using the King and Wells method with modulation of the vibrational excitation and Fourier transform based detection. We find that the influence of this vibration on the structure of the formed ice and on the sticking probability is negligible under our conditions. Based on our detection limit, we quantify the weighted average sticking probability at approximately 0.9 and the difference between the state-resolved and weighted average sticking probability as below 0.5%.
Protective role of CFTR during fungal infection of cystic fibrosis bronchial epithelial cells with Aspergillus fumigatus
Authors: Illek Beate , Fischer Horst , Machen Terry E. , Hari Gopika , Clemons Karl V. , Sass Gabriele , Ferreira Jose A. G. , Stevens David A.
Published: August 2023

Lung infection with the fungus Aspergillus fumigatus (Af) is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function. We established a fungal epithelial co-culture model to examine the impact of Af infection on CF bronchial epithelial barrier function using Af strains 10AF and AF293-GFP, and the CFBE41o- cell line homozygous for the F508del mutation with (CF+CFTR) and without (CF) normal CFTR expression. Following exposure of the epithelial surface to Af conidia, formation of germlings (early stages of fungal growth) was detected after 9-12 hours and hyphae (mature fungal growth) after 12-24 hours. During fungal morphogenesis, bronchial epithelial cells showed signs of damage including rounding, and partial detachment after 24 hours. Fluorescently labeled conidia were internalized after 6 hours and more internalized conidia were observed in CF compared to CF+CFTR cells. Infection of the apical surface with 10AF conidia, germlings, or hyphae was performed to determine growth stage-specific effects on tight junction protein zona occludens protein 1 (ZO-1) expression and transepithelial electrical resistance (TER). In response to infection with conidia or germlings, epithelial barrier function degraded time-dependently (based on ZO-1 immunofluorescence and TER) with a delayed onset in CF+CFTR cell monolayers and required viable fungi and apical application. Infection with hyphae caused an earlier onset and faster rate of decline in TER compared to conidia and germlings. Gliotoxin, a major Af virulence factor, caused a rapid decline in TER and induced a transient chloride secretory response in CF+CFTR but not CF cells. Our findings suggest growth and internalization of Af result in deleterious effects on bronchial epithelial barrier function that occurred more rapidly in the absence of CFTR. Bronchial epithelial barrier breakdown was time-dependent and morphotype-specific and mimicked by acute administration of gliotoxin. Our study also suggests a protective role for CFTR by turning on CFTR-dependent chloride transport in response to gliotoxin, a mechanism that will support mucociliary clearance, and could delay the loss of epithelial integrity during fungal development in vivo.
The lung-gut crosstalk in respiratory and inflammatory bowel disease
Authors: Du Baoxiang , Fu Yan , Han Yuxiu , Sun Qihui , Xu Jinke , Yang Yong , Rong Rong
Published: August 2023

Both lung and gut belong to the common mucosal immune system (CMIS), with huge surface areas exposed to the external environment. They are the main defense organs against the invasion of pathogens and play a key role in innate and adaptive immunity. Recently, more and more evidence showed that stimulation of one organ can affect the other, as exemplified by intestinal complications during respiratory disease and vice versa, which is called lung-gut crosstalk. Intestinal microbiota plays an important role in respiratory and intestinal diseases. It is known that intestinal microbial imbalance is related to inflammatory bowel disease (IBD), this imbalance could impact the integrity of the intestinal epithelial barrier and leads to the persistence of inflammation, however, gut microbial disturbances have also been observed in respiratory diseases such as asthma, allergy, chronic obstructive pulmonary disease (COPD), and respiratory infection. It is not fully clarified how these disorders happened. In this review, we summarized the latest examples and possible mechanisms of lung-gut crosstalk in respiratory disease and IBD and discussed the strategy of shaping intestinal flora to treat respiratory diseases.
Renin–angiotensin system inhibitors reduce cardiovascular mortality in hypertensive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry
Authors: Basile Christian , Mancusi Costantino , Franzone Anna , Avvedimento Marisa , Bardi Luca , Angellotti Domenico , Castiello Domenico Simone , Mariani Andrea , Manzo Rachele , De Luca Nicola , Cirillo Plinio , De Simone Giovanni , Esposito Giovanni
Published: August 2023

Objectives

Arterial hypertension is associated with the triggering of the renin–angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality.

Methods

We enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan–Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment.

Results

Among the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23–0.81, p = 0.009). This association remained stable after both multivariable adjustment and propensity score matching.

Conclusion

In a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment.
The digitized chronic disease management model: scalable strategies for implementing standardized healthcare and big data analytics in Shanghai
Authors: Sui Mengyun , Cheng Minna , Zhang Sheng , Wang Yuheng , Yan Qinghua , Yang Qinping , Wu Fei , Xue Long , Shi Yan , Fu Chen
Published: August 2023

Background

Chronic disease management (CDM) falls under production relations, and digital technology belongs to the realm of productivity. Production relations must adapt to the development of productivity. Simultaneously, the prevalence and burden of chronic diseases are becoming increasingly severe, leveraging digital technology to innovate chronic disease management model is essential.

Methods

The model was built to cover experts in a number of fields, including administrative officials, public health experts, information technology staff, clinical experts, general practitioners, nurses, metrologists. Integration of multiple big data platforms such as General Practitioner Contract Platform, Integrated Community Multimorbidity Management System and Municipal and District-Level Health Information Comprehensive Platform. This study fully analyzes the organizational structure, participants, service objects, facilities and equipment, digital technology, operation process, etc., required for new model in the era of big data.

Results

Based on information technology, we build Integrated Community Multimorbidity Care Model (ICMCM). This model is based on big data, is driven by “technology + mechanism,” and uses digital technology as a tool to achieve the integration of services, technology integration, and data integration, thereby providing patients with comprehensive people-centered services. In order to promote the implementation of the ICMCM, Shanghai has established an integrated chronic disease management information system, clarified the role of each module and institution, and achieved horizontal and vertical integration of data and services. Moreover, we adopt standardized service processes and accurate blood pressure and blood glucose measurement equipment to provide services for patients and upload data in real time. On the basis of Integrated Community Multimorbidity Care Model, a platform and index system have been established, and the platform's multidimensional cross-evaluation and indicators are used for management and visual display.

Conclusions

The Integrated Community Multimorbidity Care Model guides chronic disease management in other countries and regions. We have utilized models to achieve a combination of services and management that provide a grip on chronic disease management.
The relationship between triglyceride-glucose index and albuminuria in United States adults
Authors: Wang Zhaoxiang , Qian Han , Zhong Shao , Gu Tian , Xu Mengjiao , Yang Qichao
Published: August 2023

Purpose

Triglyceride-glucose (TyG) index is a simple and reliable indicator of metabolic dysfunction. We aimed to investigate a possible relationship between TyG index and albuminuria in the United States adult population.

Methods

This cross-sectional study was conducted among adults with complete TyG index and urinary albumin/urinary creatinine (UACR) from 2011-2018 National Health and Nutrition Examination Survey (NHANES). The independent relationship between TyG index and albuminuria (UACR>30mg/g) was evaluated. TyG index was compared with insulin resistance represented by homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic syndrome. Subgroup analysis was also performed.

Results

A total of 9872 participants were included in this study, and the average TyG index was 8.53 ± 0.01. The proportion of albuminuria gradually increased with the increase of TyG index quartile interval. Elevated TyG index was independently associated with albuminuria, and this association persisted after additional adjustments for HOMA-IR or dichotomous metabolic syndrome. The area under the ROC curve (AUC) of TyG index was larger than that of log (HOMA-IR). Subgroup analysis suggested that the relationship between TyG index and albuminuria is of greater concern in age<60, overweight/obese, diabetic, and metabolic syndrome patients.

Conclusion

The TyG index may be a potential epidemiological tool to quantify the role of metabolic dysfunction, rather than just insulin resistance, in albuminuria in the United States adult population. Further large-scale prospective studies are needed to confirm our findings.
Osteoporosis and dermatoporosis: a review on the role of vitamin D
Authors: Romano Fiammetta , Serpico Domenico , Cantelli Mariateresa , Di Sarno Antonella , Dalia Carmine , Arianna Rossana , Lavorgna Mariarosaria , Colao Annamaria , Di Somma Carolina
Published: August 2023

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body’s capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.
Methodological introduction to the carbon footprint evaluation of intermodal transport
Authors: Bielenia Małgorzata , Dubisz Damian , Czermański Ernest
Published: August 2023

Managing logistics processes from an environmental perspective is increasingly important in international supply chains. Essential elements of global logistics are supply chains based on intermodal logistic units. The specificity of this type of shipment, which often involves several modes of transport, requires a precise definition of model boundaries and identification of specific factors determining the level of carbon footprint. This research is focused on identifying the specific emissivity level of each intermodal transport stage. The conducted study refers to the international emission evaluation guidelines gathered in the UN GHG Protocol. The carbon footprint (CF) evaluation commenced during the case study indicated the need to consider the specificity of the assigned modes of transport. Hence selected emission factors such as US DEFRA, US EPA, KOBiZE and UNFCCC were engaged for better carbon footprint evaluation related to each stage of the intermodal transport process. In the summary part, the environmental efficiency level of each mode of transport has been compared. The sea freight mode was indicated as the most efficient in terms of overall kg*eCO2 per kilometre. The study shows that intermodal maritime transport, taking into account the weight of the goods transported and the distance, is approximately 68% more efficient than road transport. However, it must be mentioned that to identify the differences comprehensively, transshipment operations must also be taken into account in each scenario. Further research steps and recommendations have been presented in the last section of this research.
Utilization of Sasa borealis seeds by Japanese field mouse: discovery of small-seed caching
Authors: Suzuki Hanami , Kajimura Hisashi
Published: August 2023

Bambusoideae are well-known for their large-scale flowering, seeding, and death events that occur after a vegetative phase that can often last for decades. These events are a valuable resource for many animals. Their mast seeding, in particular, affects rodent populations although the causal relationship between them is speculative. Moreover, the species of animals that utilize this resource also remains unclear. Therefore, this study aimed to examine the interaction between mast seeding plants and animals by conducting a feeding test using the seeds of a dwarf bamboo species (Sasa borealis) at different seasons and in different forest types. The results revealed that two mouse species, Apodemus speciosus and A. argenteus, utilized the seeds. They both predated as well as removed and sometimes buried the seeds, exhibiting small-seed caching behavior. Furthermore, A. speciosus was found to exhibit higher seed predation at covered sites and switching to removal behavior at the more exposed, open sites, while A. argenteus showed no distinguishable trends. Additionally, A. speciosus utilized the seeds less frequently in fall than in summer, suggesting a shift in diet towards acorns when available. Collectively, the results of this study provide novel insights into the interaction between mast seeding plants and the animals that utilize them.
Drivers of vegetation and soil determine natural regeneration of a single plantation at different slope positions
Authors: Liang Wenjun , Feng Yonghan , Li Fuming , Zhao Yi , Zhu Jingkang , Yao Jiafeng , Chang Chenlong , Wei Xi
Published: August 2023

Promoting natural regeneration in artificial forest ecosystems is crucial for sustainable management. Understanding the fundamental mechanisms and drivers of tree regeneration is the prerequisite for promoting it effectively. This study worked with Larix principis-rupprechtii, a species considered difficult to regenerate. Twenty-four sample plots measuring 30 m × 30 m were established, with eight plots at each of the lower, middle, and upper slope positions, respectively. Field investigation and multivariate analysis were performed to uncover the regeneration traits in the plantations with abundant seedlings on the continuous slope. The results revealed that ground diameter and height of the regeneration (RGD and RH) were larger at the lower slope, with significant positive correlations to available nitrogen (contribution rate, CR: 0.858) and slope (CR: 0.652). In contrast, regeneration density (RD), representing the quantity of regeneration, was greater at the middle slope. Its significant impact factors were slope position (CR: −0.648) and herb diversity, represented by Pielou index (CR: 0.961). Stand density had a significant negative effect on regeneration, particularly at the upper slope, with CRs of −0.842 and −0.764 to RGD/RH and RD, respectively. Common contribution was found among the factors, with the largest contribution groups being the topographical and soil factors (CR: 0.358). These findings provide valuable insights into the single species regeneration progress on northern mountainous slopes and offer essential information for developing facilitation methods for the natural regeneration in artificial forests.
Ets1 and IL17RA cooperate to regulate autoimmune responses and skin immunity to Staphylococcus aureus
Authors: Battaglia Michael , Sunshine Alex C. , Luo Wei , Jin Richard , Stith Alifa , Lindemann Matt , Miller Lloyd S. , Sinha Satrajit , Wohlfert Elizabeth , Garrett-Sinha Lee Ann
Published: August 2023

Introduction

Ets1 is a lymphoid-enriched transcription factor that regulates B- and Tcell functions in development and disease. Mice that lack Ets1 (Ets1 KO) develop spontaneous autoimmune disease with high levels of autoantibodies. Naïve CD4 + T cells isolated from Ets1 KO mice differentiate more readily to Th17 cells that secrete IL-17, a cytokine implicated in autoimmune disease pathogenesis. To determine if increased IL-17 production contributes to the development of autoimmunity in Ets1 KO mice, we crossed Ets1 KO mice to mice lacking the IL-17 receptor A subunit (IL17RA KO) to generate double knockout (DKO) mice.

Methods

In this study, the status of the immune system of DKO and control mice was assessed utilizing ELISA, ELISpot, immunofluorescent microscopy, and flow cytometric analysis of the spleen, lymph node, skin. The transcriptome of ventral neck skin was analyzed through RNA sequencing. S. aureus clearance kinetics in in exogenously infected mice was conducted using bioluminescent S. aureus and tracked using an IVIS imaging experimental scheme.

Results

We found that the absence of IL17RA signaling did not prevent or ameliorate the autoimmune phenotype of Ets1 KO mice but rather that DKO animals exhibited worse symptoms with striking increases in activated B cells and secreted autoantibodies. This was correlated with a prominent increase in the numbers of T follicular helper (Tfh) cells. In addition to the autoimmune phenotype, DKO mice also showed signs of immunodeficiency and developed spontaneous skin lesions colonized by Staphylococcus xylosus. When DKO mice were experimentally infected with Staphylococcus aureus, they were unable to clear the bacteria, suggesting a general immunodeficiency to staphylococcal species. γδ T cells are important for the control of skin staphylococcal infections. We found that mice lacking Ets1 have a complete deficiency of the γδ T-cell subset dendritic epidermal T cells (DETCs), which are involved in skin woundhealing responses, but normal numbers of other skin γδ T cells. To determine if loss of DETC combined with impaired IL-17 signaling might promote susceptibility to staph infection, we depleted DETC from IL17RA KO mice and found that the combined loss of DETC and impaired IL-17 signaling leads to an impaired clearance of the infection.

Conclusions

Our studies suggest that loss of IL-17 signaling can result in enhanced autoimmunity in Ets1 deficient autoimmune-prone mice. In addition, defects in wound healing, such as that caused by loss of DETC, can cooperate with impaired IL-17 responses to lead to increased susceptibility to skin staph infections.
A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia
Authors: Wang Shuhua , Li Yao , Tang Yanchun , Xie Weilin , Zhang Yue , Liu Qingyan
Published: August 2023

Objectives

This study aims to assess the efficacy of tofacitinib (TOF) plus iguratimod (IGU) in rheumatoid arthritis (RA) with usual interstitial pneumonia (UIP) (RA-UIP).

Methods

This was a prospective observational cohort, single-center study. Data from 78 RA-UIP patients treated with TOF plus IGU, IGU plus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and csDMARDs were analyzed. Clinically relevant responses in RA activity assessment, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) assessment at baseline and follow-up were compared between groups to evaluate the efficacy of TOF plus IGU.

Results

A total of 78 patients were followed up for at least 6 months after treatment. There were significant changes in sedimentation rate (ESR), C reactive protein (CRP), and disease activity score (DAS) 28-CRP during the follow-up within each treatment group, but there was no statistically significant difference between the two groups. After 6 months of TOF plus IGU treatment, forced vital capacity (FVC)% (84.7 ± 14.7 vs. 90.7 ± 15.4) and HRCT fibrosis score (7.3 ± 3.4 vs. 7.0 ± 5.6) showed a significant improvement compared to the csDMARDs group (P = 0.031, P = 0.015). The TOF plus IGU-treated patients had a significantly higher regression and lower deterioration than the csDMARDs-treated patients (P = 0.026, P = 0.026) and had a significantly higher response (regression + stability), with overall response rates of 66.7% (16/24) vs. 35.7% (10/28) (P = 0.027), respectively.

Conclusion

Our results indicate that TOF plus IGU can simultaneously relieve RA and RA-UIP and be better than the csDMARDs with a higher response rate in RA-UIP, which may be a potential choice for “dual treat-to-target”.
Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization
Authors: Yu Jiarong , Mao Zhigang , Zhou Zengding , Yuan Bo , Wang Xiqiao
Published: August 2023

Background

The mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.

Methods

We collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.

Results

HE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.

Conclusion

Microbiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management.
Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation
Authors: An Andy Yi , Baghela Arjun , Zhang Peter G. Y. , Blimkie Travis M. , Gauthier Jeff , Kaufmann Daniel Elias , Acton Erica , Lee Amy H. Y. , Levesque Roger C. , Hancock Robert E. W.
Published: August 2023

Introduction

Persistent symptoms after COVID-19 infection (“long COVID”) negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.

Methods

RNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.

Results

Compared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The “Resolved” endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of “Suppressive” and “Unresolved” endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.

Discussion

This study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes (“Unresolved” and “Suppressive”) were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment.
B vitamins supplementation induced shifts in phytoplankton dynamics and copepod populations in a subtropical coastal area
Authors: Wang Lin , Zhao Hancheng , Sanganyado Edmond , Liang Bo , Chen Xiaohan , Ma Qun , Lin Jianqing , Liu Wenhua
Published: August 2023

Introduction

B vitamins play a crucial role in shaping phytoplankton and zooplankton communities in marine ecosystems, yet their impact on community dynamics remains poorly understood.

Methods

We carried out in situ incubation experiments of B vitamins supplementation to explore the response pattern of phytoplankton and zooplankton community compositions.

Results

The results showed that vitamins B1, B2, B6 and B12 promoted the growth of phytoplankton, and the total Chl α in 87.5% of the supplemented B vitamin treatments showed a significant positive response (p < 0.05). Supplementation with these B vitamins significantly altered the community composition of phytoplankton, and 75% of the B vitamin-supplemented treatments showed an increase in the relative abundance of Minutocellus, Thalassiosirales, Odontella, Prymnesiales and Ditylum, considered mainly to be the result of B vitamin auxotrophy. In contrast, a significant decrease in Copepoda, including Calanoida and Cyclopoida, was observed in 87.5% of treatments. The observed shifts in community composition were attributed to the auxotrophy of certain diatoms and Prymnesiales for B vitamins. These shifts subsequently led to negative correlations (Spearman Rho < -0.8) between the abundance of these phytoplankton species and Copepoda populations.

Discussion

These findings advance our understanding of the complex interactions between micronutrient availability and plankton community dynamics.
Investigating the reliable acoustic path properties in a global scale
Authors: Liu Ying , Chen Cheng , Feng Xiao
Published: August 2023

Leveraging the benefits of low transmission loss and high signal-to-noise ratio, the reliable acoustic path (RAP) has been extensively employed in various underwater applications. In this study, we investigate RAP properties on a global scale. Acoustic simulations were conducted using global grids with a 0.25° × 0.25° spatial resolution, revealing that RAP range is positively correlated with ocean depth. Contrary to the prevailing belief that RAP properties are relatively unaffected by sound speed variations, our findings indicate that sound speed profiles (SSPs) play a crucial role in determining RAP properties by altering the RAP from 15 km to 50 km at a constant ocean depth of 4000 m. Additionally, the receiver angle can vary by nearly 5 km at the same source location due to SSP variations. Consequently, utilizing highly accurate SSPs can enhance the performance of underwater localization or communication systems that rely on RAP.
Management of acute COPD exacerbations in the internal medicine departments in Israel–a national survey
Authors: Bar-Shai Amir , Freund Ophir , Ovdat Tal , Segel Michael J. , Klempfner Robert , Elis Avishay
Published: August 2023

Background

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Acute exacerbations of COPD (AECOPD) drastically affect the clinical course of the disease. We aimed to evaluate the treatment of AECOPD in the internal medicine departments in Israel, nationwide.

Methods

The COPD Israeli survey (COPDIS) is the first national survey of patients admitted with AECOPD to internal medicine departments between 2017 and 2019. The survey includes prospective (n = 344) and retrospective (n = 1,166) data from 13 medical centers. We analyzed the pre-hospital, in-hospital, and pre-discharge care. Hospital evaluation, outcomes and discharge recommendations were assessed as well.

Results

The mean (±SD) age was 74 (±8) years, and 54% were males. 74% had comorbidities, and 88% had a diagnosis of COPD in their history. 70% of the patients received systemic steroids and antibiotics during their hospitalization, yet upon discharge, a lower rate of antibiotics prescription (10%) was found. Treatment with most long-acting bronchodilators dramatically dropped during admission, compared with their pre-hospital use. Overall, a long-acting bronchodilator (LABD) was used by 47% before admission, 28% in-hospital, and was prescribed to 54% at discharge. The discharge plan included a referral to pulmonary rehabilitation in only 11% and a smoking cessation recommendation in 43% of active smokers. The in-hospital mortality was 3% and the 1-year mortality rate was 25%. In multivariate analysis, performing a chest X-ray (adjusted OR 0.64, 95% CI 0.46–0.90) and prescribing LABD at discharge (AOR 0.73, 95% CI 0.57–0.95) were independent predictors for lower 1-year mortality.

Conclusion

Our results demonstrate AECOPD characteristics in Israel, and highlight several important gaps in AECOPD healthcare, which must be addressed to improve patient care.
Association of the gut microbiota with clinical variables in obese and lean Emirati subjects
Authors: Ahmad Manal Ali , Karavetian Mirey , Moubareck Carole Ayoub , Wazz Gabi , Mahdy Tarek , Venema Koen
Published: August 2023

Background

Growing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association in the Emirati population.

Methods

We explored differences in gut microbiota composition, particularly the Firmicutes/Bacteroidetes (F/B) ratio, between 43 obese and 31 lean adult Emirate counterparts, and its association with obesity markers, by using V3-V4 regions of 16 S ribosomal RNA gene sequencing data. Furthermore, we collected anthropometric and biochemical data.

Results

The two major phyla in obese and lean groups were Firmicutes and Bacteroidetes. We observed a significantly lower alpha diversity (Shannon index) in obese subjects and a significant difference in beta diversity and phylum and genus levels between the two groups. The obese group had higher abundances of Verrucomicrobia and Saccharibacteira and lower abundances of Lentisphaerae. Acidaminococcus and Lachnospira were more abundant in obese subjects and positively correlated with adiposity markers. No correlations were found between the gut microbiota and biochemical variables, such as fasting blood sugar, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.

Conclusion

We reveal significant differences in the gut microbiota between obese and lean adult Emiratis and an association between certain microbial genera of the gut microbiota and obesity. A better understanding of the interactions between gut microbes, diet, lifestyle, and health is warranted.
Causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomization study
Authors: Li Hanjing , Li Candong
Published: August 2023

Background

Studies showed that development of gut microbial dysbiosis has a close association with type 2 diabetes (T2D). It is not yet clear if there is a causal relationship between gut microbiota and T2D.

Methods

The data collected from the published genome-wide association studies (GWASs) on gut microbiota and T2D were analyzed. Two-sample Mendelian randomization (MR) analyses were performed to identify causal relationship between bacterial taxa and T2D. Significant bacterial taxa were further analyzed. To confirm the findings’ robustness, we performed sensitivity, heterogeneity, and pleiotropy analyses. A reverse MR analysis was also performed to check for potential reverse causation.

Results

By combining the findings of all the MR steps, we identified six causal bacterial taxa, namely, Lachnoclostridium, Oscillospira, Roseburia, Ruminococcaceae UCG003, Ruminococcaceae UCG010 and Streptococcus. The risk of T2D might be positively associated with a high relative abundance of Lachnoclostridium, Roseburia and Streptococcus but negatively associated with Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010. The results of MR analyses revealed that there were causal relationships between the six different genera and T2D. And the reverse MR analysis did not reveal any evidence of a reverse causality.

Conclusion

This study implied that Lachnoclostridium, Roseburia and Streptococcus might have anti-protective effect on T2D, whereas Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010 genera might have protective effect on T2D. Our study revealed that there was a causal relationship between specific gut microbiota genera and T2D.
Characterization of drought stress-mitigating Rhizobium from faba bean (Vicia faba L.) in the Chinese Qinghai-Tibet Plateau
Authors: Li Ping , Teng Changcai , Zhang Jinfa , Liu Yujiao , Wu Xuexia , He Tao
Published: August 2023

Rhizobium-driven symbiotic nitrogen-fixation in legumes not only benefits the growth but also enhances the stress tolerance of plants. Isolating and characterizing efficient, drought-tolerant rhizobia is a central goal for improving crop yields in arid regions. Here, we phylogenetically and biochemically characterized a novel strain of Rhizobium (‘QHCD11’) sampled from the root nodules of faba beans growing in an arid agricultural area in Qinghai-Tibet. We further tested the drought tolerance of the strain as well as of ‘Qingcan 14’ faba bean seedlings inoculated with it. Biochemical characterization involved bromothymol blue (BTB) tests, carbon metabolic profiling (Biolog GENIII), DNA–DNA hybridization (dDDH) assays, average nucleotide identity (ANI) analyses, and 16S rRNA sequencing. The result indicated that strain ‘QHCD11’ likely belongs to the Rhizobium indicum species. Drought stress tolerance was assessed by exposure to polyethylene glycol (PEG-6000) at concentrations of 0, 10, 15, and 20%. Increasing concentrations of PEG-6000 tended to result in decreased growth of ‘QHCD11’, although the strain performed better at 20% PEG 6000 than at 15%. Inoculation of drought-stressed faba bean seedlings with strain ‘QHCD11’ improved root vitality, chlorophyll content, antioxidant enzyme activities, and plant height. We suggest that inoculation of faba beans with ‘QHCD11’ is an environmentally sound strategy for mitigating crop drought stress in arid and semi-arid regions. In addition, the results presents here will benefit future studies into faba bean-rhizobia symbioses under drought stress.
Silibinin reduces in vitro methane production by regulating the rumen microbiome and metabolites
Authors: Liu Rui , Shen Yueyu , Ma Haokai , Li Yang , Lambo Modinat Tolani , Dai Baisheng , Shen Weizheng , Qu Yongli , Zhang Yonggen
Published: August 2023

This study used Silibinin as an additive to conduct fermentation experiments, wherein its effects on rumen gas production, fermentation, metabolites, and microbiome were analyzed in vitro. The silibinin inclusion level were 0 g/L (control group), 0.075 g/L, 0.15 g/L, 0.30 g/L, and 0.60 g/L (experimental group). Fermentation parameters, total gas production, carbon dioxide (CO2), methane (CH4), hydrogen (H2), and their percentages were determined. Further analysis of the rumen microbiome’s relative abundance and α/β diversity was performed on the Illumina NovaSeq sequencing platform. Qualitative and quantitative metabolomics analyses were performed to analyze the differential metabolites and metabolic pathways based on non-targeted metabolomics. The result indicated that with an increasing dose of silibinin, there was a linear reduction in total gas production, CO2, CH4, H2 and their respective percentages, and the acetic acid to propionic acid ratio. Concurrent with a linear increase in pH, when silibinin was added at 0.15 g/L and above, the total volatile fatty acid concentration decreased, the acetic acid molar ratio decreased, the propionic acid molar ratio increased, and dry matter digestibility decreased. At the same time, the relative abundance of Prevotella, Isotricha, Ophryoscolex, unclassified_Rotifera, Methanosphaera, Orpinomyces, and Neocallimastix in the rumen decreased after adding 0.60 g/L of silibinin. Simultaneously, the relative abundance of Succiniclasticum, NK4A214_group, Candidatus_Saccharimonas, and unclassified_Lachnospiraceae increased, altering the rumen species composition, community, and structure. Furthermore, it upregulated the ruminal metabolites, such as 2-Phenylacetamide, Phlorizin, Dalspinin, N6-(1,2-Dicarboxyethyl)-AMP, 5,6,7,8-Tetrahydromethanopterin, Flavin mononucleotide adenine dinucleotide reduced form (FMNH), Pyridoxine 5′-phosphate, Silibinin, and Beta-D-Fructose 6-phosphate, affecting phenylalanine metabolism, flavonoid biosynthesis, and folate biosynthesis pathways. In summary, adding silibinin can alter the rumen fermentation parameters and mitigate enteric methane production by regulating rumen microbiota and metabolites, which is important for developing novel rumen methane inhibitors.