bluuebunny/crossref_metadata_2025 huggingface dataset:
Identify the Development of Regional Ecotourism Potential Palopo City is Geospatial Based
Authors: Andi Jumardi  , Muhammad Ilyas  , Aryadi Nurfalaq  , Iin Karmila Putri
Published: January 2022

The purpose of the research, identifying geographical conditions and potential tourist attractions, the social conditions of the surrounding community, the prospect of ecotourism development. Methods in this research qualitative approach with survey research with geospatial and SWOT-based geography review approach. The results of this study produced 6 thematic maps including topographic maps, geological maps, land type maps, slope slopes, tourist attraction distribution maps, and distribution maps of public facilities by containing information about the most influential geographical conditions in supporting the development of mungkajang area as an ecotourism area. Potential tourist attractions owned by the Mungkajang area there are 9 attractions scattered in the Mungkajang area by offering its attractions Latuppa area offers waterfall and bathing tours in the river stream, Kambo area offers tourism and bathing, murante area bathing waterboom and Mungkajang area offers camping and shelter attractions in addition to tourist attractions in Mungkajang area equipped with various public facilities available. in tourist attractions and those outside of tourist attractions in the Mungkajang area. The social conditions of the community include people who live in the location of the Mungkajang area have the same understanding of ecotourism, approval of the development of Mungkajang ecotourism, interest in the development of Mungkajang ecotourism. Mungkajang area development strategy as ecotourism with a geographical review approach that supports among location factors, relief factors, climate factors, biogeography factors, soil factors, water factors, geological factors, population factors, attractiveness factors, infrastructure factors, accommodation factors and facility service factors, while from the results of SWOT analysis of strategies that must be carried out to maintain the sustainability of natural wealth, involving the community, Working with government agencies, maximizing information technology, offering tourism potential different from others, providing complete facilities as needed by tourists and building good cooperation between the government, private sector and the public in the utilization of SDA that has the potential as a tourist attraction.
Arrangement of Makassar City Water Sports Tour Packages based on Geographic Information Systems
Authors: Zulkifli Harahap  , Enos Julvirta  , Yayan Dian F.  , Muh. Musawantoro  , Darsyaf Hadi W.
Published: January 2022

This study aims to model the Tirta Tour package in Makassar City. This research method uses a qualitative approach, the data sources are obtained through surveys with field notes, interviews and documentation, while the data processing techniques use the help of ArcGIS 10.5 software. The data collection techniques used in this study are: Focus Group Discussion (FGD), interviews, study comparison and literature study were used for qualitative data. Based on the processed data, it was found as follows: 1) Water tourism potential in Makassar City as a result of analysis 3A: Accessibility, Amenity and Activities in general, the cluster of islands in the Spermonde Archipelago has the potential to become superior marine tourism with current conditions it can be said to be natural. heritage landscapes. 2) Mapping model for Tirta Tour Packages in Makassar City in the form of Tirta Travel Routes with a Stopover Movement Pattern with 4 Tourist Attractions. This study recommends the preparation of an online water tourism information system for Makassar City so that it can be accessed anytime and anywhere.
An Illustrative Review of Positional Asphyxiation in Infants Secured Upright in Car Seats
Authors: L. Alston Margaret , Jambulingam Malliga , Binte Haidary Uzma , Hunt Ariel , Thomas David , Bronner Yvonne
Published: January 2022

Sudden Unexpected Infant Death (SUID) includes the full spectrum of all causes of infant death, which include “Determined” causes [e.g. Sudden Infant Death Syndrome (SIDS) at 42% and Accidental Suffocation and Strangulation at 24%], as well as “Undetermined” causes at 34% [1]. Literature is replete with studies that address the risk factors associated with SIDS, accounting for at least 42% of infant mortality,[1] but scarcely do published reports address risk factors associated with Positional Asphyxia (PA).This illustrative narrative addresses the 2.8 – 3.0% (98-105) healthy infants who have no pre-existing medical conditions, including prematurity, who die from SUID primarily in car seats, and whose suspected cause of death is PA. Webster’s Dictionary defines PA as, “A condition of deficient oxygen supply to the body which occurs when a person’s physical position prevents adequate breathing.” This tragic phenomenon is suspected when the autopsy of an infant reveals no discovery of a traumatic injury, when there is no pre-existing medical pathology, and when the cause of death is determined to be “Undetermined or Unknown.”
Requirements Gathering Through Focus Groups for a Real Time Emergency Communication System for HAZMAT Incidents (REACH)
Authors: Medcalf Sharon , L. Hale Matthew , Achutan Chandran , M. Yoder Aaron , Fruhling Ann , W. Shearer Stanley
Published: January 2022

During HAZMAT emergencies, first responders are the first to reach the incident site. Over the years, there has been an increase in the number of first responder deaths and heat related illness. Heat-related illnesses are most often studied in outdoor workers and wild land firefighters but occur in a variety of workers across the US. Surveillance programs reported approximately 28,000 HRI hospitalizations between 2001 and 2010. The progression from heat exhaustion to heat stroke can occur rapidly so first responders need warning systems to alert them to the impending health hazards of heat stress. This study works with HAZMAT first responders in Nebraska to explore and assess the status of responder safety in the state and begins with the first responder focus group requirements gathering process. A consensus building process was used for the focus group sessions and yielded thematic areas of health and safety concern. Responder safety was named the most common area of concern and solutions to individual risks were proposed by focus group participants from a local HAZMAT response team. The results of this focus group serve to inform researchers of priorities to consider in the development of responder health monitoring systems and to continue with research in wearable technology for real time health monitoring. Early intervention when monitored responders demonstrate signs of distress ultimately saves lives.
Kajian Penyempurnaan Kurikulum Program Studi Ilmu Komunikasi Universitas Terbuka Dari Sudut Pandang Alumni dan Pengguna Lulusan
Authors: Ida Royandiah  , Wiradharma Gunawan , Fiani Isma Dwi , Bintarti Arifah , Windrati Nila Kusuma
Published: January 2022

Program pendidikan yang ditawarkan UT harus dapat mengakomodasi tuntutan peserta didik akan kompetensi dan keterampilan yang mereka harapkan akan mereka peroleh dari proses studi mereka sesuai dengan tujuan yang telah ditetapkan program studi, serta dapat memenuhi kebutuhan pasar. Pengukuran terhadap kinerja lulusan suatu program studi dapat dilakukan melalui tracer study (penelusuran lulusan). Umpan balik yang diperoleh dari lulusan suatu program studi sangat dibutuhkan oleh perguruan tinggi untuk memperbaiki kualitas layanan dan pelaksanaan program yang diselenggarakan. Umpan balik ini juga bermanfaat pula bagi perguruan tinggi untuk memetakan dunia usaha dan industri agar jeda diantara kompetensi yang diperoleh alumni saat kuliah dengan tuntutan dunia kerja dapat diperkecil. Lokasi UPBJJ yang dijadikan sebagai lokasi penelitian terdiri atas Surakarta, Jakarta, Mataram, Banda Aceh, Malang, Yogyakarta, Bandung, Purwokerto, dan Bogor. Hasil penelitian ini memberikan informasi tentang profil kompetensi lulusan dan pengguna lulusan dari instansi-instansi. Selain itu, penelitian penelusuran lulusan dijadikan dasar untuk mengevaluasi kurikulum suatu program pendidikan untuk menunjukkan kelebihan dan kelemahan kurikulum sehingga menghasilkan saran perbaikan yang mendasar dan dikaitkan dengan kebijakan “kampus merdeka”.
Public Service Transformation during the Covid 19 Pandemic by the General Election Commission of Bandung Regency in the Local Election (Pilkada)
Authors: Sudrajat Tatang
Published: January 2022

This study aimed to elaborate the transformation of services provided by the General Election Commission of Bandung Regency during the Covid 19 pandemic to all election stakeholders in all stages of the election such as voters, political parties, administrators, candidate pairs, election supervisors, election observers, election desks and other parties. It also analysed the substance of all local elections regulations as a form of policy for the implementation of local elections during the Covid-19 pandemic. This study used qualitative method with in-depth interview and documentation. The result of this study indicated that there was a transformation of public services that relied on communication and information technology, such as updating voter data, socialization and voter education, nomination of candidate pairs, campaigning, as well as voting and counting votes.
Model Kepemimpinan di Universitas Sulawesi Barat
Authors: Syarif M
Published: January 2022

Penelitian ini bertujuan untuk menganalisis model kepemimpinan Kepala Biro Akademik dan Umum Universitas Sulawesi Barat dengan menggunakan pendekatan teori karakteristik pribadi kepemimpinan menurut Hersey dan Blanchard. Terdapat empat dimensi karakteristik pribadi pemimpin yang menjadi dasar evaluasi kepemimpinan dalam penelitian ini meliputi pengelolaan perhatian, pengelolaan makna, pengelolaan kepercayaan, dan pengelolaan diri. Pendekatan penelitian yang digunakan adalah kualitatif dengan tipe studi kasus. Data penelitian diperoleh melalui observasi langsung dan wawancara mendalam terhadap informan. Data penelitian dianailis berdasarkan prinsip pengolahan data kualitatif menggunakan model analisis data interaktif menurut Miles dan Huberman. Hasil penelitian menunjukkan bahwa karakteristik pribadi kepemimpinan Kepala Biro Akademik dan Umum Universitas Sulawesi Barat berdasarkan karakteristik pengelolaan perhatian dan karakteristik pengelolaan diri telah berjalan dengan maksimal. Tetapi pada karakteristik pengelolaan makna belum berjalan dengan maksimal disebabkan oleh kemampuan pemimpin dalam mengaplikasikan kreativitasnya kepada para pegawai atau stafnya dianggap belum berjalan dengan optimal seperti berupaya untuk menyediakan beberapa kegiatan-kegiatan pendukung kepada para pegawai untuk meningkatkan kemampuan mereka di setiap bidang. Demikian juga, pada karakteristik pengelolaan kepercayaan belum terlaksana secara optimal disebabkan oleh belum maksimalnya penerapan konsistensi dan ketepatan waktu dalam menjalankan serta melaksanakan tugas dan tanggung jawabnya.
Elever har ojämn kunskap om tekniska system
Authors: Höst Gunnar
Published: January 2022

Tekniska system finns nästan överallt i samhället, men det är ett område som innehåller utmaningar för undervisningen. I en ny studie beskriver forskare hur elevers nivåer av kunskap varierar inom olika aspekter av tekniska system. En slutsats är att det kan vara värt för lärare att satsa på områden med särskilda utmaningar, till exempel deras syften och styrning, och andra aspekter av tekniska system som inte syns.
Evaluations of Clinical Utilization of Metagenomic Next-Generation Sequencing in Adults With Fever of Unknown Origin
Authors: Fu Zhang-fan , Zhang Hao-cheng , Zhang Yi , Cui Peng , Zhou Yang , Wang Hong-yu , Lin Ke , Zhou Xian , Wu Jing , Wu Hong-long , Zhang Wen-hong , Ai Jing-wen
Published: January 2022

Introduction

The diagnosis of infection-caused fever of unknown origin (FUO) is still challenging, making it difficult for physicians to provide an early effective therapy. Therefore, a novel pathogen detection platform is needed. Metagenomic next-generation sequencing (mNGS) provides an unbiased, comprehensive technique for the sequence-based identification of pathogenic microbes, but the study of the diagnostic values of mNGS in FUO is still limited.

Methods

In a single-center retrospective cohort study, 175 FUO patients were enrolled, and clinical data were recorded and analyzed to compare mNGS with culture or traditional methods including as smears, serological tests, and nucleic acid amplification testing (NAAT) (traditional PCR, Xpert MTB/RIF, and Xpert MTB/RIF Ultra).

Results

The blood mNGS could increase the overall rate of new organisms detected in infection-caused FUO by roughly 22.9% and 19.79% in comparison to culture (22/96 vs. 0/96; OR, ∞; p = 0.000) and conventional methods (19/96 vs. 3/96; OR, 6.333; p = 0.001), respectively. Bloodstream infection was among the largest group of those identified, and the blood mNGS could have a 38% improvement in the diagnosis rate compared to culture (19/50 vs. 0/50; OR, ∞; p = 0.000) and 32.0% compared to conventional methods (16/50 vs. 3/50; OR, 5.333; p = 0.004). Among the non-blood samples in infection-caused FUO, we observed that the overall diagnostic performance of mNGS in infectious disease was better than that of conventional methods by 20% (9/45 vs. 2/45; OR, 4.5; p = 0.065), and expectedly, the use of non-blood mNGS in non-bloodstream infection increased the diagnostic rate by 26.2% (8/32 vs. 0/32; OR, ∞; p = 0.008). According to 175 patients’ clinical decision-making, we found that the use of blood mNGS as the first-line investigation could effectively increase 10.9% of diagnosis rate of FUO compared to culture, and the strategy that the mNGS of suspected parts as the second-line test could further benefit infectious patients, improving the diagnosis rate of concurrent infection by 66.7% and 12.5% in non-bloodstream infection, respectively.

Conclusion

The application of mNGS in the FUO had significantly higher diagnostic efficacy than culture or other conventional methods. In infection-caused FUO patients, application of blood mNGS as the first-line investigation and identification of samples from suspected infection sites as the second-line test could enhance the overall FUO diagnosis rate and serve as a promising optimized diagnostic protocol in the future.
Beyond GDP: Lessons for Redefining Progress in Canadian Food System Policy
Authors: Robert Naomi , Mullinix Kent
Published: January 2022

Gross Domestic Product (GDP), while initially conceived to measure economic activity, is now the most widely used indicator for societal progress and wellbeing. Its contemporary (mis)use has been documented and discussed in 'Beyond GDP' research. This mini-review brings a food systems lens to Beyond GDP research by providing an overview of the limitations of GDP as an indicator of wellbeing, and by illustrating examples of how these are embodied in Canadian food system policy. We offer a brief summary of some established and emerging areas of research dedicated to improving assessments of societal wellbeing in policy development. We highlight connections between Beyond GDP research and advocacy for food system policy reform and suggest that strengthening connections between the two areas of research and advocacy can help center societal wellbeing within food system policy research and development in Canada.
Transcriptome Analysis Reveals Key Pathways and Candidate Genes Controlling Seed Development and Size in Ricebean (Vigna umbellata)
Authors: Verma Sachin Kumar , Mittal Shikha , Gayacharan  , Wankhede Dhammaprakash Pandhari , Parida Swarup Kumar , Chattopadhyay Debasis , Prasad Geeta , Mishra Dwijesh Chandra , Joshi Dinesh Chandra , Singh Mohar , Singh Kuldeep , Singh Amit Kumar
Published: January 2022

Ricebean (Vigna umbellata) is a lesser known pulse with well-recognized potential. Recently, it has emerged as a legume with endowed nutritional potential because of high concentration of quality protein and other vital nutrients in its seeds. However, the genes and pathways involved in regulating seed development and size are not understood in this crop. In our study, we analyzed the transcriptome of two genotypes with contrasting grain size (IC426787: large seeded and IC552985: small seeded) at two different time points, namely, 5 and 10 days post-anthesis (DPA). The bold seeded genotype across the time points (B5_B10) revealed 6,928 differentially expressed genes (DEGs), whereas the small seeded genotype across the time point (S5_S10) contributed to 14,544 DEGs. We have also identified several candidate genes for seed development–related traits like seed size and 100-seed weight. On the basis of similarity search and domain analysis, some candidate genes (PHO1, cytokinin dehydrogenase, A-type cytokinin, and ARR response negative regulator) related to 100-seed weight and seed size showed downregulation in the small seeded genotype. The MapMan and KEGG analysis confirmed that auxin and cytokinin pathways varied in both the contrasting genotypes and can therefore be the regulators of the seed size and other seed development–related traits in ricebeans. A total of 51 genes encoding SCFTIR1/AFB, Aux/IAA, ARFs, E3 ubiquitin transferase enzyme, and 26S proteasome showing distinct expression dynamics in bold and small genotypes were also identified. We have also validated randomly selected SSR markers in eight accessions of the Vigna species (V. umbellata: 6; Vigna radiata: 1; and Vigna mungo: 1). Cross-species transferability pattern of ricebean–derived SSR markers was higher in V. radiata (73.08%) than V. mungo (50%). To the best of our knowledge, this is the first transcriptomic study conducted in this crop to understand the molecular basis of any trait. It would provide us a comprehensive understanding of the complex transcriptome dynamics during the seed development and gene regulatory mechanism of the seed size determination in ricebeans.
Synthesis of Fibrous Micro-nano Hierarchical Porous Cerium Dioxide Materials by the Impregnation and Thermal Decomposition Method and Its Enhanced Photocatalytic Activity
Authors: Zhang Meng , Chen Xingwang , Zu Min , Tang Yuanzheng , Liu Chengbao , Li Wanfei , Chen Feng
Published: January 2022

Fibrous micro-nano hierarchical porous cerium dioxide materials were prepared from oriental paperbush flower stems by impregnation and thermal decomposition methods. Thermogravimetric analyzer (TG, DSC), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption-desorption isothermals, temperature-programmed reduction (TPR), and UV-Vis spectrophotometer were used to characterize the thermal decomposition behavior, microstructure and photocatalytic properties of fibrous micro-nano hierarchical porous cerium dioxide materials. The results proved that the achieved products retained a fibrous morphology similar to oriental paperbush flower stems with the original biotemplate in material completely removed. The average diameter of CeO2 particles on the surface of the material is about 9 nm, and the large specific surface area is around 55.6 m2/g. UV-Vis absorption spectra showed that the fibrous micro-nano hierarchical porous cerium dioxide materials have high light absorption capacity and can respond to simulated sunlight. The effects of initial dye concentration, catalyst concentration, pH value, cycle number, and irradiation time on the photocatalytic activity of fibrous micro-nano hierarchical porous cerium dioxide materials for the photo-degradation of methylene blue under simulated solar irradiation were systematically studied. A reasonable photocatalytic mechanism is proposed based on the experimental results and theoretical analysis. This strategy can be extended to synthesize other broad bandgap semiconductor oxides with high photocatalytic activity for the photo-degradation of organic dyes under simulated solar irradiation.
Prognosis Prediction of Uveal Melanoma After Plaque Brachytherapy Based on Ultrasound With Machine Learning
Authors: Luo Jingting , Chen Yuning , Yang Yuhang , Zhang Kai , Liu Yueming , Zhao Hanqing , Dong Li , Xu Jie , Li Yang , Wei Wenbin
Published: January 2022

Introduction

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Plaque brachytherapy remains the dominant eyeball-conserving therapy for UM. Tumor regression in UM after plaque brachytherapy has been reported as a valuable prognostic factor. The present study aimed to develop an accurate machine-learning model to predict the 4-year risk of metastasis and death in UM based on ocular ultrasound data.

Material and Methods

A total of 454 patients with UM were enrolled in this retrospective, single-center study. All patients were followed up for at least 4 years after plaque brachytherapy and underwent ophthalmologic evaluations before the therapy. B-scan ultrasonography was used to measure the basal diameters and thickness of tumors preoperatively and postoperatively. Random Forest (RF) algorithm was used to construct two prediction models: whether a patient will survive for more than 4 years and whether the tumor will develop metastasis within 4 years after treatment.

Results

Our predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.708 for predicting death using only a one-time follow-up record. Including the data from two additional follow-ups increased the AUC of the model to 0.883. We attained AUCs of 0.730 and 0.846 with data from one and three-time follow-up, respectively, for predicting metastasis. The model found that the amount of postoperative follow-up data significantly improved death and metastasis prediction accuracy. Furthermore, we divided tumor treatment response into four patterns. The D(decrease)/S(stable) patterns are associated with a significantly better prognosis than the I(increase)/O(other) patterns.

Conclusions

The present study developed an RF model to predict the risk of metastasis and death from UM within 4 years based on ultrasound follow-up records following plaque brachytherapy. We intend to further validate our model in prospective datasets, enabling us to implement timely and efficient treatments.
Case Report: Membranous Nephropathy Secondary to Cobalamin C Disease
Authors: Wang Qiang , Wang Qi , Gao Yanxia , Tang Chenquan , Gao Zhaoli , Hu Zhao
Published: January 2022

Background

Mutation of MMACHC causes inherited cobalamin C disease with methylmalonic academia (MMA) and homocysteinemia. Renal complications may also be present in patients with this deficiency. However, membranous nephropathy secondary to cobalamin C disease has not been reported to date.

Case Presentation

We encountered a 17-year-old female patient with a trans-compound mutation of MMACHC who presented with membranous nephropathy, MMA, homocysteinemia, and hyperuricemia. The mutations of c.80A>G (chr1:45966084) and c.482G>A (chr1:45974520) (predicting p.Gln27Arg and p.Arg161Gln missense changes at the amino acid level) had been inherited from her father and mother, respectively. Hydroxocobalamin, betaine, and L-carnitine were administered. The patient achieved complete remission of the membranous nephropathy and resolution of the MMA, homocysteinemia, and hyperuricemia.

Conclusion

Membranous nephropathy secondary to cobalamin C disease is reversible with timely intervention.
The Median Effective Concentration (EC50) of Epidural Ropivacaine With Different Doses of Oxycodone During Limb Surgery in Elderly Patients
Authors: Xie Kai , Wang Yu-long , Teng Wen-bin , He Rui , Li Yu-hong , Huang Su-qin
Published: January 2022

Background

Oxycodone can be used both intravenously and epidurally in elderly patients because of its strong analgesic effect and more slight respiratory inhibition compared with other opioids at the same effect. In this study, we determined the median effective concentration (EC50) of epidural ropivacaine required for great saphenous vein surgery in elderly patients in order to describe its pharmacodynamic interaction with oxycodone.

Methods

One hundred forty-one elderly patients scheduled for high ligation and stripping of the great saphenous vein surgery were allocated into three groups in a randomized, double-blinded manner as follows: Q2.5 group (2.5 mg oxycodone), Q5.0 group (5.0 mg oxycodone), and C group (normal saline). Anesthesia, was achieved with epidural ropivacaine and oxycodone. The EC50 of ropivacaine for surgery with different doses of oxycodone was adjusted by using an up-and-down sequential methods with an adjacent concentration gradient at a factor of 0.9 to inhibit analgesia. Anesthesia associated adverse events and recovery, characteristics were also recorded.

Results

The EC50 of ropivacaine for the great saphenous vein surgery in elderly patients was 0.399% (95% CI, 0.371–0.430%) in the Q2.5 group, 0.396% (95% CI, 0.355–0.441%) in the Q5.0 group, and 0.487% (95% CI, 0.510–0.465%) in the C group, respectively (P < 0.05). Specially, the EC50 of ropivacaine in the Q2.5 and Q5.0 groups was lower than that in the C group (P < 0.01), But the difference between the Q2.5 group and the Q5.0 group was not significant (P > 0.05). There was no significant difference in the Bromage score from the motor block examination, heart rate (HR) or mean arterial pressure (MAP) at each observation time point after epidural administration among the three groups (P > 0.05). No serious adverse reactions occurred in any of the three groups.

Conclusion

Oxycodone combined with ropivacaine epidural anesthesia can reduce the EC50 of ropivacaine required for elderly patients undergoing the great saphenous vein surgery. There was no significant difference in anesthesia associated adverse events among the three groups. The recommended dose of oxycodone is 2.5 mg.
Natural Saccharomyces cerevisiae Strain Reveals Peculiar Genomic Traits for Starch-to-Bioethanol Production: the Design of an Amylolytic Consolidated Bioprocessing Yeast
Authors: Gronchi Nicoletta , De Bernardini Nicola , Cripwell Rosemary A. , Treu Laura , Campanaro Stefano , Basaglia Marina , Foulquié-Moreno Maria R. , Thevelein Johan M. , Van Zyl Willem H. , Favaro Lorenzo , Casella Sergio
Published: January 2022

Natural yeast with superior fermentative traits can serve as a platform for the development of recombinant strains that can be used to improve the sustainability of bioethanol production from starch. This process will benefit from a consolidated bioprocessing (CBP) approach where an engineered strain producing amylases directly converts starch into ethanol. The yeast Saccharomyces cerevisiae L20, previously selected as outperforming the benchmark yeast Ethanol Red, was here subjected to a comparative genomic investigation using a dataset of industrial S. cerevisiae strains. Along with Ethanol Red, strain L20 was then engineered for the expression of α-amylase amyA and glucoamylase glaA genes from Aspergillus tubingensis by employing two different approaches (delta integration and CRISPR/Cas9). A correlation between the number of integrated copies and the hydrolytic abilities of the recombinants was investigated. L20 demonstrated important traits for the construction of a proficient CBP yeast. Despite showing a close relatedness to commercial wine yeast and the benchmark Ethanol Red, a unique profile of gene copy number variations (CNVs) was found in L20, mainly encoding membrane transporters and secretion pathway proteins but also the fermentative metabolism. Moreover, the genome annotation disclosed seven open reading frames (ORFs) in L20 that are absent in the reference S288C genome. Genome engineering was successfully implemented for amylase production. However, with equal amylase gene copies, L20 proved its proficiency as a good enzyme secretor by exhibiting a markedly higher amylolytic activity than Ethanol Red, in compliance to the findings of the genomic exploration. The recombinant L20 dT8 exhibited the highest amylolytic activity and produced more than 4 g/L of ethanol from 2% starch in a CBP setting without the addition of supplementary enzymes. Based on the performance of this strain, an amylase/glucoamylase ratio of 1:2.5 was suggested as baseline for further improvement of the CBP ability. Overall, L20 showed important traits for the future construction of a proficient CBP yeast. As such, this work shows that natural S. cerevisiae strains can be used for the expression of foreign secreted enzymes, paving the way to strain improvement for the starch-to-bioethanol route.
The Probiotic Identity Card: A Novel “Probiogenomics” Approach to Investigate Probiotic Supplements
Authors: Lugli Gabriele Andrea , Longhi Giulia , Alessandri Giulia , Mancabelli Leonardo , Tarracchini Chiara , Fontana Federico , Turroni Francesca , Milani Christian , Di Pierro Francesco , van Sinderen Douwe , Ventura Marco
Published: January 2022

Probiotic bacteria are widely administered as dietary supplements and incorporated as active ingredients in a variety of functional foods due to their purported health-promoting features. Currently available probiotic products may have issues with regards to their formulation, such as insufficient levels of viable probiotic bacteria, complete lack of probiotic strains that are stated to be present in the product, and the presence of microbial contaminants. To avoid the distribution of such unsuitable or misleading products, we propose here a novel approach named Probiotic Identity Card (PIC), involving a combination of shotgun metagenomic sequencing and bacterial cell enumeration by flow cytometry. PIC was tested on 12 commercial probiotic supplements revealing several inconsistencies in the formulation of five such products based on their stated microbial composition and viability.
Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice
Authors: Zhu Guohua , Du Shujuan , Wang Yuyan , Huang Xixi , Hu Gaowei , Lu Xin , Li Dajin , Zhu Yizhun , Qu Di , Cai Qiliang , Liu Lu , Du Meirong
Published: January 2022

Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females’ fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8+T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice’s fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.
Effects of Docosahexanoic Acid on Gut Microbiota and Fecal Metabolites in HIV-Infected Patients With Neurocognitive Impairment: A 6-Month Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Dong Ruihua , Lin Haijiang , Ding Yingying , Chen Xiaoxiao , Shi Ruizi , Yuan Shiying , Li Jing , Zhu Bowen , Xu Xiaohui , Shen Weiwei , Wang Keran , Ding Ding , He Na
Published: January 2022

Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium, and Agathobacter, and decreased abundances of Bacteroides and Prevotella_9. Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004.
How Useful Is Endoscopic Ultrasound in Differentiating T3/T4a T Stage of Colorectal Cancer: A Prospective Study
Authors: Han Chaoqun , Tang Xuelian , Yang Ming , Zhang Kun , Liu Jun , Lin Rong , Ding Zhen
Published: January 2022

Objective

Endoscopic ultrasound (EUS) is an established method for staging of colorectal cancer. Nevertheless, prior assessments of its T stage accuracy have been limited, particularly ambiguity in assessed T3 and T4a stage. This study was to characterize the EUS image features and pay attention to distinguish T3 from T4a T stage.

Methods

A total of 638 patients who prospectively underwent colorectal EUS were recorded. The final diagnoses were compared with the concurrent or follow-up histopathology. Univariate and multivariate logistic regressions were used to assess variation in diagnostic performance with case attributes.

Results

The accuracies of EUS in classifying colorectal cancer for overall, T1, T2, T3, and T4a stages are 73.04, 62.32, 67.46, 71.26, and 83.52%, respectively. With attention to EUS image features, the lesion penetrates the entire wall and locates below the seminal vesicles or cervix is T3 stage. If the lesion locates above clearly-defined space between the anterior rectal wall and the posterior surface of the seminal vesicles or cervix, we identify as T4a stage; However, when located above seminal vesicles or cervix but on the posterior wall of the rectum, the lesion still considers as T3 stage. The tumor location and histological type are associated with inaccuracy T stage.

Conclusions

EUS provides reliable diagnostic accuracy in the colorectal cancer stage. The seminal vesicles and cervix are the important markers to predict infiltration depth for T3/T4a stage. Furthermore, the tumor location, histological type, and EUS image features for each tumor T stage should warrant attention.
The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma
Authors: Takabe Piia , Siiskonen Hanna , Rönkä Aino , Kainulainen Kirsi , Pasonen-Seppänen Sanna
Published: January 2022

The incidence of cutaneous melanoma is rapidly increasing worldwide. Cutaneous melanoma is an aggressive type of skin cancer, which originates from malignant transformation of pigment producing melanocytes. The main risk factor for melanoma is ultraviolet (UV) radiation, and thus it often arises from highly sun-exposed skin areas and is characterized by a high mutational burden. In addition to melanoma-associated mutations such as BRAF, NRAS, PTEN and cell cycle regulators, the expansion of melanoma is affected by the extracellular matrix surrounding the tumor together with immune cells. In the early phases of the disease, hyaluronan is the major matrix component in cutaneous melanoma microenvironment. It is a high-molecular weight polysaccharide involved in several physiological and pathological processes. Hyaluronan is involved in the inflammatory reactions associated with UV radiation but its role in melanomagenesis is still unclear. Although abundant hyaluronan surrounds epidermal and dermal cells in normal skin and benign nevi, its content is further elevated in dysplastic lesions and local tumors. At this stage hyaluronan matrix may act as a protective barrier against melanoma progression, or alternatively against immune cell attack. While in advanced melanoma, the content of hyaluronan decreases due to altered synthesis and degradation, and this correlates with poor prognosis. This review focuses on hyaluronan matrix in cutaneous melanoma and how the changes in hyaluronan metabolism affect the progression of melanoma.
Aldolase A and Phospholipase D1 Synergistically Resist Alkylating Agents and Radiation in Lung Cancer
Authors: Chang Yu-Chan , Chang Peter Mu-Hsin , Li Chien-Hsiu , Chan Ming-Hsien , Lee Yi-Jang , Chen Ming-Huang , Hsiao Michael
Published: January 2022

Exposure to alkylating agents and radiation may cause damage and apoptosis in cancer cells. Meanwhile, this exposure involves resistance and leads to metabolic reprogramming to benefit cancer cells. At present, the detailed mechanism is still unclear. Based on the profiles of several transcriptomes, we found that the activity of phospholipase D (PLD) and the production of specific metabolites are related to these events. Comparing several particular inhibitors, we determined that phospholipase D1 (PLD1) plays a dominant role over other PLD members. Using the existing metabolomics platform, we demonstrated that lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) are the most critical metabolites, and are highly dependent on aldolase A (ALDOA). We further demonstrated that ALDOA could modulate total PLD enzyme activity and phosphatidic acid products. Particularly after exposure to alkylating agents and radiation, the proliferation of lung cancer cells, autophagy, and DNA repair capabilities are enhanced. The above phenotypes are closely related to the performance of the ALDOA/PLD1 axis. Moreover, we found that ALDOA inhibited PLD2 activity and enzyme function through direct protein–protein interaction (PPI) with PLD2 to enhance PLD1 and additional carcinogenic features. Most importantly, the combination of ALDOA and PLD1 can be used as an independent prognostic factor and is correlated with several clinical parameters in lung cancer. These findings indicate that, based on the PPI status between ALDOA and PLD2, a combination of radiation and/or alkylating agents with regulating ALDOA-PLD1 may be considered as a new lung cancer treatment option.
CuS@BSA-NB2 Nanoparticles for HER2-Targeted Photothermal Therapy
Authors: Ying Ming , Li Qin , Wu Jingbo , Jiang Yihang , Xu Zhourui , Ma Mingze , Xu Gaixia
Published: January 2022

Breast cancer is characterized by the uncontrolled proliferation of breast epithelial cells under the action of a variety of carcinogens. Although HER2-inhibitors were currently applied for HER2-positive breast cancer patients, they didn’t work for patients with resistance to HER2-targeted anti-cancer drugs. In this work, we prepared novel CuS@BSA-NB2 nanoparticles (NPs) for breast cancer photothermal therapy (PTT). The NPs had good biocompatibility due to the Bovine Serum Albumin (BSA) encapsulating and excellent targeting to HER2 because of nanobody 2 (NB2). Under 808 nm laser irradiation, CuS@BSA-NB2 NPs had high photothermal conversion efficiency and photothermal stability. Meanwhile, we constructed a stable cell line of MDA-MB-231/HER2 with a high expression of HER2 protein. Immunofluorescence and ICP-MS assays showed that CuS@BSA-NB2 NPs can be specifically enriched and be ingested in MDA-MB-231/HER2 cells. Furthermore, CuS@BSA-NB2 NPs had shown a more significant photothermal treatment effect than CuS@BSA under certain treatment conditions for MDA-MB-231/HER2. In addition, the cytotoxicity assay demonstrated that CuS@BSA-NB2 NPs had a low toxicity for MDA-MB-231/HER2 cells. The above results suggested that CuS@BSA-NB2 NPs were great photothermal therapeutic agents to reduce the malignant proliferation of breast epithelial cells and have potential for breast cancer therapy.
Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways
Authors: Du Zhongyan , Ma Zhimei , Lai Shanglei , Ding Qinchao , Hu Ziyi , Yang Wenwen , Qian Qianyu , Zhu Linwensi , Dou Xiaobing , Li Songtao
Published: January 2022

Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atractylodes macrocephala Koidz, is known to exhibit antioxidant activity. However, its clinical benefits against drug-induced liver injury remain largely unclear.

Purpose: This study aimed at evaluating the protective effects of AO-I against APAP-induced acute liver injury.

Methods: C57BL/6 mice were administered 500 mg/kg APAP to induce hepatotoxicity. AO-Ⅰ (60 and 120 mg/kg) was intragastrically administered 2 h before APAP dosing. Liver histopathological changes, oxidative stress and hepatic inflammation markers from each group were observed.

Results: We observed that AO-I treatment significantly reversed APAP-induced liver injury, as evidenced by improved plasma alanine transaminase (ALT) level, aspartate aminotransferase (AST) and liver H&E stain. APAP treatment increased liver malondialdehyde (MDA) content and reduced catalase (CAT) and glutathione (GSH) level; however, these effects were alleviated by AO-I intervention. Moreover, AO-I treatment significantly inhibited APAP-induced activation of pro-inflammatory factors, such as IL-1β, IL-6, and TNF-α, at both the mRNA and protein levels. Mechanistic studies revealed that AO-I attenuated APAP-induced activation of TLR4, NF-κB and MAPKs (including JNK and p38).

Conclusion: AO-I mediates protective effects against APAP-induced hepatotoxicity via the TLR4/MAPKs/NF-κB pathways. Thus, AO-I is a candidate therapeutic compound for APAP-induced hepatotoxicity.
Three-Dimensional Numerical Analysis and Engineering Evaluation of Stilling Basin and Foundation Bedrock of Kala Hydropower Station, China
Authors: Xu Jianjun , Cui Zhihao , Qian Kun , Sun Xiang , Xu Jie
Published: January 2022

Kala reservoir is a large hydropower station, which will be built on the Yalong River in Sichuan Province, China. The topography and geomorphology at the project area of the hydropower station are characterized by high mountains and a deep V-shaped valley, where the engineering geological conditions are complex. The stilling basin of the Kala reservoir is planned to be built on a weak rock mass called a sericitized slate. Therefore, the safety of stilling basin structure has an important impact on the regular operation of the Kala hydropower station. To evaluate the working state of the stilling basin structure, a three-dimensional numerical model was built, including the valley, mountains and stilling basin structure. FLAC3D (A three-dimensional finite-difference simulation software) was used to simulate engineering and mechanical responses of the stilling basin structure and the foundation rock mass under various working conditions. Based on the simulation results, the structural layout of stilling basin and the rationality of sericitized slate treatment measurements were verified. It was determined that the engineering properties of the sericitized slate would generally meet the engineering requirements. However, considering that the characteristics of sericitized slate are easy to weaken with water, it was suggested to carry out necessary foundation improvement for sericitized slate to strengthen its engineering mechanical properties.
Connexin 43-Mediated Gap Junction Communication Regulates Ameloblast Differentiation via ERK1/2 Phosphorylation
Authors: Yamada Aya , Yoshizaki Keigo , Ishikawa Masaki , Saito Kan , Chiba Yuta , Fukumoto Emiko , Hino Ryoko , Hoshikawa Seira , Chiba Mitsuki , Nakamura Takashi , Iwamoto Tsutomu , Fukumoto Satoshi
Published: January 2022

Connexin 43 (Cx43) is an integral membrane protein that forms gap junction channels. These channels mediate intercellular transport and intracellular signaling to regulate organogenesis. The human disease oculodentodigital dysplasia (ODDD) is caused by mutations in Cx43 and is characterized by skeletal, ocular, and dental abnormalities including amelogenesis imperfecta. To clarify the role of Cx43 in amelogenesis, we examined the expression and function of Cx43 in tooth development. Single-cell RNA-seq analysis and immunostaining showed that Cx43 is highly expressed in pre-secretory ameloblasts, differentiated ameloblasts, and odontoblasts. Further, we investigated the pathogenic mechanisms of ODDD by analyzing Cx43-null mice. These mice developed abnormal teeth with multiple dental epithelium layers. The expression of enamel matrix proteins such as ameloblastin (Ambn), which is critical for enamel formation, was significantly reduced in Cx43-null mice. TGF-β1 induces Ambn transcription in dental epithelial cells. The induction of Ambn expression by TGF-β1 depends on the density of the cultured cells. Cell culture at low densities reduces cell–cell contact and reduces the effect of TGF-β1 on Ambn induction. When cell density was high, Ambn expression by TGF-β1 was enhanced. This induction was inhibited by the gap junction inhibitors, oleamide, and 18α-grycyrrhizic acid and was also inhibited in cells expressing Cx43 mutations (R76S and R202H). TGF-β1-mediated phosphorylation and nuclear translocation of ERK1/2, but not Smad2/3, were suppressed by gap junction inhibitors. Cx43 gap junction activity is required for TGF-β1-mediated Runx2 phosphorylation through ERK1/2, which forms complexes with Smad2/3. In addition to its gap junction activity, Cx43 may also function as a Ca2+ channel that regulates slow Ca2+ influx and ERK1/2 phosphorylation. TGF-β1 transiently increases intracellular calcium levels, and the increase in intracellular calcium over a short period was not related to the expression level of Cx43. However, long-term intracellular calcium elevation was enhanced in cells overexpressing Cx43. Our results suggest that Cx43 regulates intercellular communication through gap junction activity by modulating TGF-β1-mediated ERK signaling and enamel formation.