bluuebunny/crossref_metadata_2025 huggingface dataset:
Práticas de Gerenciamento de Projetos e PMO em hospitais: revisão integrativa da literatura
Authors: Alves André Luiz França , Silva Simone de Cassia , Nunes Marco Antonio Prado
Published: January 2022

O objetivo deste estudo é verificar o que foi desenvolvido na literatura científica mundial em práticas de gerenciamento de projetos (GP) e implantação de Escritório de Gerenciamento de projetos (EGP) em hospitais. Trata-se de uma revisão integrativa da literatura, tendo como amostra final 19 artigos; os resultados foram analisados com relação ao ano, local do estudo, boas práticas, ferramentas e desafios. Também foi feita a busca por consonância entre os achados e as funções tipológicas desenvolvidas e defendias por Hill (2008) que compõe as funções de um EGP; pode ser visto que dentre os 19 artigos selecionados, todos apresentam práticas que permeiam umas das 5 funções de HILL (2008). Desse modo, é possível concluir que a implantação de um EGP em hospitais é promissora ao ser considerado os resultados das práticas nacionais e internacionais.
Factors affecting anxiety levels of students of the Bachelor of Medicine Study Program and the Doctor's Profession, Faculty of Medicine, Udayana University Class of 2018-2020 in Undertaking the Online Lecture Learning System During the COVID-19 Pandemic
Authors: Suryanov I Putu Divanaya , Ganesha I Gde Haryo , Purnamasidhi Cokorda Agung Wahyu
Published: January 2022

Throughout the pandemic of COVID-19, medical students have been undergoing online learning, which has the potential to cause them anxiety. The study’s objective is to determine a relationship between anxiety scales and gender, year of study, resilience scale, and social support scale. This study used a cross-sectional approach with analytic observational methodology. The year of study and gender were in the biodata section, the resilience scale was calculated utilizing the Nicholson McBride Resilience Questionnaire (NMRQ), and the social support scale was calculated utilizing the Oslo Social Support Scale-3 (OSSS-3). The Beck Anxiety Inventory (BAI) was employed to evaluate anxiety scales. The data was examined utilizing univariate and bivariate methods such as Chi-square and Kendall-tau. The amount of respondents was 238 respondents who were selected by simple random sampling. The result showed significant results (p<0.05) for factors that consist of gender (r=0.183, p<0.01), year of study (r= -0.151, p<0.05), resilience (r= -0.297, p<0.01) and social support (r= -0.243,p<0.01). This research’s findings are gender, year of study, resilience, and social support all have a significant correlation with anxiety scale experienced by respondents while participating in online learning.
Amostragem do levantamento das condições de saúde bucal durante a pandemia da COVID-19: estudo metodológico
Authors: Martins Andréa Maria Eleutério de Barros Lima , Ferreira Alice Crespo , Nicolau Lara Cristina dos Santos , Lima Pablo Xavier Versiani , Maia Marina Nascimento , Silva Laiane Ferreira da , Martins Lucas Barros Lima , Martins Maria Barros Lima , Cruz Camila Gonçalves da , Rocha Thalita Caroline
Published: January 2022

Descrever a amostragem estratificada complexa probabilística por conglomerados, considerando dificuldades impostas pela pandemia da COVID-19. Realizou-se a estimativa amostral para população finita dos escolares de 5, 12 e 15 anos (5062, 5539, 5228); excluiu-se universo de 5 anos, escolas particulares e da zona rural devido a pandemia, obtendo novo universo para 12 e 15 anos (4036, 4118). Considerou-se 95% de confiança (1,96); erro amostral de 5 e 10% e taxa de não resposta de 10%; distribuição média e desvio padrão da cárie prévios; deff=1,4; prevalências de desfecho de 50%. Avaliaram-se aqueles matriculados nas escolas sorteadas que continham as idades índice de 12 e 15 anos, preconizadas pela OMS, cujas amostras inicialmente idealizadas foram respectivamente: 1347 e 2970 para distribuição média da cárie e 540 e 537 para proporções. A pandemia inviabilizou o planejamento inicial; as novas amostras foram 1271, 2696, 527 e 528, respectivamente para 12 e 15 anos. Já o número de escolares avaliados: 2193, 2084, 233 e 477. O planejamento inicialmente idealizado não foi passível de execução, foi necessária uma nova estimativa amostral com mudança na representatividade. A população de 12 anos avaliada superou a estimada, já a de 15 anos foi inferior.
Reconstruction of the severe drought events of 1875-1879 in Shanxi Province, China, based on rain and snow record data from the Qing Palace Archives
Authors: Qu Y , Wang Q , Li Z , Zhang R , Zeng J , Song Y , Yang X , Lv J
Published: January 2022

Climate change is one of the main reasons for frequent severe droughts in many areas of China. At present, there is a lack of research on the occurrence and impact of large-scale and long-lasting extreme drought events in the historical period. This study utilized the ‘Yu-Xue-Fen-Cun’ (rain and snow record) data from the Qing Palace Archives for the Qing Dynasty and records from modern meteorological stations as data sources, combined with key parameters of the study area obtained by field experiments. The improved Green-Ampt infiltration model was used to convert historical data into precipitation data, and the precipitation anomaly percentage (PA) was calculated as a meteorological drought indicator. The spatial distribution and evolution of historical extreme drought events in Shanxi Province were studied and are discussed. The results show a severe shortage of rainfall followed by severe drought events between 1875 and 1879 in Shanxi Province. The shortage level reached its peak in 1877. Extreme drought events occurred from 1875 to 1877 when the whole province was heavily drought-stricken, with annual PA values of -65%, -64%, and -70%, respectively. Reconstructing extreme historical droughts has an important practical significance in coping with drought catastrophes that may occur now or in the future and contributes to the development of disaster prevention and preparedness strategies, disaster reduction policies, and risk prevention and control.
Functional thermal limits are determined by rate of warming during simulated marine heatwaves
Authors: De Leij R , Grange LJ , Peck LS
Published: January 2022

Marine heatwaves (MHWs) are increasing in both intensity and frequency against a backdrop of gradual warming associated with climate change. In the context of MHWs, animals are likely to experience sub-lethal rather than lethal effects, defining long-term limits to survival and/or impacting individual and population fitness. We investigated how functional sub-lethal limits track critical thresholds and how this relationship changes with warming rate. To this end, we monitored basic functioning, specifically the ability to right, feed and assimilate energy, as well as oxygen consumption rate in the common Antarctic sea urchin Sterechinus neumayeri. Water temperature in experimental systems was increased at rates of 1, 0.5 and 0.3°C d-1, in line with the characteristics of MHW events previously experienced at the site where the study urchins were collected on the Antarctica Peninsula. Functioning was assessed during the simulation of MHWs, and sub-lethal limits were determined when the rate of functional degradation changed as temperature increased. Results suggest that thermal sensitivity varies between the key biological functions measured, with the ability to right having the highest thermal threshold. Functions deteriorated at lower temperatures when warming was more rapid (1°C d-1), contrary to lethal critical thresholds, which were reached at lower temperatures when warming was slower (0.3°C d-1). MHWs and their impacts extend far beyond Antarctica, and in this context, our analyses indicate that the onset rate of MHWs is critical in determining the ability of an organism to tolerate short-term elevated temperatures.
PEMANFAATAN APLIKASI ONLINE DALAM PEMBELAJARAN JARAK JAUH DAN DAMPAKNYA TERHADAP PENCAPAIAN KOMPETENSI MULTIMEDIA DI SMKN 1 KOTA JAMBI
Authors: A Ardiansyah. , Sofyan Sofyan , Harjono Hary Soedarto
Published: January 2022

This study aims to explain the use of online applications in distance learning and its impact on the achievement of multimedia competencies at SMKN 1 Jambi City. This study uses a qualitative method with phenomenological research. For data collection conducted, interviews and documentation. To analyze the data consists of three activity lines simultaneously, namely data reduction, data presentation, and drawing conclusions.The results of observing can be concluded in class X-1 and X-2 are able to adapt using online applications in online learning. Meanwhile, grades XII-1, XII-2, and XII-3 have gotten used to online applications provided by schools in online learning. Furthermore, the results of interviews from 10 informants and 15 questions became the basis for in-depth data sources on the phenomena that occurred based on experts that distance learning was learning independently by utilizing online applications as a medium in honing skills and communication tools online learning.
ANALISIS PENCAPAIAN KOMPETENSI KEAHLIAN TATA BOGA SISWA KELAS XI SMKN 4 KOTA JAMBI MELALUI PEMBELAJARAN JARAK JAUH
Authors: Sistranafya Iky , Sofyan Sofyan , Nazurty Nazurty
Published: January 2022

The purpose of this study to describe implementation of prakerin, achievement of students on the competence of Tata Boga in PJJ SMKN 4 Jambi City. Research method used is qualitative through phenomenological research with purposive sampling techniques, instruments used, namely observation, interview and data analysis refer to Miles and Huberman's theory. The results of observation obtained implementation of prakerin during covid-19 pandemic was not carried out for a full 6 months, but implementation of prakerin was carried out for 2 (two) months in DU/DI. The results of interview were obtained after carrying out prakerin, students gained new experience in the field of food and beverage processing, and knew the stages of food and beverage processing both about cookie dough, texture of cake dough and so on, new knowledge and experience in the industrial world and in the business world. Students use online applications and mobile media tools during PJJ to achieve competency skills tata boga.
PEMANFAATAN APLIKASI GOOGLE MEET SEBAGAI MEDIA PELAKSANAAN LAYANAN BIMBINGAN KLASIKAL SISWA SMAN 12 KOTA JAMBI
Authors: Gusdarti Desi , Harjono Hary Soedarto , Haryanto Eddy
Published: January 2022

The purpose of this study is to find out how to use the Google Meet application in the implementation of classical guidance services in students of class XII SMAN 12 Jambi City. This research method is a qualitative research method that uses purposive sampling techniques in data collection using unstructured interviews and triangulation, after which it is analyzed using qualitative descriptive to get an idea of the facts. The results of the study conducted by researchers through interviews with 5 informants about the use of google meet application as a medium of implementation of classical guidance services for students of class XII SMAN 12 Jambi City showed that the google meet application is the right choice to be used as a medium of implementation of classical guidance services because it meets the five principles of learning media, namely effectiveness, relevance, efficiency, usable and contextual.
Proses Perubahan Diri Seorang Teroris menjadi Aktivis Perdamaian
Authors: Syafiq Muhammad
Published: January 2022

This qualitative study was aimed at exploring  the  experience  of  a former  member of a terrorist organization in Indonesia who  have  left  his terrorist group and abandoned the extremist ideology. A life history method which focuses on the process of self-change and life transition of the former member of the terrorist group was employed A participant whose age is 40 years old and was a former active member of Jamaah Islamiyah (JI), a terrorist group, was recruited. He was captured in 2014 and served a sentence in prison for almost 4 years. He has been involved in counter-terrorism campaign organized by a non-government organization (NGO) since his release from prison until recently. Interviews were conducted to collect data which were then analyzed using a narrative analysis. Some written documents in the forms of articles and a published book produced by the participant as well as online news covering the participant’ stories were also examined. The findings inform how he became involved in the terrorist networks. The need for self-significance and adventurous experience seems to be the main drivers. After his capture, and during his imprisonment, he contemplated his participation in the terrorist networks. His meetings with religious experts and academicians facilitated by prison officers, and his awareness of burden he had inflicted on his family because of his terrorism case had opened his mind. He experienced a turning life moment which made him keeping distance from other terrorist inmates with the risk of receiving negative view from them. After his release, he found passion in writing and eventually reached a NGO and joined it as a credible voice in the campaigns of counter violent extremism through writing and public speaking.
TINGKAT BEBAN KERJA MENTAL KARYAWAN PADA LAYANAN BUSINESS, GOVERNMENT, ENTERPRISE (BGES) BOGOR PT. TELKOM INDONESIA BERDASARKAN METODE NASA-TLX
Authors: Zuraida Rida , Aprillia Monika Nadya
Published: January 2022

PT. Telkom Indonesia merupakan salah satu penyelenggara layanan telepon dan internet di Indonesia. Masih terdapat banyak sekolah yang belum memiliki fasilitas internet, sehingga PT. Telkom melakukan edukasi dan penawaran fasillitas ini. PT. Telkom di Bogor yaitu divisi BGES (Business, Government, Enterprise) merupakan divisi yang menawarkan layanan ini. Banyaknya jumlah sekolah yang belum memiliki fasilitas internet di Bogor serta luasnya area layanan, mendorong penelitian mengenai beban kerja mental karyawan di divisi ini. Penilaian beban kerja dilakukan pada 12 karyawan di bagian Account  Manager (AM) Government, AM Pro, dan AM organik menggunakan metoda NASA-TLX. Hasilnya adalah beban kerja pada ketiga bagian AM tersebut dikategorikan tinggi. Dari lima dimensi beban kerja mental, hanya Physical Demand (PD) yang dikategorikan sedang, sisanya yaitu Mental Demand (MD), Temporal Demand (TD), Performance (P), Frustration level (FR) dikategorikan tinggi. Penambahan karyawan, pengaturan jadwal visit ke konsumen, dan keluar kota dapat dilakukan untuk menyeimbangkan beban kerja yang dirasakan karyawan saat ini.
Aplikasi Metode American Productivity Center (APC) Dan Analisis Fishbone diagram Untuk Meningkatkan Produktivitas
Authors: Rusady Evelyn
Published: January 2022

UKM Kerupuk Acoy is a small and medium business engaged in the production of kerupuk and kemplang which has been established since 2012. After conducting interviews it was found that there were internal problems caused by a decrease in productivity, namely the use of resources that were not yet efficient so that although there was an increase in sales but the benefits are not maximized. To overcome this, it is necessary to apply the APC method to see which inputs have an index below 100% so that improvements are needed to increase productivity. The results of data processing showed a decrease in productivity levels material, energy, and capital inputs. Using fishbone diagram analysis, the root cause of the problem was found, namely low material productivity due to waste of raw materials for flour and cooking oil as well as too dense kerupuk dough form and making kemplang dough rolls too large, low energy productivity due to gas waste due to infrequent cleaning of stove fires, and low productivity. capital because the amount of working capital used is not proportional to the output produced. The solutions to increase productivity that have been implemented are cleaning the stove fire after use, reducing working capital, reducing the size of the cracker print and the diameter of the kemplang rolls, and paying attention to the use of flour and cooking oil so as not to spill on the floor. After implementation, there was an increase in the productivity of material, energy, and capital inputs respectively by 6.28252%; 6.28278%; and 0.05713% which causes an increase in output productivity of 6.283%.
The Effect of Catalyst Amount & Reacters Comperative on Glycerol Conversion From Castrol Oil With Catalyst Of Pertamina Cracking Process Unit III Palembang
Authors: Roni Kiagus Ahmad
Published: January 2022

Transesterification of oil with alcohol produces glycerol and methyl esters (biodiesel). The reaction is influenced, among others, by the amount of catalyst and the ratio of oil and meth hanol reagents. This purpose of research to determine the effect of the amount of catalyst and the ratio of reagents on the conversion of glycerol. The experiment was carried out in a three-necked flask equipped with a stirrer and reverse cooling. In a three-necked flask, 150 ml of castor oil was added, 0.375 ml of H2SO4 was added, heated to a temperature of 650C. Then add 185 ml of methanol and stir for 30 minutes. Then let stand 24 hours to form two layers. The bottom layer is glycerol. The transesterification process was continued by adding 100 ml of glycerol in a mixture of methanol (variation 1:2, 1:3, 1:4) with RCC catalyst (variation 1.7gr;1.9gr;2.1gr;2.3gr ;2.5gr) The mixture was then stirred at 90 rpm for 75 minutes. Based on the results of research conducted, the highest glycerol conversion value was in the amount of catalyst 2.1 g with a ratio of reagents between castor oil and methanol of 1:3 of 55.33%.
Performa Motor Induksi Satu Phasa Sebagai Penggerak Mesin Pengering
Authors: Muhammad Mukhlis , Yuniarti Erliza , Sofiah Sofiah , Saputra Aldo , Pani Adi
Published: January 2022

Utilization of an induction motor as a driving force for an oil drying machine because of its strong construction and easy maintenance. The dryer is designed to use a tube made of aluminum with an iron frame equipped with a dimmer as a voltage regulator and a timer for setting the drying time. The engine performance test was carried out with a voltage variation of 80-100 Volts with a time of 30-240 seconds with a constant load weight. Based on the research, the performance of the dryer was obtained, at a voltage of 90-100 Volts, the engine speed was stable at 2500 rpm in a drying time of 90-120 seconds. The decrease in load in the drying process can increase the rotation of the motor, otherwise the motor torque will be smaller with the increase in motor rotation and the length of the drying process.
Treatment of medulloblastoma in pediatric patients over 3 years old: modern approaches with respect to molecular and biologic tumor features
Authors: Zagidullina S. R. , Levashov A. S. , Grigorenko V. A. , Valiev T. T.
Published: January 2022

Medulloblastoma (MB) treatment in pediatric patients is an open challenge in clinical oncology. Current treatment protocols are risk-adopted and risk group criteria continuously evolve by increasing data about molecular and biologic mechanisms of MB tumorogenesis. In the current issue it is reviewed modern treatment programs, which became a basis of Russian and International clinical recommendations. It is analyzed treatment results according to regimens of chemotherapy and irradiation, absence or presence of metastases, histologic variant and molecular and biologic tumor features.
INOVASI PELAYANAN PAJAK KENDARAAN BERMOTOR DALAM MENINGKATKAN KUALITAS PELAYANAN PUBLIK PADA KANTOR SAMSAT DI KABUPATEN PANDEGLANG
Authors: Defrian Diki , Sururi Ahmad , Hasanah Budi
Published: January 2022

Kompleksitas permasalahan seperti antrian yang menumpuk, pungutan liar, praktek calo dan masih kurangnya kemauan serta kesadaraan masyarakat dalam membayar pajak kendaraan bermotor merupakan beberapa permasalahan yang harus dihadapi oleh UPT Samsat Kabupaten Pandeglang. Tujuan penelitian ini adalah untuk mendiskusikan inovasi pelayanan pajak kendaraan bermotor dalam meningkatkan kualitas pelayanan publik di Samsat Kabupaten Pandeglang. Metode penelitian ini menggunakan jenis  deskriptif dengan pendekatan kualitatif. Adapun teknik pengumpulan datanya berupa observasi, wawancara dan dokumentasi serta teknik analisis data meliputi reduksi, verifikasi dan kesimpulan. Hasil penelitian menunjukan bahwa inovasi pelayanan pajak kendaraan bermotor di Samsat Kabupaten Pandeglang dalam pelaksanaannya sudah berjalan dengan baik, meskipun masih perlu untuk terus mendorong inovasi pelayanan yang lebih intensif pada indikator kesesuaian dan kerumitan. 

Kata kunci : Inovasi, Pelayanan Publik,  Pajak Kendaraan, Pandeglang.
Ebla Tabletleri Eski Ahit'in Tarihselliğini Destekliyormu?
Authors: DOĞAN Servet
Published: January 2022

MÖ 2400-1600 yılları arasında tarihlene Ebla Uygarlığı'na ait tabletler 1975 yılında Suriye’nin Tel Mardik bölgesinde bulundu. Bu tabletlerin içeriği daha önce Mısır ve Mezopotamya metinleri üzerinden oluşan kannatlerle örtüşmüyordu. Ebla Mısır ve Mezepotamya gibi büyük bir akarsuyun etrafında değil küçük akarsularının ve yağmur sularının kontrol altına alınarak tarım yapılan bir bölgede gelişmişti. Bir grup arkeolog Ebla Uygarlığına ait olan bu tabletlerin patriarklar dönemine ait olduğunu ve Patriark isimleri de dâhil olmak üzere Eski Ahit anlatılarıyla bir dizi paralellikler taşıdığını iddia etmişlerken diğer bir grup tabletlerde Eski Ahit anlatılarını destekleyecek her hangi bir şeyin olmadığını savunmuştur. Bazıları da Ebla Uygarlığına ait inançların Eski Ahit’teki bazı inançların kaynağını oluşturduğunu ispatlamaya çalışmıştır. Ebla tabletlerinden üç ayrı grup kendilerini destekleyecek deliller aramaktadır. Benzer şekilde Ebla dilinin Eski Kenan dili, Akadcanın bir lehçesi ya da müstakil bir dil olduğu yolunda görüşler ortaya atılmıştırEbla tabletlerinin Kitabı Mukaddes arkeolojisini ya da Pan-Babilonist benzeri yaklaşımları destekleyecek malzemeler içermediği anlaşılmaktadır. Bununla birlikte uzun zaman önce kaybolmuş bir Sami dilinin keşfinin ilerde yapılacak çalışmalarla Kitabı Mukaddes Araştırmaları, eski uygarlıklar ve Sami dilleri çalışmalarına katkıda bulunacağı söylenebilir.
Therapeutic Validation of Venous Pulsatile Tinnitus and Biomaterial Applications for Temporal Bone Reconstruction Surgery Using Multi-sensing Platforms and Coupled Computational Techniques
Authors: Hsieh Yue-Lin , Gao Xiuli , Wang Xing , Hsiang Fu-Chou , Sun Xinbo , Wang Wuqing
Published: January 2022

The application of grafts and biomaterials is a cardinal therapeutic procedure to resolve venous pulsatile tinnitus (PT) caused by temporal bone dehiscence during transtemporal reconstructive surgery. However, the transmission mechanism of venous PT remains unclear, and the sound absorption and insulation properties of different repair materials have not been specified. This study quantifies the vibroacoustic characteristics of PT, sources the major transmission pathway of PT, and verifies the therapeutic effect of different material applications using joint multi-sensing platforms and coupled computational fluid dynamics (CFD) techniques. The in vivo intraoperative acoustic and vibroacoustic characteristics of intrasinus blood flow motion and dehiscent sigmoid plate of a typical venous PT patient were investigated using acoustic and displacement sensors. The acoustical, morphological, and mechanical properties of the dehiscent sigmoid plate, grafts harvested from a cadaveric head, and other biomaterials were acquired using acoustical impedance tubes, micro-CT, scanning electron microscopy, and mercury porosimetry, as appropriate. To analyze the therapeutic effect of our previous reconstructive techniques, coupled CFD simulations were performed using the acquired mechanical properties of biomaterials and patient-specific radiologic data. The peak in vivo intraoperatively gauged, peak simulated vibroacoustic and peak simulated hydroacoustic amplitude of PT prior to sigmoid plate reconstruction were 64.0, 70.4, and 72.8 dB, respectively. After the solidified gelatin sponge–bone wax repair technique, the intraoperative gauged peak amplitude of PT was reduced from 64.0 to 47.3 dB. Among three different reconstructive techniques based on CFD results, the vibroacoustic and hydroacoustic sounds were reduced to 65.9 and 68.6 dB (temporalis–cartilage technique), 63.5 and 63.1 dB (solidified gelatin sponge technique), and 42.4 and 39.2 dB (solidified gelatin sponge–bone wax technique). In conclusion, the current novel biosensing applications and coupled CFD techniques indicate that the sensation of PT correlates with the motion and impact from venous flow, causing vibroacoustic and hydroacoustic sources that transmit via the air-conduction transmission pathway. The transtemporal reconstructive surgical efficacy depends on the established areal density of applied grafts and/or biomaterials, in which the total transmission loss of PT should surpass the amplitude of the measured loudness of PT.
Engineering of CYP153A33 With Enhanced Ratio of Hydroxylation to Overoxidation Activity in Whole-Cell Biotransformation of Medium-Chain 1-Alkanols
Authors: Park Hyuna , Bak Doyeong , Jeon Wooyoung , Jang Minjung , Ahn Jung-Oh , Choi Kwon-Young
Published: January 2022

α,ω-Dodecanediol is a versatile material that has been widely used not only as an adhesive and crosslinking reagent, but also as a building block in the pharmaceutical and polymer industries. The biosynthesis of α,ω-dodecanediol from fatty derivatives, such as dodecane and dodecanol, requires an ω-specific hydroxylation step using monooxygenase enzymes. An issue with the whole-cell biotransformation of 1-dodecanol using cytochrome P450 monooxygenase (CYP) with ω-specific hydroxylation activity was the low conversion and production of the over-oxidized product of dodecanoic acid. In this study, CYP153A33 from Marinobacter aquaeolei was engineered to obtain higher ω-specific hydroxylation activity through site-directed mutagenesis. The target residue was mutated to increase flux toward α,ω-dodecanediol synthesis, while reducing the generation of the overoxidation product of dodecanoic acid and α,ω-dodecanedioic acid. Among the evaluated variants, CYP153A33 P136A showed a significant increase in 1-dodecanol conversion, i.e., 71.2% (7.12 mM from 10 mM 1-dodecanol), with an increased hydroxylation to over-oxidation activity ratio, i.e., 32.4. Finally, the applicability of this engineered enzyme for ω-specific hydroxylation against several 1-alkanols, i.e., from C6 to C16, was investigated and discussed based on the structure-activity relationship.
Advancement in Cancer Stem Cell Biology and Precision Medicine—Review Article Head and Neck Cancer Stem Cell Plasticity and the Tumor Microenvironment
Authors: Heft Neal Molly E. , Brenner J. Chad , Prince Mark E. P. , Chinn Steven B.
Published: January 2022

Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor heterogeneity, treatment resistance, metastasis, and recurrence in solid malignancies including head and neck cancer. Initial studies identified cancer stem cell markers including CD44 and ALDH in head and neck malignancies and found that these cells show aggressive features in both in vitro and in vivo studies. Recent evidence has now revealed a key role of the tumor microenvironment in maintaining a cancer stem cell niche and promoting cancer stem cell plasticity. There is an increasing focus on identifying and targeting the crosstalk between cancer stem cells and surrounding cells within the tumor microenvironment (TME) as new therapeutic potential, however understanding how CSC maintain a stem-like state is critical to understanding how to therapeutically alter their function. Here we review the current evidence for cancer stem cell plasticity and discuss how interactions with the TME promote the cancer stem cell niche, increase tumor heterogeneity, and play a role in treatment resistance.
The Regulation of Growth in Developing, Homeostatic, and Regenerating Tetrapod Limbs: A Minireview
Authors: Wells Kaylee M. , Baumel Mary , McCusker Catherine D.
Published: January 2022

The size and shape of the tetrapod limb play central roles in their functionality and the overall physiology of the organism. In this minireview we will discuss observations on mutant animal models and humans, which show that the growth and final size of the limb is most impacted by factors that regulate either limb bud patterning or the elongation of the long bones. We will also apply the lessons that have been learned from embryos to how growth could be regulated in regenerating limb structures and outline the challenges that are unique to regenerating animals.
Identification of Breast Cancer Immune Subtypes by Analyzing Bulk Tumor and Single Cell Transcriptomes
Authors: Yao Jia , Li Shengwei , Wang Xiaosheng
Published: January 2022

Background: The histological and molecular classification of breast cancer (BC) is being used in the clinical management of this disease. However, subtyping of BC based on the tumor immune microenvironment (TIME) remains insufficiently explored, although such investigation may provide new insights into intratumor heterogeneity in BC and potential clinical implications for BC immunotherapy.

Methods: Based on the enrichment scores of 28 immune cell types, we performed clustering analysis of transcriptomic data to identify immune-specific subtypes of BC using six different datasets, including five bulk tumor datasets and one single-cell dataset. We further analyzed the molecular and clinical features of these subtypes.

Results: Consistently in the six datasets, we identified three BC subtypes: BC-ImH, BC-ImM, and BC-ImL, which had high, medium, and low immune signature scores, respectively. BC-ImH displayed a significantly better survival prognosis than BC-ImL. Triple-negative BC (TNBC) and human epidermal growth factor receptor-2-positive (HER2+) BC were likely to have the highest proportion in BC-ImH and the lowest proportion in BC-ImL. In contrast, hormone receptor-positive (HR+) BC had the highest proportion in BC-ImL and the lowest proportion in BC-ImH. Furthermore, BC-ImH had the highest tumor mutation burden (TMB) and predicted neoantigens, while BC-ImL had the highest somatic copy number alteration (SCNA) scores. It is consistent with that TMB and SCNA correlate positively and negatively with anti-tumor immune response, respectively. TP53 had the highest mutation rate in BC-ImH and the lowest mutation rate in BC-ImL, supporting that TP53 mutations promote anti-tumor immune response in BC. In contrast, PIK3CA displayed the highest mutation rate in BC-ImM, while GATA3 had the highest mutation rate in BC-ImL. Besides immune pathways, many oncogenic pathways were upregulated in BC-ImH, including ErbB, MAPK, VEGF, and Wnt signaling pathways; the activities of these pathways correlated positively with immune signature scores in BC.

Conclusions: The tumors with the strong immune response (“hot” tumors) have better clinical outcomes than the tumors with the weak immune response (“cold” tumors) in BC. TNBC and HER2+ BC are more immunogenic, while HR + BC is less immunogenic. Certain HER2+ or HR + BC patients could be propitious to immunotherapy in addition to TNBC.
Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation
Authors: Gao Qianmin , Wang Lipeng , Wang Sicheng , Huang Biaotong , Jing Yingying , Su Jiacan
Published: January 2022

Bone marrow mesenchymal stromal cells (BMSCs), identified as pericytes comprising the hematopoietic niche, are a group of heterogeneous cells composed of multipotent stem cells, including osteochondral and adipocyte progenitors. Nevertheless, the identification and classification are still controversial, which limits their application. In recent years, by lineage tracing and single-cell sequencing, several new subgroups of BMSCs and their roles in normal physiological and pathological conditions have been clarified. Key regulators and mechanisms controlling the fate of BMSCs are being revealed. Cross-talk among subgroups of bone marrow mesenchymal cells has been demonstrated. In this review, we focus on recent advances in the identification and classification of BMSCs, which provides important implications for clinical applications.
Altered BMP2/4 Signaling in Stem Cells and Their Niche: Different Cancers but Similar Mechanisms, the Example of Myeloid Leukemia and Breast Cancer
Authors: Guyot Boris , Lefort Sylvain , Voeltzel Thibault , Pécheur Eve-Isabelle , Maguer-Satta Véronique
Published: January 2022

Understanding mechanisms of cancer development is mandatory for disease prevention and management. In healthy tissue, the microenvironment or niche governs stem cell fate by regulating the availability of soluble molecules, cell-cell contacts, cell-matrix interactions, and physical constraints. Gaining insight into the biology of the stem cell microenvironment is of utmost importance, since it plays a role at all stages of tumorigenesis, from (stem) cell transformation to tumor escape. In this context, BMPs (Bone Morphogenetic Proteins), are key mediators of stem cell regulation in both embryonic and adult organs such as hematopoietic, neural and epithelial tissues. BMPs directly regulate the niche and stem cells residing within. Among them, BMP2 and BMP4 emerged as master regulators of normal and tumorigenic processes. Recently, a number of studies unraveled important mechanisms that sustain cell transformation related to dysregulations of the BMP pathway in stem cells and their niche (including exposure to pollutants such as bisphenols). Furthermore, a direct link between BMP2/BMP4 binding to BMP type 1 receptors and the emergence and expansion of cancer stem cells was unveiled. In addition, a chronic exposure of normal stem cells to abnormal BMP signals contributes to the emergence of cancer stem cells, or to disease progression independently of the initial transforming event. In this review, we will illustrate how the regulation of stem cells and their microenvironment becomes dysfunctional in cancer via the hijacking of BMP signaling with main examples in myeloid leukemia and breast cancers.
Bridging the Gap: Connecting the Mechanisms of Immune-Related Adverse Events and Autoimmunity Through PD-1
Authors: Mor Adam , Strazza Marianne
Published: January 2022

The emergence of anti–cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), anti–programmed cell death 1 ligand (anti–PD-1), and anti–PD-L1 antibodies as immune checkpoint inhibitors (ICIs) revolutionized the treatment of numerous types of tumors. These antibodies, both alone and in combination, provide great clinical efficacy as evidenced by tumor regression and increased overall patients’ survival. However, with this success comes multiple challenges. First, while patients who respond to ICIs have outstanding outcomes, there remains a large proportion of patients who do not respond at all. This all-or-none response has led to looking downstream of programmed cell death 1 (PD-1) for additional therapeutic targets and for new combination therapies. Second, a majority of patients who receive ICIs go on to develop immune-related adverse events (irAEs) characterized by end-organ inflammation with T-cell infiltrates. The hallmarks of these clinically observed irAEs share many similarities with primary autoimmune diseases. The contribution of PD-1 to peripheral tolerance is a major mechanism for protection against expansion of self-reactive T-cell clones and autoimmune disease. In this review, we aim to bridge the gaps between our cellular and molecular knowledge of PD-1 signaling in T cells, ICI-induced irAEs, and autoimmune diseases. We will highlight shared mechanisms and the potential for new therapeutic strategies.
Differential Expression Profiles and Potential Intergenerational Functions of tRNA-Derived Small RNAs in Mice After Cadmium Exposure
Authors: Zeng Ling , Zhou Jinzhao , Zhang Yanwei , Wang Xiaofei , Wang Mei , Su Ping
Published: January 2022

Cadmium (Cd) is a toxic heavy metal and ubiquitous environmental endocrine disruptor. Previous studies on Cd-induced damage to male fertility mainly focus on the structure and function of testis, including cytoskeleton, blood-testis barrier, and steroidogenesis. Nevertheless, to date, no studies have investigated the effects of Cd exposure on sperm epigenetic inheritance and intergenerational inheritance. In our study, we systematically revealed the changes in sperm tRNA-derived small RNAs (tsRNA) profiles and found that 14 tsRNAs (9 up-regulated and 5 down-regulated) were significantly altered after Cd exposure. Bioinformatics of tsRNA-mRNA-pathway interactions revealed that the altered biological functions mainly were related to ion transmembrane transport, lipid metabolism and cell membrane system. In addition, we focused on two stages of early embryo development and selected two organs to study the impact of these changes on cell membrane system, especially mitochondrion and lysosome, two typical membrane-enclosed organelles. Surprisingly, we found that the content of mitochondrion was significantly decreased in 2-cell stage, whereas remarkably increased in the morula stage. The contents of mitochondrion and lysosome were increased in the testes of 6-day-old offspring and livers of adult offspring, whereas remarkably decreased in the testes of adult offspring. This provides a possible basis to further explore the effects of paternal Cd exposure on offspring health.
SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer
Authors: Wang Hao , Yin Jinwen , Hong Yuntian , Ren Anli , Wang Haizhou , Li Mengting , Zhao Qiu , Jiang Congqing , Liu Lan
Published: January 2022

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.
Long Non-Coding RNAs in Lung Cancer: The Role in Tumor Microenvironment
Authors: Dai Shuang , Liu Ting , Liu Yan-Yang , He Yingying , Liu Tao , Xu Zihan , Wang Zhi-Wu , Luo Feng
Published: January 2022

The development of various therapeutic interventions, particularly immune checkpoint inhibitor therapy, have effectively induced tumor remission for patients with advanced lung cancer. However, few cancer patients can obtain significant and long-lasting therapeutic effects for the limitation of immunological nonresponse and resistance. For this case, it’s urgent to identify new biomarkers and develop therapeutic targets for future immunotherapy. Over the past decades, tumor microenvironment (TME)-related long non-coding RNAs (lncRNAs) have gradually become well known to us. A large number of existing studies have indicated that TME-related lncRNAs are one of the major factors to realize precise diagnosis and treatment of lung cancer. Herein, this paper discusses the roles of lncRNAs in TME, and the potential application of lncRNAs as biomarkers or therapeutic targets for immunotherapy in lung cancer.
An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models
Authors: Hines Timothy J. , Lutz Cathleen , Murray Stephen A. , Burgess Robert W.
Published: January 2022

As sequencing technology improves, the identification of new disease-associated genes and new alleles of known genes is rapidly increasing our understanding of the genetic underpinnings of rare diseases, including neuromuscular diseases. However, precisely because these disorders are rare and often heterogeneous, they are difficult to study in patient populations. In parallel, our ability to engineer the genomes of model organisms, such as mice or rats, has gotten increasingly efficient through techniques such as CRISPR/Cas9 genome editing, allowing the creation of precision human disease models. Such in vivo model systems provide an efficient means for exploring disease mechanisms and identifying therapeutic strategies. Furthermore, animal models provide a platform for preclinical studies to test the efficacy of those strategies. Determining whether the same mechanisms are involved in the human disease and confirming relevant parameters for treatment ideally involves a human experimental system. One system currently being used is induced pluripotent stem cells (iPSCs), which can then be differentiated into the relevant cell type(s) for in vitro confirmation of disease mechanisms and variables such as target engagement. Here we provide a demonstration of these approaches using the example of tRNA-synthetase-associated inherited peripheral neuropathies, rare forms of Charcot-Marie-Tooth disease (CMT). Mouse models have led to a better understanding of both the genetic and cellular mechanisms underlying the disease. To determine if the mechanisms are similar in human cells, we will use genetically engineered iPSC-based models. This will allow comparisons of different CMT-associated GARS alleles in the same genetic background, reducing the variability found between patient samples and simplifying the availability of cell-based models for a rare disease. The necessity of integrating mouse and human models, strategies for accomplishing this integration, and the challenges of doing it at scale are discussed using recently published work detailing the cellular mechanisms underlying GARS-associated CMT as a framework.
The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway
Authors: Qi Wenwen , Zhu Fangyuan , Wang Min , Teng Zhenxiao , Xu Runtong , Xi Yue , Meng Qiu , Wu Xinhao , Zhao Hui , Ma Min , Hou Xiaozhi , Wang Baowei , Li Xiaoming , Liu Chengcheng , Zhang Xiang , Xu Fenglei , Xia Ming
Published: January 2022

Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.
Autophagy of the Nucleus in Health and Disease
Authors: Konstantinidis Georgios , Tavernarakis Nektarios
Published: January 2022

Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typically excluded during conventional macronucleophagy and micronucleophagy, indicating that degradation of nuclear cargo is tightly regulated. In mammals, similarly to other autophagy subtypes, nucleophagy is crucial for cellular differentiation and development, in addition to enabling cells to respond to various nuclear insults and cell cycle perturbations. A common denominator of all nucleophagic processes characterized in diverse organisms is the dependence on the core autophagic machinery. Here, we survey recent studies investigating the autophagic processing of nuclear components. We discuss nucleophagic events in the context of pathology, such as neurodegeneration, cancer, DNA damage, and ageing.
Lateral Flow Assay for the Detection of African Swine Fever Virus Antibodies Using Gold Nanoparticle-Labeled Acid-Treated p72
Authors: Zhu Wenzhuang , Meng Kaiwen , Zhang Yueping , Bu Zhigao , Zhao Dongming , Meng Geng
Published: January 2022

African swine fever is a widespread and highly contagious disease in the porcine population, which is caused by African swine fever virus (ASFV). The PCR and ELISA detection methods are the main conventional diagnostic methods for ASFV antigen/antibody detection in the field. However, these methods have limitations of expensive equipment, trained technicians, and time-consuming results. Thus, a rapid, inexpensive, accurate and on-site detection method is urgently needed. Here we describe a double-antigen-sandwich lateral-flow assay based on gold nanoparticle-conjugated ASFV major capsid protein p72, which can detect ASFV antibody in serum samples with high sensitivity and specificity in 10 min and the results can be determined by naked eyes. A lateral flow assay was established by using yeast-expressed and acid-treated ASFV p72 conjugated with gold nanoparticles, which are synthesized by seeding method. A high coincidence (97.8%) of the assay was determined using clinical serum compared to a commercial ELISA kit. In addition, our lateral flow strip can detect as far as 1:10,000 diluted clinically positive serum for demonstration of high sensitivity. In summary, the assay developed here was shown to be rapid, inexpensive, accurate and highly selective. It represents a reliable method for on-site ASFV antibody detection and may help to control the ASFV pandemic.