bluuebunny/crossref_metadata_2025 huggingface dataset:
Nozzle resonance mechanism and cooperative optimization of self-excited oscillating pulse cavitation jet
Authors: Yuan Xiaoming , Wang Ning , Wang Weidong , Zhang Lijie , Zhu Yong
Published: October 2022

The peak value and pulsation amplitude of the self-excited oscillating pulse cavitation jet nozzle are essential indices to evaluate the jet performance. We established a simulation model of the jet process of the nozzle to investigate the evolution mechanism of the inner and outer flow fields. We used the chamber fillet, chamber diameter, chamber length, and outlet-tube diameter as the design variables, and the peak value of the striking force and the amplitude of the pulsation of the striking force as the target variables. The collaborative optimization design method of the nozzle was determined by combining the orthogonal test method, the back propagation neural network, and the nondominated sorting genetic algorithm. As indicated by the results, when the inlet pressure was 3 MPa, the factors ranked as follows in terms of their effects on the jet performance of the nozzle: the chamber fillet, the outlet-tube diameter, chamber diameter, and the chamber length. To verify the feasibility of the collaborative optimization method, the nozzle was fabricated via 3D printing, and the simulation model was verified by testing. This study provides support to the development of design theory for self-oscillating pulsed cavitation jet nozzles.
Cosmological solutions with time-delay
Authors: Paliathanasis Andronikos
Published: October 2022

We introduce a time-delay function in bulk viscosity cosmology. Even for bulk viscosity functions where closed-form solutions are known, because of the time-delay term, the exact solutions are lost. Therefore in order to study the cosmological evolution of the resulting models we perform a detailed analysis of the stability of the critical points, which describe de Sitter solutions, by using Lindstedt’s method. We find that for the stability of the critical points it depends also on the time-delay parameter, where a critical time-delay value is found which plays the role of a bifurcation point. For time-delay values near the critical value, the cosmological evolution has a periodic evolution, this oscillating behavior is because of the time-delay function. We find a new behavior near the exponential expansion point, which can be seen also as an alternative way to exit the exponential inflation.
Mediterranean onshore–offshore gradient in the composition and temporal turnover of benthic molluscs across the middle Piacenzian Warm Period
Authors: Dominici Stefano , Danise Silvia
Published: October 2022

The mid-Piacenzian Warm Period (mPWP: 3.3–3.0 Ma) is the most recent geological analogue of ongoing climate change and has been the subject of considerable interest for numerical models of the climate system. To verify the effect of the mPWP on diversity and temporal turnover of marine benthic communities, we evaluated changes in species-level abundance and the composition of Mediterranean Pliocene molluscs prior, during and after the mPWP. The Pliocene onshore–offshore gradient in species composition did not change during the mPWP (and continued basically unchanged up to the present day in the Mediterranean Sea), with most dominant species occupying the same rank in a given environment. During the mPWP, species evenness generally increased towards offshore environments. Within the three time intervals, temporal similarity is greater in offshore environments, except during the mPWP when offshore communities also exhibited greater dissimilarity. The temporal turnover in composition decreased again with depth as global temperatures decreased after the mPWP. The structure of mPWP communities suggests that warming and sea-level rise contributed to the expansion of vegetated bottoms (onshore) and shelly and coralligenous bottoms (offshore). Although the effects of mPWP warming did not change the onshore–offshore gradient in the long term, its effect disproportionately affected deeper environments, in contrast to colder climate regimes.
Understanding the Role of Carbon Mixtures on the Polarization of Sulfur Electrodes in Lithium-Sulfur Batteries
Authors: Irshad Ahamed , Elizalde-Segovia Rodrigo , Jayathilake B. S. , Zayat Billal , Narayanan S. R.
Published: October 2022

The performance of the sulfur-carbon composite cathode in a lithium-sulfur battery is chiefly determined by the nature of the carbon materials, the total sulfur content, and the distribution of sulfur within the composite electrode. Despite years of research, the role of these major factors in achieving optimal cathode performance is not well-understood. The present study uncovers the factors arising from formulation and processing that contribute to the internal resistance and rate capability of Ketjenblack-carbon based sulfur cathodes. Despite its enormous surface area, Ketjenblack-carbon-based sulfur electrodes exhibit surprisingly poor discharge rate capability and a high polarization resistance, providing no more than 180 mAh g−1 at the C/20 rate and delivering a high specific capacity of 1200 mAh g−1 only at a very low discharge rate of C/50. Our studies uncovered that a large contribution to the polarization resistance that arises from inter-particulate contacts and charge-transfer processes occurred close to 30% depth of discharge whereupon sulfur formed thick insulating sheets on the Ketjenblack particles, requiring an additional electron-percolation pathway for reducing the polarization. By the addition of a low-surface area carbon, Super-P®, such an electron conduction pathway could be achieved; the internal resistance of the Ketjenblack cathode decreased by four times and the electrode delivered an impressive capacity of 950 mAh g−1 at C/5 rate. We anticipate that the detailed analysis of impedance and the new learnings from this study will provide the insight needed for improving the formulation and design of the sulfur cathode.
Displacement Pattern of Anterior and Posterior Column Fragments in Both‐Column Acetabular Fractures: A 3D Reconstruction‐Based Study
Authors: Ye Pengyu , Guo Junfei , Wang Zhongzheng , Tian Siyu , Zhao Kuo , Yin Yingchao , Hou Zhiyong , Zhang Yingze
Published: October 2022

Background. Few studies have been conducted to examine the displacement characteristics of both‐column acetabular fractures (BCAFs). The goal of this study was to investigate the displacement pattern of anterior column (AC) and posterior column (PC) fragments in BCAFs using 3D virtual software. Materials and Methods. BCAFs were retrospectively reviewed, and 81 patients were enrolled. Computed tomography (CT) images were imported into Mimics software. A 3D model of each pelvis was generated. Four marked points and the rotation angle of each of the injured ACs and PCs were identified. The fracture fragments were reduced virtually using the software, and the change in coordinates of the marked points after reduction was recorded while the rotation angle was measured. The measurements of positional and directional displacement were analysed using the Mann–Whitney U test and the binomial test, respectively. Results. There was a propensity for AC fragments to shift superomedially and to rotate externally (p < 0.001). Additionally, the posteroinferior fracture area of AC fragments showed the greatest displacement (p < 0.05). PC fragments moved superomedially (p < 0.001) and moved more at the proximal end than the distal end (p < 0.001). PC displacement was always accompanied by internal rotation (p < 0.001). Greater AC displacement was observed in the fracture area further away from the acetabulum (p < 0.05). Greater rotation was observed for the AC than the PC (p < 0.001). Conclusion. After a BCAF occurs, there are regular patterns regarding the direction and distance of AC and PC fragment displacement. Information on these patterns may provide insight into the injury mechanism and fracture morphology and facilitate surgical decision‐making for orthopaedic trauma surgeons.
Research on Optimization of Injection Molding Process Parameters of Automobile Plastic Front-End Frame
Authors: Yang Kai , Tang Lingfeng , Wu Peng
Published: October 2022

The main objective of the present article is to obtain the optimum technological parameters of the automobile plastic front-end frame. Moldflow software was used to simulate the injection molding of the automobile plastic front-end frame bracket in this study. The uniformity experiment was designed and completed. Five injection molding process parameters, including mold temperature, melt temperature, packing pressure, injection time, and packing time, were selected as experimental factors. Volume shrinkage and warpage amount were selected as quality evaluation indexes. Statistical Product Service Solutions (SPSS) software was used to perform linear regression analysis on the test results, respectively, and the linear regression equation corresponding to the two evaluation indexes was obtained. Then, regression equation analysis was carried out to obtain the optimal process parameter combination of the volume shrinkage and the warpage amount. A back propagation (BP) neural network model with input as a process parameter and output as an evaluation index is established by MATLAB and optimized by a genetic algorithm (GA). Finally, the optimized neural network model was used to predict the combination of process parameters with the minimum volume shrinkage and warpage amount. Based on the performed simulations, the minimum volume shrinkage and the minimum amount of warping in the optimal design were 13% and 0.7062 mm, respectively. The corresponding combination of process parameters was the mold temperature of 75.5°C, the melt temperature of 285.32°C, the packing pressure of 42.32 MPa, the injection time of 3.45 s, and the packing time of 60 s. According to the optimal process parameters, the volume shrinkage and warpage amount of the automobile plastic front-end frame have reached the optimal state at the same time, which improves the quality of injection molding and reduces production and processing costs. It has a certain guiding significance.
Pricing and Assortment Decision of Competitive Omnichannel Selling Strategy: Considering Online Return Cost
Authors: Huang Xin , Guo Shujun
Published: October 2022

In the age of new retailing, consumers are discovering brands in new ways and seeking new conveniences to guide their purchasing decisions. Increasingly, retailers are offering consumers a cohesive and comprehensive experience across digital and physical touchpoints by integrating online and offline channels. This study considers a competitive market structure with two retailers selling four products via both online and offline channels. The retailers act as the decision maker of both the product assortment strategy and pricing strategy. Consumers are heterogenous in their horizontal fitness regarding each product, while they are common in the return probability when facing a deceptive product. Consumers’ purchase decision of whether to purchase through physical stores or online stores and making a purchase from which retailers depend on not only the product assortment strategies across competitive retailers but also the return cost that the consumers are faced with if product return happens. Results show that the online product return cost plays an important role in the retailers’ optimal pricing strategy design and product assortment strategy design. To be specific, the optimal prices of products that are sold through the online channel first increase in the return cost of the online product and then decrease it; while the optimal prices of products sold offline are always increasing in the online product return cost. Moreover, no matter what placement strategy sellers will choose, the optimal profit of both sellers is first decreasing the return cost of the online product and then increasing it. Our analyses also depict a two-dimensional market structure by considering sellers’ return costs and consumers’ misfit costs to investigate the optimal selling strategies under the cross-channel shopping platform.
Extracellular Vesicle-Mediated Transfer of LncRNA IGFL2-AS1 Confers Sunitinib Resistance in Renal Cell Carcinoma
Authors: Pan Yihui , Lu Xuanxuan , Shu Guannan , Cen Junjie , Lu Jun , Zhou Mi , Huang Kangbo , Dong Jiaqi , Li Jiaying , Lin Haishan , Song Hongde , Xu Quanhui , Han Hui , Chen Zhenhua , Chen Wei , Luo Junhang , Wei Jinhuan , Zhang Jiaxing
Published: October 2022

Sunitinib resistance remains a serious challenge to the treatment of advanced and metastatic renal cell carcinoma (RCC), yet the mechanisms underlying this resistance are not fully understood. Here, we report that the long noncoding RNA IGFL2-AS1 is a driver of therapy resistance in RCC. IGFL2-AS1 was highly upregulated in sunitinib-resistant RCC cells and was associated with poor prognosis in patients with clear cell RCC (ccRCC) who received sunitinib therapy. IGFL2-AS1 enhanced TP53INP2 expression by competitively binding to hnRNPC, a multifunctional RNA-binding protein that posttranscriptionally suppresses TP53INP2 expression through alternative splicing. Upregulated TP53INP2 enhanced autophagy and ultimately led to sunitinib resistance. Meanwhile, IGFL2-AS1 was packaged into extracellular vesicles through hnRNPC, thus transmitting sunitinib resistance to other cells. N6-methyladenosine modification of IGFL2-AS1 was critical for its interaction with hnRNPC. In a patient-derived xenograft model of sunitinib-resistant ccRCC, injection of chitosan-solid lipid nanoparticles containing antisense oligonucleotide-IGFL2-AS1 successfully reversed sunitinib resistance. These findings indicate a novel molecular mechanism of sunitinib resistance in RCC and suggest that IGFL2-AS1 may serve as a prognostic indicator and potential therapeutic target to overcome resistance.

Significance:

Extracellular vesicle-packaged IGFL2-AS1 promotes sunitinib resistance by regulating TP53INP2-triggered autophagy, implicating this lncRNA as a potential therapeutic target in renal cell carcinoma.
The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: October 2022

Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long noncoding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid–liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line–based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for patients with esophageal cancer. Overall, this study uncovers the physiologic roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR–ILF3–HIF1α axis as a potential target for cancer therapy.

Significance:

Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid–liquid phase separation and activation of HIF1α signaling to promote cancer progression.
Polymethylmethacrylate Membrane Dialyzer: Historic but Modern
Authors: Torii Yuichi , Yamada Satoko , Yajima Mayumi , Sugata Toru
Published: October 2022

Polymethylmethacrylate (PMMA) hollow fiber membranes are one of the synthetic polymer hollow fiber membranes used to the hollow fiber artificial kidney. A PMMA hollow fiber membrane (PMMA membrane) has unique properties including the uniform structure and the adsorption property. Hemodialyzers using PMMA membranes, Filtryzer®, were approved in Japan in 1977 and have been used worldwide for over 40 years and so is a historical hemodialyzer.Various types in Filtryzer® having different pore sizes are developed and used in the clinical field. Filtryzer® B3 is a low-flux dialyzer. Filtryzer® BK has three types having different pore sizes, and above all, BK-F has the largest pores in the Filtryzer® series. Filtryzer® BG has a more uniform membrane structure by using weak anionic polymers compared with the earlier Filtryzer® series to remove β2-MG more. Filtryzer® NF is the latest Filtryzer® series and was developed as a dialyzer having improved antithrombogenicity compared with previous models and having protein adsorption property as the same with them. There have been many reports concerning Filtryzer® including improvement of patients’ symptoms such as pruritus and nutrition on the advantages for dialysis patients. Although PMMA membranes are historic dialysis tools used for over 40 years, they are also modern dialysis membranes that have been updated to respond to dialysis therapy at those time.
S-Nitrosylation-Mediated Reduction of Ca
V
1.2 Surface Expression and Open Probability Underlies Attenuated Vasoconstriction Induced by Nitric Oxide
Authors: Hu Zhenyu , Zhang Bo , Lim Leon Jian Ying , Loh Wei Zhern Kelvin , Yu Dejie , Tan Bryce Wei Quan , Liang Mui Cheng , Huang Zhongwei , Leo Chen Huei , Huang Hua , Soong Tuck Wah
Published: October 2022

Background:

L-type Ca
V
1.2 calcium channel, the primary gateway for Ca
2+
influx in smooth muscles, is widely regulated by multiple posttranslational modifications, such as protein kinase-mediated phosphorylation and nitric oxide-induced S-nitrosylation. However, the effect of S-nitrosylation on Ca
V
1.2 channel function and its role in arterial contractility are not well understood.

Methods:

Electrophysiological recordings, Ca
2+
and confocal imaging, and biochemical assays were used to functionally characterize S-nitrosylated Ca
V
1.2 channels in vitro, while pressure myography and tail-cuff blood pressure measurement were conducted to evaluate the physiological effects of Ca
V
1.2 S-nitrosylation ex vivo and in vivo.

Results:

S-nitrosylation significantly reduced the Ca
V
1.2 current density by promoting lysosomal degradation that leads to decreased levels of total and surface Ca
V
1.2 channel proteins in a Ca
V
β-independent manner and reducing the open probability of Ca
V
1.2 channel. Mechanistically, the Cys1180 and Cys1280 residues within Ca
V
1.2 channel have been determined as the molecular targets for S-nitrosylation as substitution of either Cys1180 or Cys1280 for serine resulted in substantial reduction of S-nitrosylation levels. Of note, Ca
V
1.2 S-nitrosylation levels were significantly reduced in arteries isolated from both spontaneously hypertensive rats and patients with pulmonary hypertension. Moreover, mouse resistance arteries incubated with S-nitrosocysteine displayed much lower contractility and spontaneously hypertensive rats injected with S-nitrosocysteine also showed significantly reduced blood pressure, suggesting that reduced S-nitrosylation contributes to the upregulation of Ca
V
1.2 channel activity in hypertensive arteries.

Conclusions:

This study provides strong evidence that S-nitrosylation-mediated downregulation of Ca
V
1.2 channels is via 2 distinctive mechanisms and the findings offer potential pathways for therapeutic inventions in hypertension.
Towards a Judicial r2p: The International Court of Justice and the Obligation to Prevent Genocide in The Gambia v. Myanmar Case
Authors: Pezzano Luciano
Published: October 2022

This article proposes a reading of the 2020 Order on Provisional Measures in The Gambia v. Myanmar case through the r2p lens. It holds that the International Court of Justice (icj), notwithstanding its inherent limitations as a judicial organ, can play an important role in the responsibility of the international community to help to protect populations from genocide, and that a ‘judicial r2p’ can exist under r2p’s Pillar Three. To that end, the article develops two main arguments. First, that in the 2020 Order, the icj used a language closer to r2p than ever. Second, that, by submitting the dispute to the Court, The Gambia not only has exercised a right under the Genocide Convention, but it also fulfilled its obligation to prevent genocide, and as a member of the international community, has contributed to activate the latter’s r2p regarding the Rohingya in Myanmar.
The genus Psilotreta Banks (Trichoptera, Odontoceridae) in Japan
Authors: KAWASE NAOKI
Published: October 2022

The Japanese species of Psilotreta Banks (Trichoptera, Odontoceridae) are reviewed. Five described species and three new species are recognized: P. japonica (Banks 1906), P. kisoensis Iwata 1928, P. voluta Kawase 2021, P. moritai Kawase 2021, P. flavida Kawase 2021, P. spatulata sp. nov., P. atrocaudata sp. nov., and P. bitubercula sp. nov. Adults of the three new species are described and those of P. japonica and P. kisoensis are redescribed. Illustrations of male and female genitalia of the remaining three species are provided for comparison. The larva of P. spatulata sp. nov. is described and those of P. japonica and P. kisoensis are redescribed. The larva of P. voluta is indistinguishable from that of P. spatulata sp. nov.
Rhithrops capensis gen. et sp. nov., a new aquatic dryopid beetle from the Western Cape of South Africa (Coleoptera: Dryopoidea: Dryopidae)
Authors: BILTON DAVID T. , SHEPARD WILLIAM D.
Published: October 2022

Rhithrops capensis gen. et sp. nov. is described from the Matjies River, in the Cedeberg range of the Western Cape Province, South Africa. The new genus is apparently related to the South African endemic genera Rapnus Grouvelle, 1899 and Strina Redtenbacher, 1867, but exhibits a number of distinct character states, including gibbosities outside the sublateral pronotal furrows and a transversely upturned labral apex, unique within the family. Rhithrops gen. nov. was collected from around the roots of aquatic plants in fast flowing deep water runs, as well as being sampled in nocturnal drift nets. The new species has relatively long legs and well-developed tarsal claws, and appears to be adapted to an entirely aquatic, benthic existence. A revised key is provided to the dryopid genera of South Africa.
Sixth contribution to the study of the Lithosiini of Gabon: the genus Pseudopoliosia Krüger, 2015 (Lepidoptera: Erebidae: Arctiinae)
Authors: DURANTE ANTONIO , APINDA-LEGNOUO EMELIE ARLETTE
Published: October 2022

The genus Pseudopoliosia Krüger, 2015 is recorded for the first time in Gabon. Two new species are described, and a checklist and keys to the species are provided.
A new genus of fruit fly in subfamily Dacinae (Diptera: Tephritidae) from India
Authors: DAVID K.J. , HANCOCK D.L. , GRACY R.G. , SACHIN K.
Published: October 2022

A new genus and species of fruit fly, Dacimita curvifasciatus David & Hancock, gen. et sp. n. is described from Meghalaya, India. It morphologically resembles Ichneumonopsis Hardy and Monacrostichus Bezzi, the former of uncertain tribal placement and the latter included in tribe Dacini. Phylogenetic analysis based on morphological and molecular characters revealed Dacimita curvifasciatus to be best placed in tribe Gastrozonini in subfamily Dacinae.
Multiyear La Niña Events and Multiseason Drought in the Horn of Africa
Authors: Anderson Weston , Cook Benjamin I. , Slinski Kim , Schwarzwald Kevin , McNally Amy , Funk Chris
Published: October 2022

One of the primary sources of predictability for seasonal hydroclimate forecasts are sea surface temperatures (SSTs) in the tropical Pacific, including El Niño–Southern Oscillation. Multiyear La Niña events in particular may be both predictable at long lead times and favor drought in the bimodal rainfall regions of East Africa. However, SST patterns in the tropical Pacific and adjacent ocean basins often differ substantially between first- and second-year La Niñas, which can change how these events affect regional climate. Here, we demonstrate that multiyear La Niña events favor drought in the Horn of Africa in three consecutive seasons [October–December (OND), March–May (MAM), OND]. But they do not tend to increase the probability of a fourth season of drought owing to the sea surface temperatures and associated atmospheric teleconnections in the MAM long rains season following second-year La Niña events. First-year La Niñas tend to have both greater subsidence over the Horn of Africa, associated with warmer waters in the west Pacific that enhance the Walker circulation, and greater cross-continental moisture transport, associated with a warm tropical Atlantic, as compared to second-year La Niñas. Both the increased subsidence and enhanced cross-continental moisture transport favors drought in the Horn of Africa. Our results provide a physical understanding of the sources and limitations of predictability for using multiyear La Niña forecasts to predict drought in the Horn of Africa.
From Strange to Normal: Computational Approaches to Examining Immigrant Incorporation Through Shifts in the Mainstream
Authors: Voyer Andrea , Kline Zachary D. , Danton Madison , Volkova Tatiana
Published: October 2022

This article presents a computational approach to examining immigrant incorporation through shifts in the social “mainstream.” Analyzing a historical corpus of American etiquette books, texts from 1922–2017 describing social norms, we identify mainstream shifts related to long-standing groups which once were and may currently still be seen as immigrant outsiders in the United States: Catholic, Chinese, Irish, Italian, Jewish, Mexican, and Muslim groups. The analysis takes a computational grounded theory approach, combining qualitative readings and computational text analyses. Using word embeddings, we operationalize the chosen groups as focal group concepts. We extract sections of text that are salient to the focal group concepts to create group-specific text corpora. Two computational approaches make it possible to examine mainstream shifts in these corpora. First, we use sentiment analysis to observe the positive sentiment in each corpus and its change over time. Second, we observe changes in each corpus's position on a semantic dimension represented by the poles of “strange” and “normal.” The results indicate mainstream shifts through increases in positive sentiment and movement from strange to normal over time for most of the group-specific corpora. These research techniques can be adapted to other studies of social sentiment and symbolic inclusion.
25-year Follow-up of Primary Tibial Periosteal Graft for Hard Palate Repair in Cleft Lip and Palate: Outcomes, Concerns and Controversies
Authors: Rizzo Maria Ida , Cajozzo Marta , Bucci Daria , Pistoia Angelica , Palmieri Annapina , Rajabtork Zadeh Oriana , Palmieri Giancarlo , Spuntarelli Giorgio , Zama Mario
Published: October 2022

Objective

This study evaluates long-term outcomes in adults with Unilateral and Bilateral Cleft Lip and Palate (UCLP/BCLP) treated during the period 1992 to 1995 with tibial periosteal graft in primary repair.

Design

Retrospective study.

Setting

Department of Plastic and Maxillofacial Surgery, Children's Hospital Bambino Gesù (Italy).

Patients

The study included 52 patients with non-syndromic BCLP/UCLP who met the inclusion criteria.

Interventions

All patients underwent a standardized surgical protocol using a tibial periosteal graft as primary repair of the hard palate.

Main Outcome Measure(s)

Long-term outcomes on maxillary growth, residual oronasal fistula, and leg length discrepancy.

Results

About <2% of patients showed oral–nasal communication. Mean value of maxillary depth was 86° ± 4.5°. The lower value for maxillary retrusion was 76.8° in relation to the Frankfurt plane. At the x-ray control, 12.2% of patients showed leg discrepancy with a difference of always <2 cm.

Conclusions

The rate of maxillary retrusion obtained was the same if compared to other techniques. Tibial periosteal graft reduces the risk of fistula and the need for reintervention after secondary bone graft. The study did not observe negative impacts on leg growth after 25 years.
Data-driven scalable pipeline using national agent-based models for real-time pandemic response and decision support
Authors: Bhattacharya Parantapa , Chen Jiangzhuo , Hoops Stefan , Machi Dustin , Lewis Bryan , Venkatramanan Srinivasan , Wilson Mandy L. , Klahn Brian , Adiga Aniruddha , Hurt Benjamin , Outten Joseph , Adiga Abhijin , Warren Andrew , Baek Young Yun , Porebski Przemyslaw , Marathe Achla , Xie Dawen , Swarup Samarth , Vullikanti Anil , Mortveit Henning , Eubank Stephen , Barrett Christopher L. , Marathe Madhav
Published: October 2022

This paper describes an integrated, data-driven operational pipeline based on national agent-based models to support federal and state-level pandemic planning and response. The pipeline consists of ( i) an automatic semantic-aware scheduling method that coordinates jobs across two separate high performance computing systems; ( ii) a data pipeline to collect, integrate and organize national and county-level disaggregated data for initialization and post-simulation analysis; ( iii) a digital twin of national social contact networks made up of 288 Million individuals and 12.6 Billion time-varying interactions covering the US states and DC; ( iv) an extension of a parallel agent-based simulation model to study epidemic dynamics and associated interventions. This pipeline can run 400 replicates of national runs in less than 33 h, and reduces the need for human intervention, resulting in faster turnaround times and higher reliability and accuracy of the results. Scientifically, the work has led to significant advances in real-time epidemic sciences.
Prenatal Diagnosis and Outcome of Intrapericardial Teratoma: Report of Two Clinical Scenarios
Authors: Martínez-García Alfonso , Cervantes-Salazar Jorge , Copado-Mendoza Diana Yazmín , Aranda-Fraustro Alberto , Barrera-Valdivieso María Alexandra , Pereira-López Gabriela Isabel , Calderón-Colmenero Juan
Published: October 2022

Intrapericardial teratoma is a rare tumor composed of tissue from the three germ cell layers with a rapid growth that may cause severe hemodynamic complications due to compressive effects. We present two clinical cases: the first case had severe fetal heart failure with fatal outcome, and the second underwent surgical treatment during the immediate postnatal period with a favorable evolution. Although teratomas are histologically benign tumors, rapid growth can cause serious hemodynamic complications. The importance of prenatal diagnosis is to allow appropriate monitoring of tumor growth and establish a prompt therapeutic plan. Opportune surgical treatment can prevent death and improve the prognosis of these patients.
Characteristics of the raw materials of glazed tile bodies in the southern area of the Bao'ensi site, Nanjing, China
Authors: Zhao Weijuan , Zhao Dan , Wu Bo , Li Bo , Zhou Baohua , Cui Jianfeng , Chen Qinlong
Published: October 2022

The Nanjing Bao'ensi site is the largest and highest-ranking royal temple from the Ming Dynasty, and it is famous for its full-body glass pagoda. In this study, the glazed tiles excavated from the southern area of the Bao'ensi site were selected and analysed using X-ray diffraction, thermal dilation and energy-dispersive X-ray fluorescence to determine their phase composition, firing temperature and chemical composition. The glazed tile bodies of the Bao'ensi site consist mainly of quartz and mullite, although some samples contain trace amounts of other minerals. All of the body samples were fired to the same temperature range (i.e. 1000–1100°C). The firing temperature combined with the phase composition indicate that the raw materials and firing process of the glazed tile body samples have similarities, but there are certain differences. The source of the raw materials for a portion of the glazed tile bodies is Dangtu, Anhui, whilst the source of the raw materials for the remaining materials remains to be discovered.
Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial
Authors: Daver Naval G. , Dail Monique , Garcia Jacqueline S. , Jonas Brian A. , Yee Karen W. L. , Kelly Kevin R. , Vey Norbert , Assouline Sarit , Roboz Gail J. , Paolini Stefania , Pollyea Daniel A. , Tafuri Agostino , Brandwein Joseph M. , Pigneux Arnaud , Powell Bayard L. , Fenaux Pierre , Olin Rebecca L. , Visani Giuseppe , Martinelli Giovanni , Onishi Maika , Wang Jue , Huang Weize , Green Cherie , Ott Marion G. , Hong Wan-Jen , Konopleva Marina Y. , Andreeff Michael
Published: October 2022

This phase 1b trial (NCT02670044) evaluated venetoclax-idasanutlin in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) ineligible for cytotoxic chemotherapy. Two-dimensional dose escalation (DE, n = 50) was performed for venetoclax daily with idasanutlin on days 1 to 5 in 28-day cycles, followed by dosing schedule optimization (n = 6) to evaluate reduced venetoclax schedules (21-/14-day dosing). Common adverse events (occurring in ≥40% of patients) included diarrhea (87.3% of patients), nausea (74.5%), vomiting (52.7%), hypokalemia (50.9%), and febrile neutropenia (45.5%). During DE, across all doses, composite complete remission (CRc; CR + CR with incomplete blood count recovery + CR with incomplete platelet count recovery) rate was 26.0% and morphologic leukemia-free state (MLFS) rate was 12%. For anticipated recommended phase 2 doses (venetoclax 600 mg + idasanutlin 150 mg; venetoclax 600 mg + idasanutlin 200 mg), the combined CRc rate was 34.3% and the MLFS rate was 14.3%. Pretreatment IDH1/2 and RUNX1 mutations were associated with higher CRc rates (50.0% and 45.0%, respectively). CRc rate in patients with TP53 mutations was 20.0%, with responses noted among those with co-occurring IDH and RUNX1 mutations. In 12 out of 36 evaluable patients, 25 emergent TP53 mutations were observed; 22 were present at baseline with low TP53 variant allele frequency (median 0.0095% [range, 0.0006-0.4]). Venetoclax-idasanutlin showed manageable safety and encouraging efficacy in unfit patients with R/R AML. IDH1/2 and RUNX1 mutations were associated with venetoclax-idasanutlin sensitivity, even in some patients with co-occurring TP53 mutations; most emergent TP53 clones were preexisting. Our findings will aid ongoing/future trials of BCL-2/MDM2 inhibitor combinations. This trial was registered at www.clinicaltrials.gov as #NCT02670044.
A novel pH- and glutathione-responsive drug delivery system based on in situ growth of MOF199 on mesoporous organic silica nanoparticles targeting the hepatocellular carcinoma niche
Authors: Ling Jiaji , Jiang Yongmei , Yan Shaoying , Dang Hao , Yue Huan , Liu Kanglin , Kuang Linghan , Liu Xingxin , Tang Hua
Published: October 2022

Background

For people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed.

Methods

In order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo.

Results

This newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94.

Conclusions

The in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy.
Low-dose interleukin-2 can improve salivary secretion but not lymphocyte infiltration of salivary glands in a murine model of Sjögren’s syndrome
Authors: Wen Junsong , Zhu Fenglin , Yu Xi , Xie Hualing , Li Chengyin
Published: October 2022

Introduction/aim

Effects of low-dose interleukin-2 (IL-2) on the exocrine glandular glands of Sjögren’s syndrome are unknown. The aim of this study was to investigate the effects of low-dose IL-2 on salivary gland structure and function in a murine model of Sjögren’s syndrome.

Materials and methods

Non-obese diabetic/Ltj (NOD) mice were used as the animal model of Sjögren’s syndrome, and low-dose IL-2 or phosphate buffered saline was administered subcutaneously from 5 weeks of age, while ICR mice were used as controls. Some mice were sacrificed at 9 weeks of age, while the other mice that continued to receive treatment were sacrificed at 23 weeks. We determined the salivary flow rate of mice every 3 weeks during the intervention. After the mice were sacrificed, one submandibular gland was removed for pathological evaluation, while the other submandibular gland was used to measure the levels of 25 cytokines by Luminex technology. Cervical lymph nodes and spleens were examined by flow cytometry for the proportions of CD8+T cells and Treg cells.

Results

The results showed that the salivary flow rate of NOD mice was slower than that of control-group mice, and there were more pathological changes in the submandibular gland. The levels of many cytokines in the submandibular gland were elevated. The proportion of CD8+T cells in the cervical lymph nodes and spleens was increased; however, the proportion of Treg cells was decreased. After treatment with IL-2, the exocrine function of the salivary glands of mice was improved. IL-2 also promoted the proliferation of Treg cells in the cervical lymph nodes and spleens, but it did not alter the extent of lymphocyte infiltration in the submandibular gland. The levels of cytokines in the submandibular glands, as well as the proportion of CD8+T cells in the cervical lymph nodes and spleens, were unchanged significantly after IL-2 treatment.

Conclusion

Our results demonstrate that treatment with low-dose IL-2 improves the secretory function of the exocrine glands of mice with Sjögren’s syndrome, but it does not reverse the structural damage of the exocrine glands.
Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes: an overview of systematic reviews
Authors: Crawford Fay , Nicolson Donald J. , Amanna Aparna E. , Smith Marie
Published: October 2022

Background

Reliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)].

Methods

Medline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews.

Findings

The overview identified 30 systematic reviews of patient education, footwear and off-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap.

Interpretation

The majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.
Unmet needs about iron deficiency in peritoneal dialysis: a Delphi consensus panel
Authors: Mazzaferro Sandro , D’Alonzo Silvia , Morosetti Massimo
Published: October 2022

Background

Anaemia and iron deficiency (ID) are common in chronic kidney disease (CKD) patients and related to outcomes. There is growing interest about the role of iron supplementation in CKD, particularly ferric carboxymaltose (FCM), also in relation to the use of erythropoiesis stimulating agents (ESAs). Despite a greater knowledge on ID management in patients receiving haemodialysis, a paucity of data exists about peritoneal dialysis (PD). Furthermore, the aim of this paper is to provide the results of a nationwide Italian survey about ID in PD using the Delphi method.

Methods

A list of 16 statements (48 items) was developed about four main topics: (1) approach to iron therapy in PD; (2) management experience about iron therapy in PD; (3) ESA and iron in PD; (4) pharmacoeconomic impact. Using the Delphi methodology, the survey was distributed online to 36 Italian nephrologists with expertise in PD, who rated their level of agreement with each item on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement.

Results

Twenty-five experts (70%) answered the survey. 35 items (73%) achieved a consensus (8 negative and 27 positive). In particular, the diagnosis of ID is widely known, but some doubts exist about how frequently test it. The use of I.V. iron seems to be routinary and can save money reducing the administration of ESAs. However, internal protocols are welcome.

Conclusions

Expert PD nephrologists know well the problem of ID and feel the necessity of shared protocols to optimize the iron therapy and consequently the use of ESAs.
Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer
Authors: Zhang He-Yang , Xie Hai-Lun , Ruan Guo-Tian , Zhang Qi , Ge Yi-Zhong , Liu Xiao-Yue , Tang Meng , Song Meng-Meng , Lin Shi-Qi , Yang Ming , Zhang Xiao-Wei , Xu Hong-Xia , Song Chun-Hua , Shi Han-Ping
Published: October 2022

Background

Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer.

Methods

This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan–Meier and Cox proportional hazards regression models were used to analyze long-term survival.

Results

A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose–response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan–Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time.

Conclusion

The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.
Overwork among resident physicians: national questionnaire survey results
Authors: Ishikawa Masatoshi
Published: October 2022

Background

Residents experience the longest working hours among physicians. Thus, it would be beneficial to perform a nationwide survey in Japan on residents’ long work hours and the background factors promoting upper limits on working hours of Japanese residents. The aim of this study was to study or assess the state of physicians’ excessive work hours and its background factors using a questionnaire survey.

Methods

The survey was sent to 924 hospitals. The physicians’ general attributes, work hours and conditions, and employers’ foundational entities were explored. Multiple logistic regression analysis was performed to elucidate the background factors for long work hours.

Results

Of the 4306 resident physicians who responded, 67% had ≥ 60 in-hospital hours/week and 27% had ≥ 80 h/week; 51% were on-call ≥ four times/month. Many of them hoped for increased remuneration. Additionally, female (reference: male, OR: 0.65, 95% CI: 0.55–0.76), 35–40 years old (reference: 25–30 years old, OR: 1.83, 95% CI: 1.32–2.54), childlessness (reference: child, OR: 1.41, 95% CI: 1.12–1.75), surgical specialization (reference: internal medicine, OR: 2.51, 95% CI: 1.96–3.23), neurosurgical specialization (reference: internal medicine, OR: 4.38, 95% CI: 2.92–6.59) and hospitals with 200–400 physicians (reference: <100 physicians, OR: 1.82, 95% CI: 1.12–2.96) exhibited significant correlations with ≥ 80 in-hospital hours/week.

Conclusion

Understanding the factors that increase the likelihood of residents working very long hours could aid in making targeted changes to address the specific concerns. Moreover, reducing working hours to a reasonable limit can improve resident physicians’ health and the quality of care they provide in their community.