bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatially organized tumor-stroma boundary determines the efficacy of immunotherapy in colorectal cancer patients
Authors: Zhang Rongxin , Feng Yu , Ma Wenjuan , Zang Yupeng , Guo Yanying , Li Young , Zhang Yixuan , Dong Xuan , Liu Yi , Zhan Xiaojuan , Pan Zhi-Zhong , mei Luo , Wu Miaoqing , Chen Ao , Chen Gong , Liu Longqi , Zhou Jingying
Published: January 2024

Colorectal cancer (CRC) patients with mismatch repair (MMR)-deficient (dMMR) but not MMR-proficient (pMMR) tend to benefit from immune checkpoint blockade (ICB) therapy. To uncover the rules governing these varied therapeutic responses, we integrated spatial enhanced resolution omics-sequencing (Stereo-seq), single-cell RNA sequencing, and multiplexed imaging analysis to create high-definition spatial maps of tumors from treatment-naïve and ICB-treated CRC patients. Our results identified the spatial organization and immune status of the tumor-stroma boundary as a distinctive feature of dMMR and pMMR CRCs, which determines ICB response. The physical interactions and abundance of LAMP3+ DCs and CXCL13+ T cells shape the ICB-responsive tumor-stroma boundary, whereas CXCL14+ cancer-associated fibroblasts remodel extracellular matrix to form a structural barrier in non-responders. Our work therefore uncovered the black box of how the molecular and cellular spatial structures of tumors determine ICB response, raising the possibility of reprogramming tumor-stroma boundary for sensitizing immunotherapies in the majority of CRCs.
Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores
Authors: Yang Weidong , yu wenlan , Tingey Mark , kelich joseph , Li Yichen , yu jinjie , Junod Samuel , jiang zecheng , Hansen Ian , Guessaymi Nacef
Published: January 2024

Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.
Fellow Eye Data for IOL Calculation in Eyes Undergoing Combined Phacovitrectomy
Authors: Kohnen Thomas , Kaiser Klemens , Bucur Julian , Jandeworth Tyll , Lwowski Christoph
Published: January 2024

Purpose To evaluate whether the intraocular lens (IOL) calculation of the fellow eye (FE) can be used in eyes undergoing combined phacovitrectomy.Methods In this retrospective, consecutive case series, we enrolled patients who underwent silicone oil (SO) removal combined with phacoemulsification and IOL implantation at the Department of Ophthalmology, Goethe University, Frankfurt, Germany. Preoperative examinations included biometry using the IOL Master 700 (Carl Zeiss Meditec AG, Jena, Germany). We used the IOL calculation of the FE (FE group) to calculate the prediction error compared with the IOL calculation using only the axial length of the FE (AL-FE group), as well as using the axial length (AL) of the operated eye (OE group) in addition to the measurable biometric parameters. For the IOL calculation, the Barrett Universal II formula was used. We compared the mean prediction error (MPE) as well as the mean (MAE) and median absolute prediction error (MedAE) with each other. In addition, the number of eyes with ± 0.50, ± 1.00, and ± 2.00 diopters (D) deviation from the target refraction was compared.Results In total, 79 eyes of 79 patients met our inclusion criteria. MedAE was lowest in the OE group (0.41 D), followed by FE group (1.00 D) and AL-FE group (1.02 D). Comparison between the AL-FE and FE groups showed no statistically significant difference (p = 0.712). Comparing eyes within ± 0.50 D of the target refraction, the OE group (50 eyes, 63.3%) performed best, followed by the AL-FE group (22 eyes, 27.8%) and the FE group (21 eyes, 26.6%).Conclusion Our results indicate no clinically relevant difference between using the IOL calculation of the fellow eye versus using only the axial length of the fellow eye in addition to the measurable parameters for the IOL calculation. A two-step procedure should always be strived for.
Mucilage effects on the soil water characteristics curve, mechanical consistency, and penetration resistance of compacted heavy and light texture soils.
Authors: Fathinejad Asma , Mohammadi Mohammad Hossein , Etesami Hassan , Zarebanadkouki Mohsen
Published: January 2024

Aims
This study aimed to investigate the effects of mucilage on soil mechanical properties and the soil water characteristic curve(SWC).
Methods
Six soil samples with a wide range of physical and chemical properties were taken and then SWC, soil penetration resistance(SR), and the Atterberg limits were measured at compaction pressures of 100, 200, 300, 400, and 600 kPa, and mucilage(extracted from chia seed)concentrations of 0, 0.1%, 0.3%, and 0.5%. Based on their texture and consistency, the studied soils were divided into two groups: sandy to loamy and clayey soils.
Results
Results showed that the effect of mucilage, especially at 0.1%, on the Atterberg limits was more significant for clayey soils. The mucilage reduces the compaction potential of light-texture soils and improves penetrability, especially when the soil is dry and under a high compaction pressure. This results in more water retention, especially at low matric suction. Mucilage causes fine-texture soils to be more prone to compaction. The inconsistent effects of mucilage on heavy and light-texture soils may be due to mucilage arrangement and concentration of the solution within fine and coarse pores.
Conclusion
It is concluded that the increase in water retention would be significant as long as the compressibility is not amplified due to the presence of the mucilage, especially under high compaction energy. The mucilage can improve water retention and penetrability, but tillage or any disturbance should be conducted with care for intensively cultivated soils, which may have higher root exudate concentration and compressibility than bare and fallow soils.
Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility
Authors: Stallmeyer Birgit , Bühlmann Clara , Stakaitis Rytis , Dicke Ann-Kristin , Ghieh Farah , Meier Luisa , Zoch Ansgar , MacLeod David MacKenzie , Steingröver Johanna , Okutman Özlem , Fietz Daniela , Pilatz Adrian , Escamilla Antoni Riera , Xavier Miguel , Ruckert Christian , Persio Sara Di , Neuhaus Nina , Gurbuz Ali Sami , Şalvarci Ahmend , May Nicolas Le , McEleny Kevin , Friedrich Corinna , Heijden Godfried van der , Wyrwoll Margot J. , Kliesch Sabine , Veltman Joris A. , Krausz Csilla , Viville Stéphane , Conrad Donald , O'Carroll Donal , Tüttelmann Frank
Published: January 2024

Piwi-interacting RNAs (piRNAs) are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4 as novel disease genes. The testicular phenotypes repeatedly differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal spermatozoa. LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. Furthermore, an abolished expression of not only the encoded proteins but also of additional piRNA factors reveals co-dependencies within the human pathway. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells.
Digital platforms adoption by SMEs in emerging markets. Are they beneficial amid high uncertainty?
Authors: Feitosa Paulo Henrique Assis , Chiarini Tulio , Neto Victo da Silva
Published: January 2024

The authors have requested that this preprint be removed from Research Square.
Predicting Carbon Dioxide Emissions in the United States of America Using Machine Learning Algorithms
Authors: Chukwunonso Bosah Philip , Al-wesabi Ibrahim , Shixiang Li , AlSharabi Khalil , Al-Shamma’a Abdullrahman A. A. , Farh Hassan M. Hussein , Saeed Fahman , Kandil Tarek , Al-Shaalan Abdullah M.
Published: January 2024

In the past few decades, several nations have experienced air pollution and environmental difficulties because of carbon dioxide (CO2) emissions. One of the most crucial methods for regulating and maximizing CO2 emission reductions is precise forecasting. Four machine learning algorithms with high forecasting precision and low data requirements were developed in this study to estimate CO2 emissions in the United States (US). Data from a dataset covering the years 1973/01 to 2022/07 that included information on different energy sources that had an impact on CO2 emissions were examined. Then, four algorithms performed the CO2 emissions forecast from the layer recurrent neural network with 10 nodes (L-RNN), a feed-forward neural network with 10 nodes (FFNN), a convolutional neural network with two layers with 10 and 5 filters (CNN1), and convolutional neural network with two layers and with 50 and 25 filters (CNN2) models. Each algorithm's forecast accuracy was assessed using eight indicators. The three preprocessing techniques used are (1) Without any processing techniques, (2) Processed using max-min normalization technique, and (3) Processed using max-min normalization technique and decomposed by variation mode decomposition (VMD) technique with 7 intrinsic mode functions and 1000 iterations. The latter with L-RNN algorithm gave a high accuracy between the forecasting and actual values. The results of CO2 emissions from 2011/05 to 2022/07 have been forecasted, and the L-RNN algorithm had the highest forecast accuracy. The research makes significant literary contributions. One of the first studies to focus on predicting CO2 emissions in the USA using a combination of three preprocessing approaches and four machine-learning algorithms, predicting the number of overall CO2 emissions while also accounting for a broader range of inputs.
Exerting pulling forces in fluids by directional disassembly of microcrystalline fibres
Authors: Kudernac Tibor , Pantaleone Luis , Calicchia Eleonora , Martinelli Jacopo , Stuart Marc , Browne Wesley , Portale Giuseppe , Tych Katarzyna (Kasia)
Published: January 2024

Bio-molecular polymerization motors are molecular systems that use supramolecular (de-)polymerization to mediate the conversion of chemical potential into useful mechanical work. Microcrystallization is ideally suited to reverse-engineer this strategy in artificial systems since self-organization of molecules in a crystal lattice resembles the process of polymer growth/disassembly but with increased predictability of molecular events in a highly ordered microscopic structure. With the intent to explore new chemo-mechanical transduction strategies, we developed a synthetic mechanically-active molecular system that can generate forces via controlled disassembly while being freely suspended in fluid. The amphiphilic monomer self-assembles into rigid, high-aspect ratio microcrystalline fibres with assembly regulated by a coumarin-based pH switching motif. In the structures formed, the crystal morphology determines the monomer reactivity at the interface, resulting in anisotropic etching of the fibres. This effect is used to exert directional pulling forces on microscopic beads adsorbed on the crystal surface through weak multivalent interactions. Mechanistic insights were provided by optical tweezers force spectroscopy, which quantified a stall force of 2.3 pN (+/- 0.1 pN) exerted by this ratcheting mechanism and the mechanical work produced by the disassembly of the fibres.
Municipal solid waste composting with amendments reduces heavy metals hazard, ecological risks and greenhouse gases emission
Authors: Devi Manisha , Chaudhry Smita , Yadav Rajender Kumar , Yadav Gajender
Published: January 2024

Open dumping and landfilling of municipal solid waste (MSW) in India cause environmental hazards and greenhouse gases (GHGs) emissions. Therefore, studies require to assess the potential of aerobic composting of MSW to minimize these risks. This study evaluates the potential of MSW composting with or without some amendments (i.e. G-gypsum, ES-elemental sulphur and RS-rice straw) in minimizing these risks. The composition, physicochemical characteristics including heavy metals (HMs), the potential pollution hazards and GHGs emissions were assessed for the MSW collected from domestic and industrial sites of Haryana, India. Industrial MSW had higher pH (7.31) and HMs concentrations (e.g. Cr, Cd, Cu, Ni, Pb and Zn), than domestic MSW. HMs were found within the critical limits for both sites except Cr and Cu in industrial MSW. Composting lowered the HMs and ecological risk and increased N, P, K and organic carbon. Co-composting with amendments like gypsum, elemental sulphur and rice straw improved C:N ratio, nutrients concentration and accelerated the degradation process. The pollution indices enrichment factor, contamination factor, geoaccumulation index, ecological risk and potential ecological risk index indicated lower ecological risk and HMs concentration in domestic site MSW. On-site GHGs emission significantly differed in space and seasons. Emission of CO2, CH4 and N2O from domestic landfill site were 20%, 27% and 64% higher than industrial and higher in monsoon season, followed by summer and winter, respectively. The highest GHGs emission was from center (heap top) (924.58 mg m-2 h-1), followed by middle (805.23 mg m-2 h-1) and peripheral (717 mg m-2 h-1) area of sites. Use of ES and RS amendments in co-composting reduced up to 41% GHGs emission than landfill emissions. MSW co-composting with elemental sulphur and rice straw can be a potentially safer alternative for the management of both domestic and industrial MSW than open landfill dumping.
Orally Available Small Molecule Regulates TXNIP Expression and Glucagon Action for the Treatment of Diabetes
Authors: Wang Xiaolei , Luo Zhikuan , Han Jun , Tian Qiong , Jing Ruijun , Dong Ao , Li Lingzhi , Jia Hongbin , Lv Tinghong , Dang Yunkun , Lai Fan , Chen Shili , Ma XuSheng , Zheng Haixue
Published: January 2024

In the progression of diabetes, sustained glucagon secretion facilitates glucose production. Despite its significance, no treatments currently target this vital parameter. We employed the promoter sequence of thioredoxin-interacting protein (TXNIP) as a screening target, evaluated our in-house chemical library, and subsequently undertook high-throughput screening and optimization via various medicinal chemistry techniques. Our efforts led to the identification of SKL-1223, an orally administered, non-toxic small molecule capable of effectively regulating blood glucose levels in both streptozotocin-induced and obesity-induced (db/db) diabetic mice. Furthermore, our study elucidated the hypoglycemic effect of glucagon and its role in reducing hepatic glucose output. On a mechanistic level, SKL-1223 interacts with the E-box region of the TXNIP promoter, consequently suppressing TXNIP transcription and associated signaling pathways. Thus, our study introduces a novel compound, offering a fresh therapeutic avenue for diabetes beyond existing regimens.
Salicylic and jasmonic acid attenuate the salt stress effects in lettuce
Authors: Neto Hozano de Souza Lemos , Neto Hozano de Souza Lemos , Garita Sebastián Andrés , Bernardo Valeria Fernanda , Ruscitti Marcela Fabiana , Arango Maria Cecilia , Wahnan Laura Karina , Guimarães Marcelo de Almeida
Published: January 2024

Salt stress reduces growth and change physiological and biochemical responses of plants. Salicylic acid (SA) and jasmonic acid (JA) are plant hormones involved in plant defense metabolism against abiotic stress. Therefore, the objective was to evaluate whether the foliar application of SA and JA, isolated or combined, attenuate the salt stress effects, as well as its possible effects on the physiological, biochemical and growth responses of lettuce plants. The plants were arranged in a completely randomized design, factorial scheme, with three salinity levels (1.65; 3.65 and 7.65 dS m− 1) and foliar application of SA (0 and 500 µM) and JA (0 and 100 µM). Photosynthesis, transpiration, stomatal conductance, internal carbon concentration, chlorophyll content, malondialdehyde (MDA) content, proline, relative membrane conductivity, soluble proteins, total and reducing sugars and phenols of lettuce leaves and roots were determined. Under the highest salinity level, shoot and root fresh weight reduced by 21.84% and 13.80%. Gas exchange also reduced by salinity, except for net photosynthesis. The combined application (SA + JA) increased the total soluble sugar content in leaves by 74.23%. Under moderate salinity, application of these growth regulators isolated induced the highest total sugar content in leaves. Proline content in leaves was higher under the highest salinity level and without application of growth regulators. However, with SA application, leaf proline content was reduced by 37.92%, while root proline increased with SA application under the highest salinity level. Exogenous application of salicylic acid and jasmonic acid improve salt stress tolerance in lettuce plants, although jasmonic acid is more effective than salicylic acid.
Diffuse Idiopathic Skeletal Hyperostosis: Prevalence and Risk Factors
Authors: Madariaga Maria Cecilia , Groff Hannah , O’Malley Nicholas A. , Thompson Jeffery , Apazidis Alexios
Published: January 2024

Background
Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a degenerative disease of the spine which has been estimated to affect anywhere from 8–37% of the population. In addition, previous literature has shown an association between DISH and serious disability including dysphagia. Previous research detailing prevalence and risk factors for DISH, however, have been limited by studying homogenous populations.
Methods
Patients who received CT scans of the spine during hospital admission were included. Demographic data including age, sex, race/ethnicity, smoking history, alcohol use, and comorbidities were collected via chart review. DISH was defined as the presence of flowing ossifications along ≧ 4 contiguous vertebral bodies on CT. The location, number of levels, and side of ossification were also collected. Results were analyzed using t-test and chi-square analyses. Significance was set to p < 0.05
Results
1097 patients with CT scans were identified, revealing a DISH prevalence of 20.3%. Patients with DISH were significantly older than those without DISH and had significantly higher CCI scores when compared to the non-DISH cohort. Significant differences were also observed between ethnic groups. Men were found to have a significantly higher prevalence of DISH when compared to women. Finally, those with DM, PVD, Dementia, COPD, and CHF were noted to have higher prevalence of DISH when compared to those without DISH.
Evaluation of front limb gait variation overground at a walk in sound and lame dogs using a combination of diagnostic techniques
Authors: Granström Miriam Kjörk , Roepstorff Lars , Pettersson Kjerstin , Ljungvall Ingrid , Dimopoulou Maria , Peck Charlie , Bergström Annika
Published: January 2024

BackgroundKinetic and kinematic gait analysis is increasingly practised as a part of lameness evaluation in dogs. The aim of this study was to examine the normal short- and long-term variation in front limb gait in sound control dogs (CD) at a walk using seven selected variables of objective kinetic and kinematic gait analyses. Also, to compare the findings in CD to a group of front limb lame dogs with elbow osteoarthritis (OAD). An additional aim was to test a kinetic based graphic method for lameness detection; symmetry squares (SS). Study design: Prospective longitudinal study of client owned CD and OAD. Clinical and orthopaedic evaluations were performed to ensure soundness and detect and grade lameness. Seven kinetic and kinematic variables and SS were tested for lameness evaluation. The CD were divided into two subgroups, CD1 and CD2, and examined twice: CD1 with two months interval and CD2 with 3-4 hours interval. The OAD group was evaluated once and compared to the CD groups’ first examination.ResultsThirteen CD and 19 OAD were included. For CD1 and CD2, there were no significant differences in any examined variable between examination occasions. Total peak force/impulse symmetry and fore-hind peak force/impulse symmetry differed significantly between OAD and CD. Symmetry squares had a 74% agreement to subjective orthopaedic evaluations.Conclusions:In CD, no difference in the examined variables was seen between examination occasions. Four out of seven objective variables differed significantly between CD and OAD. The graphic SS method might have diagnostic potential for lameness detection.
Outcome of Open Knee Joint Injury among Trauma Patients Visiting Tibebe-ghion Specialized Hospital, Bahir-dar, Northwest Ethiopia, 2021
Authors: Wuhib Getachew , Wuhib Mekuriaw , Assefa Melatwork , Mekonn Leul
Published: January 2024

Background
Open knee joint injury is a deep traumatic laceration violating the joint capsule. This study aimed to asses’ outcomes and associated factors of open knee joint injury among trauma patients visiting Tibebe-Ghion specialized Hospital, North West Ethiopia, 2021
Methods
Institution based retrospective cross sectional study was conducted by reviewing medical records of 43 patients treated for open knee joint injury from January 2019 to July 2021 giving 86% response rate. Data was entered and exported by using Epi Data manager version 4.4 and was analyzed by using SPSS version 25. Chi-squared test was conducted and p value less than 0.05 were considered significant 0.05
Results
Fourteen (32.5%) of this study subjects had developed either infection or limbing on follow-up due to open knee injury. Majority injuries (58.1%) are caused by car accident. Presence of associated injury, wound size, time of wound closure, debridement as one management option, sex and diagnosis method were showed significant association with complication outcome. From the diagnosed infection 90% was septic arthritis. During the study period eight patients (18.6%) developed limbing on follow up.
Conclusion
The rate of complication as one outcome among open kee injury patient in the study area was significantly higher. Presence of associated injury, wound size, time of wound closure, debridement as one management option, sex and diagnosis method were showed significant association with complication outcome. Targeted public mobilization should be done to improve awareness about orthopedic emergencies and complication risk reduction to have favorable outcomes.
Bone Engineering Fluffy poly Lactide-co-glycolide/hydroxyapatite Composite Scaffold with Bone Marrow Mesenchymal Stem Cells: A Promising Strategy for Bone Defects Repair
Authors: yuan tao , meng jia , yang shaoqiang , Lai Cheng-Teng , Hong Qian , Xin Yu , Hui Jiang , Qing-Gang Cao , Xu Jianda , bao nirong
Published: January 2024

Treatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, additive manufacturing with altered properties and characteristics of polymers was introduced as a promising approach for bone defects. The present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. The micro-CT and histomorphological analysis showed higher mineralized tissue production in rabbit model treated with fluffy PLGA/HA composite scaffold. The obtained results proved a promising strategy to construct fluffy PLGA/HA composite scaffolds used in bone defects.
Association of Smoking Cessation With Dynapenia Among Older Current or Former Smokers in Korea
Authors: Yoo Keunjoong , Park Yong Soon , Kim Hye Jin , Kim Jeong Hyeon
Published: January 2024

Muscle strength is important for the health of older individuals. However, the global burden of cigarette smoking remains significant. We investigated the association between smoking cessation and dynapenia in older Korean adults. Data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2016–2019) were utilized, including 1,177 participants aged 65–79 years, excluding those who had never smoked. Dynapenia was defined as grip strength < 28 kg for men and < 18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariate logistic regression analysis evaluated the association between smoking cessation and dynapenia. Compared with former smokers, the odds ratio (OR; 95% confidence interval [CI]) of dynapenia in current smokers was 1.648 (1.069–2.541). The OR (95% CI) stratified by the years since smoking cessation were 0.678 (0.378–1.217), 0.487 (0.276–0.860), 0.598 (0.323–1.108), and 0.483 (0.229–1.019) in those who did not smoke for < 10, 10–20, 20–30, and > 30 years, respectively. The OR for dynapenia significantly decreased with the number of years since smoking cessation (P for trend = 0.026). Former smokers had a lower risk of dynapenia than current smokers, and dynapenia risk decreased with increasing duration of smoking cessation.
Clinical application of flexible bronchoscopy in neonatal respiratory diseases
Authors: Zhuang Xuee , liu zhiyong , Zheng Jingyang , xu jinglin , Chen Dongmei
Published: January 2024

Background: Respiratory diseases are an important component of neonatal diseases, and flexible bronchoscopy is increasingly used in neonates. This study aimed to investigate the value of bronchoscopy in neonatal respiratory abnormalities and to evaluate the safety of bronchoscopy application.
Methods: Clinical data and outcomes of 56 children who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were analyzed.
Results: A total of 56 children had a minimum body weight of 1200 g at the time of bronchoscopy, and the minimum gestational age at birth was 26+1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were dyspnea in 24 cases (42.9%), laryngeal tinnitus in 22 cases (39.3%), pulmonary atelectasis in 10 cases (17.6%), feeding difficulty in 10 cases (17.6%), and difficulty in extubation in 6 cases (10.7%). A total of 16 types of structural and functional abnormalities were detected in the respiratory tract. The most common symptoms were laryngomalacia in 29 cases (59.2%), tracheobronchial tenderness in 8 cases (16.3%), and vocal cord paralysis in 6 cases (12.2%). Bronchoalveolar lavage was performed in 39 cases. Eight children were diagnosed by bronchoscopy and then underwent thoracic or pentacameral surgery; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, and none died.
Conclusions: Flexible bronchoscopy plays an important role in diagnosing and identifying respiratory disorders in neonates and can be safely used in neonates with few serious complications.
Atypical clinical debut associated with Jarisch Herxheimer reaction in an asplenic patient with leptospirosis: case report and review
Authors: Maria Zarama-Eraso , Jhon Tipasoca-Pineda , Paola Sánchez-Herrera , Michel Pérez-Garzón
Published: January 2024

Background: Leptospirosis poses a diagnostic challenge owing to its wide array of symptoms, ranging from asymptomatic cases and febrile syndromes to severe disease with a high mortality rate. Risk factors are associated with exposure and the immune response, particularly in immunosuppressed patients.
Case presentation: A clinical case involving a 49-year-old patient with a history of splenectomy and no immunization schedule. The patient presented to the emergency room with non-specific symptoms, primarily myalgias, arthralgias, and emesis, initially suggestive of a viral infection. However, there was a rapid progression to hypoxemic respiratory failure, requiring invasive ventilatory support. Given the immune status due to spleen absence, antibiotic treatment with meropenem and linezolid was promptly initiated, to mitigate the risk of post-splenectomy sepsis. During antibiotic administration, the patient experienced febrile episodes, accompanied by chills, myalgias, and emesis, which gradually decreased in both duration and intensity. Ultimately, the patient exhibited satisfactory progress, successfully underwent extubation, and completed a 7-day antibiotic course. Final reports confirmed positive IgM for Leptospira.
Conclusion: Leptospirosis is a global zoonotic disease, displaying a diverse array of manifestations; recognized as a potential cause of undifferentiated fever, often confused with other prevalent tropical infections. The imperative to consider this diagnosis extends beyond the general population to encompass individuals in states of altered immunity. Recognizing and addressing leptospirosis in at-risk populations is crucial, as it can significantly impact the prompt initiation of treatment and, consequently, influence associated mortality rates.
Asymptomatic malaria parasitaemia and virological non-suppression among children living with HIV in Accra, Ghana: a cross-sectional study.
Authors: Afrane Adwoa K. A. , Alhassan Yakubu , Amoah Linda Eva , Nyarko Mame Yaa , Addo-Lartey Adolphina , Paintsil Elijah , Torpey Kwasi
Published: January 2024

Background
Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa, with co-infections having an impact on the outcomes of both. We assessed the association between asymptomatic malaria parasitaemia and virological non-suppression among children living with HIV attending a clinic at the Korle Bu Teaching Hospital (KBTH) and the Princess Marie Louis Hospital (PML) in the city of Accra, Ghana.
Methods
This was a cross-sectional study of asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML conducted from September to November 2022. Patients who had been on ART for at least 6 months were eligible to participate. Structured questionnaires were used to collect socio-demographic, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria and GeneXpert to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, Chi-square tests and logistic regression were utilized.
Results
The participants' median age was 9 years with a range of 6 to 12 years. Males made up 57% of the population. We detected 3.6% (10 of 277) and 7.6% (21 of 277) cases of malaria using microscopy and PCR, respectively. Virological non-suppression (VL > 1000 copies/ml) was seen in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had non-detectable viral load levels. There were no factors associated with malaria PCR positivity carriage. Poor adherence to antiretroviral therapy was associated with a fivefold increase in the risk of viral load non-suppression (AOR = 4.89 [CI = 2.00-11.98], p = 0.001).
Conclusion
The study showed that the proportion of children living with HIV with asymptomatic malaria parasitaemia was low, with about one third of the study population having virological non suppression. The interaction between malaria parasitemia and viral replication may not be the main culprit for virological non suppression.
“Six Thinking Hats”: Improving Thinking in Traditional Problem-based Learning Pathophysiology Curriculum for Medical Students
Authors: Ma Licai , Wu Di , Li Hongli , Ni Bing , Ouyang Lin , Zhang Zhihui , Deng Fang
Published: January 2024

Problem-based learning (PBL) was developed for medical education and is currently widely used in pathophysiology courses, one of the core fundamental curricula. Yet, PBL might lead to duplicate and biased discussion, and even invalid arguments. Moreover, students’ passive thinking, lack of self-reflection, feedback and guidance of critical thinking might influence tutorial quality. We aimed to introduced Six Thinking Hats into medical education through a hybrid PBL Pathophysiology curriculum to improve the efficiency of the lectures. 32 medical students from the Chinese People's Liberation Army Medical University were randomly assigned into experimental groups and control groups in spring semester of 2022. The Six Thinking Hats offered six directions on top of PBL pathophysiology classes to guide students’ thinking process in before-class preparation, classroom discussion and after-class feedback and self-reflection. The curriculum was evaluated using interviews, anonymous student surveys and exams scores. After finals, the high frequency glossaries from the interviews in the experimental groups are efficient, critical, time saving, emotional, control and focus and they felt that their way of thinking had changed. Students in the control groups have lower total exam scores (mean 76.50 ± 6.06 versus 80.88 ± 4.86, p = 0.032) and lower advanced case analysis scores (19.0 ± 3.01 versus 23.81 ± 2.14, p＜0.0001). Integrating Six Thinking Hats into PBL in pathophysiology curriculum was feasible and effective for medical students. It could provide an objective, comprehensive, effective, and positive class environment for medical students and may extend to a broader audience in medical education.
Robust design method and intelligent system for trimming die of complex automotive panel
Authors: Xilei Zhang , Guochao Deng , Zhibing Zhang , Yuqi Liu , Jikun Ta , Wang Zhen
Published: January 2024

The design process of automotive trimming die is very complicated, time-consuming and error-prone because of the complex geometric shape of the part surfaces and the trimming lines. This paper presents a robust design method for trimming die based on template subtraction and bounding volume strategy (TSBV) to unify different design process of trimming structure. The novel horizontal and vertical offset algorithms are developed to construct the quality derived surfaces based on geometric offset mapping (DS-GOM) quickly and stably, which are applied to generate the bounding surfaces of the template solids. A robust and intelligent design system for trimming die of automotive panel is implemented on NX platform in this paper. And the intelligent system is adopted to design the trimming die for the actual and classical automotive panels to verify the effectiveness and stability of the developed system. Case studies and industrial applications have demonstrated that the system can improve the design efficiency by 74.2% compared with generic design system.
Green synthesis of carbon quantum dots from Phragmites communis and its protective effect on Artemia salina under copper stress
Authors: Gang Xue , Li Meng , Lei Tianya , Zhang Hongmei , Wei Zhenlin
Published: January 2024

Carbon quantum dots (CQD) and Nitrogen-doped CQDs (N-CQDs) were synthesized through a one-step hydrothermal process, utilizing reed leaves and urea as carbon and nitrogen sources, respectively. The maximum excitation wavelength of CQDs and N2-CQDs was 325 nm, and the corresponding emission wavelength was 407 nm and 406 nm, respectively. Synthetic CQDs have excellent fluorescence properties, while N-doping enhances the fluorescence intensity and stability of CQDs. Next, the adsorption effect of N2-CQDs on various metal ions was also studied using the fluorescence quenching method. The results showed that N2-CQDs have a significant capacity for adsorption of Cu2+ ions. The following quantitative analysis indicated that the Cu2+ concentration showed an excellent linear relationship between 0 ~ 500 µmol/L and the limit of detection (LOD) was 0.074 µmol/L. The N2-CQDs at 0-200 µg/mL have no deleterious effects on the viability of HeLa cells and the survival rate of Artemia nauplii. Finally, the agarose gel containing N2-CQDs was constructed, and its absorption behavior of Cu2+ in artificial seawater was evaluated. The results showed that this N2-CQDs-based gel was able to efficiently remove Cu2+ from seawater, leading to a higher survival rate of the nauplii under 10 and 50 mg/L Cu2+ stress. Our results collectively provide a cost-effective method for removing heavy metal ions from seawater and mitigating their harmful effects on sea animals.
Engineering Complex Vectorial Light Field in Leaky-Wave Metasurfaces: Harnessing Structural Parameter-Independent Detour and Geometric Phases
Authors: Cheng Qingqing , Xi Kelei , Zhou Shaodong , Sheng Xiaohang , Gao Jingxiang , Li Lin , Zhou Lei , Zhuang Songlin
Published: January 2024

To generate arbitrary vector light fields, metasurfaces should exhibit tailored distributions of scattering amplitudes/phases of light waves for two orthogonal polarizations. The traditional approach to design such metasurfaces, involving sorting out meta-atoms consisting of multiple resonators with different structures, is complicated and time-consuming as it relies on an extensive structureparameter library obtained with full-wave simulations. Here, we propose an analytical approach to design metasurfaces for generating arbitrary vector light fields, under excitations of obliquely incident light or guided waves. In contrast to the previous approach replying on resonant phases of meta-atoms, our basic meta-atom consists of two identical perfect polarization convertors exhibiting tailored orientational angles and lateral positions, which determine respectively the geometric and detour phases of scattered waves and, in turn, the scattering phases of two polarizations. Moreover, the scattering amplitudes of two polarizations can be analytically determined by the relative angle of two resonators considering the interferences between waves scattered by them. These analytical expressions enable us to fast design metasurfaces exhibiting arbitrary pre-designed distributions of polarization-dependent scattering amplitudes and phases, without performing time-consuming numerical optimizations. For proof of concept, we theoretically showcase four-image loading on a leaky-wave metasurface, resulting in distinct images for near-field intensity distribution and phaseencoded far-field holography for x− and y−polarizations. Our study establishes a fundamental design principle for complete complex vector field control, applicable across a variety of physical platforms and frequencies.
Efficacy and safety of Kuoxin Formula in the treatment of dilated cardiomyopathy-related heart failure (Qi-Yin deficiency combined with blood stasis syndrome): study protocol of a randomized, double-blind, placebo-controlled, multi-center clinical trial
Authors: Wu Qiong , An Shiying , Lee Rueyjyh , Gao Dongwen , Zhou Yinyifan , Peng Longping , Yao Lei , Fu Deyu , Zhou Chang , Zhou Li , Gao Junjie , Yuan Suyun , Cao Min , Ma Mengjiao , Liu Chenyang , Mao Meijiao , Hu Chunrui , Deng Bing , Zhou Duan , Xu Yingjia , Wang Youhua
Published: January 2024

Background Dilated cardiomyopathy (DCM) is a severe condition characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes. Globally, and particularly in China, a notable challenge arises from the insufficient availability of targeted therapies demonstrating significant efficacy for DCM. Additionally, the application of traditional anti-heart failure drugs in DCM is constrained, as many patients exhibit a propensity for hypotension or show limited improvement in their heart failure symptoms. Kuoxin Formula (KXF), an internally agreed-upon prescription at Longhua Hospital, is supported by clear biological evidence for improving cardiac function and myocardial remodeling. Previous clinical studies have also demonstrated its potential to improve patients' quality of life. This trial aims to further evaluate the safety and efficacy of KXF in treating DCM -related heart failure.
Method This prospective, randomized, double-blind, placebo-controlled, multicenter trial recruits 230 patients diagnosed with DCM (Qi-Yin deficiency combined with blood stasis syndrome) from five centers. Participants will be randomly assigned in a 1:1 ratio to either the KXF treatment group or a placebo group. The treatment will span 12 weeks, during which key indicators and adverse events will be monitored. The primary outcome is the proportion of patients whose NT-proBNP decreased by more than 30%. The secondary outcomes include the NYHA functional classification, TCM syndrome scores, echocardiographic parameters, TGF-β, PICP, CITP, galectin-3, ST2 levels, 6MWT, Lee's heart failure score, and MLHFQ score.
Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of dilated cardiomyopathy. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.
Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023.
Impact of Time-History Terms on Reservoir Dynamics and Prediction Accuracy in Echo State Networks
Authors: Ebato Yudai , Nobukawa Sou , Sakemi Yusuke , Nishimura Haruhiko , Kanamaru Takashi , Sviridova Nina , Aihara Kazuyuki
Published: January 2024

The echo state network (ESN) is an excellent machine learning model for processing time series data. This model, utilizing the response of a recurrent neural network called a reservoir to input signals, achieves high training efficiency. Introducing time-history terms into the neuron model of the reservoir is known to improve the time series prediction performance of ESN, yet the reasons for this improvement have not been quantitatively explained in terms of reservoir dynamics characteristics. Therefore, we hypothesized that the performance enhancement brought about by time-history terms could be explained by delay capacity, a recently proposed metric for assessing the memory performance of reservoirs. To test this hypothesis, we conducted comparative experiments using ESN models with time-history terms, namely Leaky-Integrator ESNs (LI-ESN) and chaotic echo state networks (ChESN). The results suggest that, compared to ESNs without time-history terms, the reservoir dynamics of LI-ESN and ChESN can maintain diversity and stability while possessing higher delay capacity, leading to their superior performance. Explaining ESN performance through dynamical metrics are crucial for evaluating the numerous ESN architectures recently proposed from a general perspective and for the development of more sophisticated architectures, and this study contributes to such efforts.
Galectin-3 Impairs Calcium Transients and β-Cell Function
Authors: LI PINGPING , Jiang Qian , Zhao Qijin , Chen Yibing , Ma Chunxiao , Peng Xiaohong , Wu Xi , Liu Xingfeng , Wang Ruoran , Hou Shaocong , Kong Lijuan , Wan Yanjun , Wang Shusen , Meng Zhuo-Xian , Cui Bing , Chen Liangyi
Published: January 2024

In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) inβ-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS.β-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD- fed and db/db mice. Our results highlight a novel role of Gal3 in pancreatic β-cell dysfunction, and Gal3 could be a new therapeutic target for the treatment of type 2 diabetes.
Impulsivity mediates the association between narcissism and substance-related problems beyond the degree of substance use: a longitudinal observational study
Authors: Hildebrandt Malin K. , Noack Josepha , Wuellhorst Raoul , Endrass Tanja , Jauk Emanuel
Published: January 2024

Background
Narcissism has been implied as a putative risk factor for substance use disorders (SUDs). However, previous research did not disentangle the degree of substance use from substance-related problems, the symptoms of SUDs. This preregistered study addressed the open question whether grandiose and vulnerable narcissism and their constituent traits convey specific SUD risk, that is, explain substance-related problems beyond the degree of use. Furthermore, we tested whether impulsivity or substance use motives linked to narcissistic self-regulation mediate this association.
Methods
Narcissism, impulsivity, substance use motives, past-year substance use, and substance-related problems were assessed in 139 (poly-)substance users, 121 of whom completed a one-year follow-up. For significant longitudinal associations between narcissism factors and substance-related problems controlled for the degree of use, we tested impulsivity and substance use motives as mediators.
Results
Grandiose narcissism (r = .24, p = .007) and its constituent factors antagonistic (r = .27, p = .003) and agentic narcissism (r = .18, p = .050), but not vulnerable narcissism, prospectively predicted substance-related problems beyond the degree of substance use. Associations of grandiose narcissism and antagonistic narcissism with substance-related problems were fully mediated by impulsivity, but not substance use motives.
Discussion
We demonstrate that grandiose narcissism – particularly antagonistic but also agentic narcissism – is specifically linked to substance-related problems beyond the degree of substance use. The mediating effect of impulsivity but not substance use motives suggests that impulsivity may be a more important mechanism than narcissistic self-regulation in promoting SUD in narcissism. However, future studies may use more targeted measures than substance use motives to further probe the role of self-regulation. Similar result patterns for alcohol compared to all substances together indicate that mechanisms may be alike across substances. In conclusion, narcissistic individuals may not use substances more but have a higher SUD risk, informing prevention and treatment.