bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Analysis of TCP Fractional Window Increment and Adaptive Fractional Window on IEEE 802.11 Multihop Ad Hoc Networks
Authors: Sofyan Arnas , Suryani Vera , Nuha Hilal Hudan
Published: September 2023

TCP, a layer 4 transport protocol, plays a crucial role in both wireless and wired networks. However, its performance in wireless networks is often unsatisfactory due to issues such as bandwidth limitations and utility problems with lower network layers. The mobility effect further exacerbates TCP's performance, as it fails to distinguish between connection failure and congestion-induced connection loss. In response to this challenge, researchers have explored potential solutions and found that TCP FeW outperforms the existing TCP NewReno. Building upon this background, this paper aims to simulate and analyze the performance of TCP AFW and TCP FeW in an IEEE 802.11 network. The simulations conducted using ns2 in a limited environment with random mobile scenarios reveal that TCP AFW achieves a 1.12% higher throughput compared to FeW, even with minimal modifications.
Substitute to War: Questioning the Efficacy of Sanctions on Russia
Authors: Lawniczak Brent
Published: September 2023

Western nations enacted harsh sanctions against Russia after its 2022 invasion of Ukraine. However, sanctions are rarely successful and policy makers should not expect sanctions to coerce Russia into a withdrawal. This article examines several concepts including the instrumental effectiveness of sanctions, the significance of state identity, the pitfall of mirror imaging, and aspects of prospect theory as they relate to the effectiveness of sanctions. Additionally, the weakness of sanctions used for moral signaling and the notion of sanctions as an act of war are considered. Recommendations are offered should policy makers continue to view economic sanctions as an attractive policy choice.
A randomized controlled trial to investigate the effects of incentives on tuberculosis testing rates in rural Philippines
Authors: Ng Hei-Yue , Pang Sharon Sze Lu , Lee Siwon , Lim Krisha , Lau Lincoln L
Published: September 2023

Despite efforts to eliminate tuberculosis (TB), the Philippines continues to have one of the highest TB incidence rates in the world. Individuals of low socio-economic status are often at disproportionately high risk of contracting TB. However, TB testing rates remained low among this population, resulting in high disease transmission and deaths. Limited literature exists on interventions aimed at improving TB testing rates among populations living in extreme poverty in the Philippines. Therefore, this clustered randomized controlled trial (RCT) will investigate the effects of incentives for enhancing TB testing in rural health units (RHU) in the Philippines. The study will be conducted as part of the TB testing program led by International Care Ministries (ICM), a non-profit organization operating in the Philippines.
Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study
Authors: Nickl-Jockschat Thomas , Sharkey Rachel , Bacon Chelsea , Peterson Zeru , Rootes-Murdy Kelly , Salvador Raymond , Pomarol Edith , Karuk Andriana , Homan Philipp , Ji Ellen , Omlor Wolfgang , Homan Stephanie , Georgiadis Foivos , Kaiser Stefan , Kirschner Matthias , Ehrlich Stefan , Dannlowski Udo , Grotegerd Dominik , Goltermann Janik , Meinert Susanne , Kircher Tilo , Stein Frederike , Brosch Katharina , Krug Axel , Nenadic Igor , Sim Kang , Piras Fabrizio , Banaj Nerisa , Sponheim Scott , Demro Caroline , Ramsay Ian , King Margaret , Quidé Yann , Green Melissa , Nguyen Dana , Preda Adrian , Calhoun Vince , Turner Jessica , Erp Theo van , Spalletta Gianfranco
Published: September 2023

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.
Predictive Values of an Immunological Fecal Occult Blood Test for the Diagnosis of Colorectal Cancer at the Colonoscopy in Yaounde (Cameroon)
Authors: Jovanka Tchuitcheu Ulrich , Wilson NDJITOYAP NDAM Antonin , Winnie Bekolo Nga , Paule Ngogang Marie , Paul Talla , Isabelle Dang Babagna , Magloire Biwole Sida
Published: September 2023

Introduction: Colorectal cancer (CRC) is a public health problem in the world. The gold standard test for an early diagnostic is a colonoscopy with a histological exam of the lesion. This is invasive and expensive and few available in rural areas of sub-Saharan African (SSA) countries. The immunological fecal occult blood (iFOB) test have shown its predictive value for the screening of the CRC in west. But its interest in SSA is few studied. It could be altered by the other causes lower digestive bleeding such as worm digestive infections. The aim of this study was to highlight the performance of an iFOB test for the diagnosis of CRC regarding the colonoscopy in SSA area.
Methodology: We conducted an analytical cross-sectional study in two digestive endoscopic centers of Yaoundé (Cameroon) from the 1st July to the 31 November 2022. Patients presenting an indication for colonoscopy without any visible digestive bleeding were included. We collected sociodemographic data and clinical signs. Then, these patients gave their consent and underwent a qualitative immunologic occult test through the iFOB test before the colonoscopy. Data were analyzed using SPSS version 23.0 software. The performance of the iFOB test for the diagnosis of CRC at colonoscopy was evaluated in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV).
Results: We registered 103 patients during the period. They were predominantly male with a sex ratio of 1.7. The median age was 52 ± 13 years (range 1 – 84 years). The most common colonoscopy lesions were polyps in 23 patients (22.3%), CRC in 17 patients (16.5%) and hemorrhoids in 15 patients (14.6%). Patients testing positive for iFOB test accounted for 43.7% (45 patients). Among these patients, 31.1% (14 patients) had a CRC. The Se of the occult blood test for CRC detection was calculated to be 82.3% (CI: 56.7 - 96.2); the Sp was 63.9% (CI: 53 - 74); the PPV was 31.1% (CI: 24 - 39) and the NPV was 94.8% (CI: 86.6 - 98.1).
Conclusion: the iFOB test has a good NPV, but a poor PPV for the diagnosis of CRC in our study.
Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2+/- female mice
Authors: Hou Sheng-Tao , Ju Jun , Li Xuanyi , Yang Xinyi , Du Jun , Men Siqi , Liu Bo , Zhang Zhenyu , Zhong Haolin , Mai Jinyuan , Wang Yizheng
Published: September 2023

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2+/− female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2+/− female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2+/− female mice. Elevated adenosine functioned through its cognate A1 receptor to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1 receptor using a specific antagonist DPCPX or knockdown the A1 receptor in the PFC using an shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical cause for ameliorating social novelty deficit through the reduction of excitatory neurotransmission by the 40 Hz light flicker. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.
Knowledge and Compliance to Hand Hygiene Among Anesthesiologists in the Operation Room in Sudan 2022
Authors: Khalel Farah , Abdalla Eltayeb , Hassabo Mohammed
Published: September 2023

Objectives
This study aims to assess anesthesiology registrars’ knowledge and compliance with Hand hygiene strategies in the operation room and ICU in Sudan in 2022.
Materials and Methods
This was a descriptive cross-sectional study conducted among anesthesiology registrars registered in the Sudanese Council of Anaesthesia and Intensive Care. Data was collected by the researcher using a self-administered Google form questionnaire assessing knowledge about patient prevention, self-protection, alcohol-based rubbing, hand washing using soap and water, and compliance with the WHO 5 moments hand hygiene practice, then analyzed by SPSS V 28 software.
Results
The study included 150 anesthesiology registrars with a mean age of 31 ± 4 years and a female majority of 67%. Overall, the majority 88% have a fair knowledge regarding hand hygiene, 12% have poor knowledge, and 65% were compliant with all the recommended 5 moments of hand hygiene. Analysis of Factors affecting participants’ compliance with WHO 5 moments revealed that only experience was associated with the participants’ compliance.
Conclusion
Many gaps in knowledge about hand hygiene were identified regarding patients and self-protection, and hand washing and rubbing, thus, anesthesiology registrars had poor to fair knowledge regarding hand hygiene. While 65% of them are compliant with the WHO 5 Moments hand hygiene. Compliance with the WHO 5 Moments hand hygiene was associated with participants' experience.
A pilot trial of the effect of bone antiresorptive agents on bone turnover markers in critically ill women
Authors: Orford Neil R , Bone Allison , Kotowicz Mark A , Bailey Michael , Pasco Julie A , Maiden Matthew , Kakho Nima , Cattigan Claire , Nichonghaile Martina , Jones Claire , Hodgson Carol , Nair Priya , Center Jacqueline , Bellomo Rinaldo
Published: September 2023

Rationale:
Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established.
Objectives:
Examine the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater.
Methods:
Women aged 50 years or greater admitted to an intensive care unit for at least 24 hours were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for one year.
Measurements and Main Results:
We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (+40%), compared to an increase of 26% (+ 55%) observed with placebo (absolute difference -69%, 95% CI -127% to -11%), p=0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded.
Conclusions:
In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.
Trial registration: ACTRN12617000545369, registered 18th April 2017
Own price elasticities of the demand for sugar-sweetened beverages in Bangladesh
Authors: Huque Rumana , Azad Abul Kalam , Ahmed Nasiruddin
Published: September 2023

Background: Consumption of sugar-sweetened beverages (SSB) is a major public health problem globally. Increasing the price of SSBs through taxation is an effective tool to reduce SSB consumption. Price-elasticity estimates are useful in measuring the effect of taxation on consumption. We estimated the own price elasticities of demand for SSBs in Bangladesh, which will inform how SSB taxes could affect behaviour.
Methods: We used Household Income and Expenditure Survey (HIES) 2016 data, which is a nationally representative dataset on the household level across the country and is conducted using the stratified random sampling method. Deaton’s method is generally used to estimate the price elasticities for household-level data where data on prices are not available. We also employed Deaton’s method to estimate the price elasticities for SSBs in Bangladesh.
Results: We found that the own price elasticity for SSBs varied between -0.53% to -1.17% by types of SSBs in Bangladesh. The price elasticity for soft drinks was −1.17, indicating that if the price of soft drinks increases by 10% via taxes, the quantity consumed of these beverages would reduce by 11.7%.
Conclusion: This is the first study that estimates the own price elasticities of demand for SSBs in Bangladesh. Our results suggest raising SSB prices through increased taxation in order to reduce SSB consumption and ensure public health gains in Bangladesh.
The PI4K2A positively regulates the synthesis of milk fat in cows, promotes the proliferation of bovine mammary epithelial cells, and inhibits their apoptosis
Authors: Mu Tong , Hu Honghong , Feng Xiaofang , Wang Chuanchuan , Zhang Juan , Sun Zhihong , Gu Yaling
Published: September 2023

Background: Milk fat is the most important and energy-rich substance in milk. It is crucial to study the theory and pathways of milk fat synthesis and its regulation in dairy cows for the study of lactation biology. However, the current identification of valuable candidate genes affecting milk fat is limited.
Method: This study uses real-time quantitative PCR (qRT-PCR) technology to perform tissue expression profile analysis on 15 candidate differentially expressed genes related to milk fat metabolism obtained from our previous transcriptome sequencing and weighted gene co-expression network analysis (WGCNA), to determine the key candidate genes affecting milk fat synthesis in dairy cows. Investigate the specific regulatory mechanisms of key candidate genes in cow milk fat metabolism using overexpression (adenovirus) and interference techniques (lentivirus).
Results: The results showed that the expression level of PI4K2A gene in milk gland tissue was significantly higher than that in small intestine, liver, kidney, heart, and ovary (P < 0.05). Compared with other genes, the expression of PI4K2A in mammary gland tissue and bovine mammary epithelial cells (BMECs) was also higher and more stable. Ultimately, we identified PI4K2A as the key candidate gene responsible for regulating milk fat synthesis in dairy cows, and it plays a vital role in the cytoplasm of BMECs. Afterwards, we constructed the adenovirus overexpression vector and lentivirus interference vector for the PI4K2A gene, and combined quantitative real-time PCR (qRT-PCR) and western blot (WB) techniques to detect the effects of overexpressing and interfering with the PI4K2A gene on lipid metabolism in BMEC. The results indicate that the PI4K2A gene plays a positive regulatory role in the fatty acid (FA) transport process involved in milk fat synthesis in cows (P < 0.05). Upon further examination of triglycerides (TAG), cholesterol, and lipid droplet content in BMECs, we found that PI4K2A also has a positive regulatory effect on bovine milk fat synthesis (P < 0.05). The results obtained from EdU and apoptosis kit detection indicated that the PI4K2A gene positively regulated BMECs proliferation (P < 0.05) while negatively regulating their apoptosis process (P < 0.05).
Conclusions: This study offers valuable genetic marker information for precise molecular breeding of milk component traits in dairy cows, with potential implications for mammary gland wound healing and treatment of mammary gland-related diseases.
A simple but high effective specimen preparation for DNA extraction of Mycobacterium tuberculosis and its clinical application in quantitative-PCR determination of tuberculosis infection
Authors: Yuan Ren-bin , Liu Shuang , Cui Yu-qian , Cao Min , Zhuo Hui , Wang Tai-song , Xie Xu-chao , Zhang Miao-yu , Xu He , Wan Fan , He Qing
Published: September 2023

Background：In the recent few years, there is an ongoing outbreak of tuberculosis worldwide. Molecular diagnosis based on genomic amplification is a rapid and reliable method for early detection of tuberculosis infection. However, the quality and quantity of nucleic acid of Mycobacterium tuberculosis (MTB) extracted from different human specimens is still a bottleneck for molecular analysis because of the difficulty associated with breaking cell walls of MTB.
Methods：In this study, new specimens handling methods including Dounce homogenizer with a loose pestle and a tight pestle, compared with a conventional procedure consisted of sodium hydroxide, were applied for DNA isolation from human samples (sputum and pleural effusion) with or without MTB, and real time quantitative PCR (RT-qPCR) were evaluated DNA recovery, sensitivity and specificity for early and accurate diagnosis of tuberculosis infection.
Results：45 patients infected with tuberculosis and 56 normal controls were enrolled. With specimens handling with both the tight pestle and loose pestle of Dounce homogenizer, MTB DNA was recovered about 300 -104 times than traditional specimen pretreated method and 83.67%-100% tuberculosis infections could be better detected. The new DNA extraction methods were also performed excellent in plural effusion with detection rate in the range of 85.71%-90.47%. The relative lower specificity (80.55%-92.31%) was also well explained by follow-up. RT-qPCR handling with D-Tight data expanding with another 209 suspicious TB individuals (164 diagnosed with TB infection and 45 diagnosed with non-TB infection) showed a high sensitivity (97.47%, taken clinical diagnosis as golden standard) with no significant diverse between TB treated group and TB non-treated group (96.30% VS 98.08%).
Conclusions： The results demonstrates that Dounce homogenizer could offer high quality and quantity MTB DNA to RT-qPCR determination of MTB infection.
A simple and rapid preparation of smooth muscle myosin 2 for the electron microscopic analysis
Authors: Bharda Anahita , Jung Hyun Suk
Published: September 2023

There has been an increase in the demand for purified protein as a result of recent developments in the structural biology of myosin 2. Although promising, current practices in myosin purification are usually time-consuming and cumbersome. The reported increased actin to myosin ratio in smooth muscles adds to the complexity of the purification process. Present study outlines a streamlined approach to isolate smooth muscle myosin 2 molecules from actomyosin suspension of chicken gizzard tissues. The procedure entails treating actomyosin for a brief period with actin-binding peptide phalloidin, followed by co-sedimentation and short column size exclusion chromatography. Typical myosin molecule with heavy and light chains and approximately 95% purity was examined using gel electrophoresis. Negative staining electron microscopy and image processing showed intact 10S myosin 2 molecules, proving that phalloidin is effective at eliminating majority of actin in the form of F-actin without dramatic alteration in the structure of myosin. The entire purification discussed here can be completed in a few hours, and further analysis can be done the same day. Thus, by offering quick and fresh supplies of native myosin molecules suited for structural research, specially cryo-electron microscopy, this innovative approach can be adapted to get around the drawbacks of time-intensive myosin purifying processes.
Preservation of pulmonary branch of vagus nerve in three-dimensional thoracoscopic radical resection of lung cancer: a retrospective study
Authors: Huang Wencong , Yang Jiantian , Chen Huiwen , Li Peijian , Wei Wei
Published: September 2023

Background Preservation of the pulmonary branch of the vagus nerve during systematic dissection of mediastinal lymph nodes in radical resection of lung cancer was studied to explore its role in reducing postoperative complications.Methods The clinical data of 80 patients who underwent three-dimensional thoracoscopic radical resection of lung cancer in the Department of Thoracic Surgery of Huizhou Municipal Central Hospital from 2020 to 2022 were analyzed. The patients were divided into two groups according to whether the pulmonary branch of the vagus nerve was retained during intraoperative carinal lymph node dissection: those in whom the pulmonary branch of the vagus nerve was retained and those in whom the pulmonary branch of the vagus nerve was not retained. The operative duration, first postoperative defecation time, chest tube duration, total chest drainage volume, average pain intensity during the first 5 days, incidence of postoperative pneumonia, and postoperative hospitalization duration were compared between the two groups.Results There was no significant difference in the first postoperative defecation time between the two groups (P > 0.05). However, there were statistically significant differences in the operative duration, chest tube duration, total chest drainage volume, average pain intensity during the first 5 days, white blood cell count and procalcitonin level on postoperative days 1 and 5, and postoperative hospitalization duration between the two groups (P < 0.05).Conclusion Preserving the pulmonary branch of the vagus nerve during carinal lymph node dissection in three-dimensional thoracoscopic radical resection of lung cancer can reduce postoperative complications.
Dissipation, residues and evaluation of processing factor for spirotetramat and its formed metabolites during kiwifruit growing, storage and processing
Authors: Tian Fajun , Qiao Chengkui , Wang Caixia , Pang Tao , Guo Linlin , Li Jun , Pang Rongli , Xie Hanzhong
Published: September 2023

Spirotetramat is widely used around the world to control sucking pests and may form in agricultural products. In the current study, the dissipation, residues and evaluation of processing factor (PF) for spirotetramat and its formed metabolites were investigated during kiwifruit growing, storage and processing. The residue analysis method was established based on high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) combined with a QuEChERS method to detect the residues of spirotetramat and its metabolites in kiwifruit and its processed products. The method provided recoveries of 74.7 − 108.7%, and the relative standard deviations (RSDs) were 0.6–13.1%. The residues dissipated following the first-order kinetics with a half-life of 9.90–10.34 days in the field and 24.75–30.13 days during storage. Residues of spirotetramat and its formed metabolites in kiwifruit would not pose dietary risk to consumers. Moreover, the peeling and fermentation was the highest removal efficiency for the spirotetramat and its formed metabolites residues during prosessing. The PF values calculated after each individual process were < 1, indicating significant reduction of residues in different processing processes of kiwifruit. The spirotetramat was degraded during kiwifruit wine-making process with half-lives of 3.36–4.91 days. B-enol and B-keto were the main metabolites detected in kiwifruit and its processed products. This study revealed the residues of spirotetramat and its formed metabolites in kiwifruit growing, storage and processing, which helps provide reasonable data for studying the dietary risk factors of kiwifruits and products.
Experimental and Numerical Mudflows Modeling for Runout and Deposition Height Assessmen
Authors: Muñoz Fredy , Vega Johnny , Hidalgo César
Published: September 2023

Mudflows are natural phenomena starting from landslides and presenting high impact when they occur. They generate great catastrophes in their path because most of the time there is no indication prior to the failure that triggers them. Understanding how mud is transported is of great importance in infrastructure projects that coincide with hillside areas due to the high risk of occurrence of this phenomenon by cause of the high slopes, which can involve great risks and produce disasters that involve great costs. This work presents the evaluation of mudflows, from the implementation of a laboratory scale experiment in a consistometer with its calibration and validation from numerical models to estimate rheological parameters of the material. Tests were also carried out in an open channel in the laboratory, based on the data previously obtained considering the behavior of the material as a both Newtonian fluid and non-Newtonian fluid. The experiment considered a channel with dimensions of 3 m long, 0.5 m high and 0.7 m wide with slope control, and a mud composition of silty material with 60% moisture. The tests were conducted with slopes of 5%, 10%, 15% and 20%. The numerical models were carried out in ANSYS FLUENT software. In addition, the calibration data of the numerical model were used for a real case study, simulating the slip flow occurred in Yangbaodi, in the southeast of China, occurred on September 18, 2002. The results of the numerical models were compared with the experimental results and show that these have a great capacity to reproduce what is observed in the laboratory when the material is considered as a non-Newtonian fluid. The model reproduced in an appropriate way the movement of the flow at laboratory scale, and for the aforementioned case study, some differences in the final length of deposition were noticed, achieving interesting results that lead the use of the calibrated model towards the estimation of risks due to the mudflow occurrence.
The impact of an increased Fibrosis-4 index and the severity of hepatic steatosis on mortality in diabetes patients
Authors: Ma Xiaoyan , Zhu Yixuan , Yeo Yee Hui , Fan Zhiwen , Xu Xiaoming , Rui Fajuan , Ni Wenjing , Gu Qi , Tong Xin , Yin Shengxia , Qi Xiaolong , Shi Junping , Wu Chao , Li Jie
Published: September 2023

Background & aims: Data on the effects of liver fibrosis and hepatic steatosis on outcomes in diabetic patients are limited. Therefore, we investigated the predictive value of the fibrosis and the severity of hepatic steatosis for all-cause mortality in diabetes patients.
Methods: A total of 1,903 patients with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) dataset were enrolled. Presumed hepatic fibrosis was evaluated with Fibrosis-4 index (FIB-4). The mortality risk and corresponding hazard ratio (HR) were analyzed with the Kaplan-Meier method and multivariable Cox proportional hazard models.
Results: Over a median follow-up of 19.4 years, all-cause deaths occurred in 69.6%. An FIB-4 ≥1.3 was an independent predictor of mortality in diabetic patients (HR: 1.198, 95% confidence interval [CI]: 1.054-1.361, p =0.006). Overall, an FIB-4 ≥1.3 without moderate-severe steatosis increased the mortality risk (HR: 1.277; 95%CI: 1.077-1.513, p =0.005). The similar results were found in diabetes patients with metabolic dysfunction-associated fatty liver disease (MAFLD) (HR: 1.457; 95%CI: 1.045-2.032, p =0.027), metabolic syndrome (MetS) (HR: 1.343; 95%CI: 1.051-1.716, p =0.019) or abdominal obesity (HR: 1.325; 95%CI: 1.048-1.674, p=0.019).
Conclusions: Liver fibrosis, as estimated by FIB-4, may serve as a more reliable prognostic indicator for diabetic patients than hepatic steatosis. Diabetes patients with an FIB-4 ≥1.3 without moderate-severe steatosis had a significantly increased all-cause mortality risk. These findings highlight the importance of identifying and monitoring those patients, as they may benefit from further evaluation and risk stratification.
Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS Short title: CYP21A2 genotyping using MALDI-TOF MS
Authors: Yin Xiaoshan , Lin Yiming , Zhang Ting , Miao Haixia , Hu Lingwei , Hu Zhenzhen , Zhou Dou , Wu Benqing , Huang Xinwen
Published: September 2023

Background
Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates.
Methods
This study aimed to develop a novel MALDI-TOF MS assay that can identify common variants and deletions of CYP21A2 in the Chinese population.
Results
Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two CYP21A2 variants were detected in 30 patients and one CYP21A2 variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct CYP21A2 variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C > G (37.84%), followed by c.518T > A (21.62%) and exon 1–7 deletion (17.57%).
Conclusion
We have developed a high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of CYP21A2. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.
Clinical profile and parameters of patients infected with HBV and co-infected with HDV in Western Amazon
Authors: Silva Eugênia Castro e , Roca Tárcio Peixoto , Passos-Silva Ana Maísa , Borzacov Lourdes Maria Pinheiro , Oliveira Adrhyan Araújo Silva , Queiroz Jackson Alves Silva , Salcedo Juan Miguel Villalobos , Vieira Deusilene
Published: September 2023

Background
Hepatitis Delta represents an even greater risk in the progression of advanced liver disease compared with HBV and is related to rapid progression to liver cirrhosis and HCC. The exact mechanism that determines the spontaneous clearance of delta virus or its progression to fibrosis and cirrhosis remains unknown. In this scenario, studies on the influence of virological, immunological and genetic aspects related to clinical evolution in chronic carriers of HBV and HDV are still scarce, especially in the Amazon region. Therefore, this study aimed to analyze the clinical profile of infected and co-infected individuals in the Western Amazon.
Methods
The study was carried out at the Specialized Outpatient Clinic for Viral Hepatitis belonging to the Centro de Pesquisa em Medicina Tropical de Rondônia/CEPEM. 100 individuals were included, stratified into two groups: 50 with hepatitis B virus and 50 co-infected with hepatitis Delta virus.
Results
The overall mean age was 48 ± 10.38 years. For the HBV-positive and HDV-positive groups, 66% (33/50) and 54% (27/50) were men and 56% (28/50) and 58% (29/50) were on antiviral treatment, respectively. Among the HBV immune-active carriers, there was a predominance of men, high levels of HBV-DNA, thrombocytopenia and high levels of ALT and AST. HDV carriers with detectable HDV-RNA demonstrated predominance of thrombocytopenia and high levels of ALT and AST. Comparative analysis between patients with HBV and co-infected with HDV shows significant differences in terms of age, HBV viral load levels, platelet levels and albumin levels.
Conclusion
Thrombocytopenia, hypoalbuminemia, hepatomegaly, splenomegaly and advanced fibrosis were more prevalent in individuals infected with HDV compared to those monoinfected with HBV and may be important markers in differentiating the different infections. Patients with detectable HDV RNA also showed significant changes in biomarkers compared to undetectable patients, suggesting a worse prognostic effect in this group.
Liquid plasma induces necroptosis without inflammatory responses in head and neck cancer cells
Authors: Choi Jae Hoon , Kim Sungryeal , Lee Yun Snag , You Young Suk , Jang Jeon Yeob , Shin Yoo Seob , Kim Chul-Ho
Published: September 2023

Background
Several types of regulated cell deaths are known, including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Among these cell deaths, apoptosis is induced by many cancer therapeutic agents. In the case of resistance, however, induction of other regulated cell death, such as necroptosis, are required. Liquid plasma, which is prepared by treatment of non-thermal plasma to solution, induces various types of regulated cell death via reactive oxygen and nitrogen species.
Methods
Liquid plasma was generated by N2/Ar plasma treatment in culture medium (MEM, DMEM, or RPMI 1640) for 120 s per mL of medium (2 cm). Cell viability was determined using Cell Counting Kit-8 (CCK8) (Dojindo, NX653) and apoptosis was determined by TUNEL assay. TNF-α, CHX, and zVAD-fmk were used to induce necroptosis in HNSCC cells, and necroptosis inhibitors, such as Nec-1 (50 µM), GSK'872 (10 µM), and NSA (2 µM) were used to inhibit necroptosis. Statistical comparisons between groups were carried out using the student’s t-test.
Results
Here, we determined the type of cell death induced by liquid plasma in head and neck cancer (HNC) cells. Our results show that liquid plasma caused necroptosis in HNC cells, and peroxynitrite in the liquid plasma might be involved in the cell death. The levels of inflammation-related molecules, including NF-kB, IL-6, and mitochondrial antiviral signaling proteins, were elevated in HNC cells, and treatment of HNC cells with liquid plasma decreased their expression.
Conclusion
These results suggest that liquid plasma could be used to treat HNC by inducing necroptosis without inflammatory responses. In this study, we demonstrated that liquid plasma treatment may kill HNC cells without causing necroptosis-induced inflammation and inflammation-mediated diseases.
Longitudinal Influence of Dietary Fiber Intake and Ovarian Hormones on Body Mass Index Trajectories in Midlife Women: The Study of Women's Health Across the Nation
Authors: Luo Jing , Lin Song
Published: September 2023

Background
It is known that dietary fiber intake was inversely associated with risk of weight gain, while the association between dietary fiber intake and body mass index (BMI) trajectories over time is unclear. This study aimed to determine whether dietary fiber intake is associated with lower BMI trajectories and whether ovarian hormones would influence BMI trajectories in midlife women.
Methods
Participants were 2,706 multiracial/ethnic midlife women enrolled in a multi-site longitudinal menopause and aging study, Study of Women’s Health Across the Nation. Dietary intake was estimated using food frequency questionnaire with 103 food item at baseline. BMI and ovarian hormones were measured approximately annually from 1997 to 2008. Group-based trajectory modelling identified the trajectories of BMI and associations with time-varying ovarian hormones. The effect of dietary fiber intake (g/1000kcal·d) on BMI trajectories was examined using multinomial logistic regression.
Results
Participants had four distinct BMI trajectories: low BMI trajectory (30.4%), medium BMI trajectory (36.2%), high BMI BMI trajectory (22.9%), and very high BMI trajectory (10.5%). Each unit increase in dietary fiber intake (g/1000kcal·d) was less likely to be medium, high and very high BMI trajectories than low BMI trajectory. Compared to low BMI trajectory, daily dietary fiber intake 8-9g/1000kcal is the minimum requirement for the prevention of medium, high, and very high BMI trajectories. Women with dietary fiber intake exceeded 15g/1000kcal or 16g/1000cal per day have the lowest risk of medium and high BMI trajectories than low BMI trajectory, respectively. Of the time-varying covariates considered, higher total family income, drinking alcohol, higher quality of life, and serum estradiol, follicle-stimulating hormone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, was associated with a decrease BMI in almost all trajectories, while a positive relationship between testosterone and BMI was presented across all trajectory groups.
Conclusions
Higher fiber intake, especially 15–16 g/1000cal per day, was associated with lower BMI trajectories in midlife women. Health care providers need to evaluated women’s dietary intake, family economics, lifestyle, and ovarian hormones during midlife to monitor changes in these and BMI.
Machine-learning potentials for nanoscale simulations of deformation and fracture: example of TiB2 ceramic
Authors: Lin Shuyao , Casillas-Trujillo Luis , Tasnadi Ferenc , Hultman Lars , Mayrhofer Paul H. , Sangiovanni Davide , Koutná Nikola
Published: September 2023

Machine-learning interatomic potentials (MLIPs) offer a powerful avenue for simulations beyond length and timescales of ab initio methods. Their development for investigation of mechanical properties and fracture, however, is far from trivial since extended defects---governing plasticity and crack nucleation in most materials---are too large to be included in the training set. Using TiB2 as a model ceramic material, we propose a strategy for fitting MLIPs suitable to simulate mechanical response of monocrystals until fracture. Our MLIP accurately reproduces ab initio stresses and failure mechanisms during room-temperature uniaxial tensile deformation of TiB2 at the atomic scale (≈103 atoms). More realistic tensile tests (low strain rate, Poisson's contraction) at the nanoscale (≈104--106 atoms) require MLIP up-fitting, i.e. learning from additional ab initio configurations. Consequently, we elucidate trends in theoretical strength, toughness, and crack initiation patterns under different loading directions. To identify useful environments for further up-fitting, i.e., making the MLIP applicable to a wider spectrum of simulations, we assess transferability to other deformation conditions and phases not explicitly trained on.
Assembly of tight junction belts by surface condensation and actin elongation
Authors: Honigmann Alf , Sun Daxiao , Zhao Xueping , Wiegand Tina , Bartolucci Giacomo , Martin-Lemaitre Cecilie , Grill Stephan , Hyman Anthony , Weber Christoph
Published: September 2023

Tight junctions play an essential role in sealing tissues, by forming belts of adhesion strands around cellular perimeters. The formation of a tight junction occurs into two steps, initiation at cell-cell contacts, and elongation around the perimeter. Recent work has shown that nucleation is governed by condensation of scaffold proteins. However, the mechanisms by which condensates are spatially controlled to initiate at cell-cell contacts and elongate around cell perimeters remain unknown. Here, we combined cell biology, molecular reconstitution and thermodynamic modelling to show that belt formation is driven by a surface phase transition coupled to actin polymerization. Adhesion receptor oligomerization provides the signal for local surface condensation of ZO proteins. Surface condensates directly facilitate actin polymerization and filament bundling, which drives elongation of receptor-ZO-actin condensates into a junctional belt. We conclude that surface phase transitions provide a robust mechanism to locally control the position and shape of protein condensates.
Long-term decitabine/retinoic acid maintenance treatment in an elderly sAML patient with high-risk genetics
Authors: Javorniczky Nora Rebeka , Grishina Olga , Hund Inga , Pantic Milena , Pfeifer Dietmar , Schmoor Claudia , Thomas Johanna , Duyster Justus , Becker Heiko , Lübbert Michael
Published: September 2023

Elderly patients with AML ineligible for induction have dismal prognosis; hence disease stabilization is a primary treatment goal. This case of a 74-year-old patient with secondary AML receiving the combination of decitabine and ATRA (within the DECIDER trial, NCT00867672) demonstrates an above-average survival. The therapy administered over 52 cycles led to complete molecular and hematological remission and resulted in 5.3 years overall survival. Clonal evolution of the leukemic clone could be demonstrated using DNA sequencing methods. According to the literature this case constitutes the longest continued HMA exposure in an elderly AML patient ineligible for standard chemotherapy.
Malaria Parasite Classification from RBC Smears Using Lightweight Parallel Depthwise Separable CNN and Ridge Regression ELM by Integrating SHAP Techniques
Authors: Ahamed Md. Faysal , Nahiduzzaman Md. , Ayari Mohamed Arselene , Khandakar Amit , Islam S. M. Riazul
Published: September 2023

Malaria is a significant health concern worldwide, and early detection and accurate classification are essential for better treatment. This study proposes a new method that combines a lightweight parallel depth-wise separable convolutional neural network (LPDCNN) with a hybrid ridge regression extreme learning machine (RELM) to classify images of infected and uninfected patients' red blood cells (RBCs). We include a hybrid pre-processing step that uses contrast-limited adaptive histogram equalization (CLAHE) and Dilation operation to enhance image quality, reduce cell noise, and improve visual acuity. The LPDCNN extracts discriminative features efficiently with only 0.36 million parameters and 8 layers, minimizing computational complexity. The hybrid RELM model improves classification performance and replaces the traditional pseudoinverse of the ELM approach. Rigorous five-fold cross-validation (CV) for binary class classifications shows that the framework has impressive average precision, recall, f1, accuracy, and AUC scores of 99.86±0.08%, 99.88±0.084%, 99.84±0.089%, 99.85±0.071%, and 99.96±0.037%, respectively, surpassing state-of-the-art (SOTA) models. The proposed framework is exceptionally efficient, with an average training and testing time of 0.1376 and 0.00255 seconds, respectively. Additionally, the framework is integrated SHAP (Shapley Additive Explanations) to enhance interpretability, providing valuable insights into decision-making and instilling confidence in malaria diagnosis for real-world applications. This comprehensive approach holds promise in improving malaria diagnosis and patient outcomes worldwide.
Prognostic analysis of atrial fibrillation patients with acute cerebral infarction: a retrospective study of 330 cases over a 10-year period
Authors: Wang Hai-Xia , Zhang Nan , Wang Guo-Qiang , Huang Yong-Hua
Published: September 2023

Background:
The neurologic outcome of atrial fibrillation (AF) patients with acute ischemic stroke (AIS) is usually worse than those without AF. The aim of our study was to evaluate prognostic factors in AF-AIS.
Methods
We retrospectively collected information about AF-AIS patients admitted to our department from Jan. 2013 and Aug. 2023. According to the modified Rankin Scale (mRS) score at discharge, patients were divided into two groups: group A with favorable outcomes (mRS ≤ 2,) and group B with poor outcomes (mRS > 2).
Results
A total of 330 AF-AIS patients met the inclusion criteria, including 95 in group A and 235 in group B. The large-, medium- and small-infarct sizes were 45.5%, 31.5% and 23.0%, respectively. Intravenous alteplase thrombolysis (IV-rtPA) was prescribed to 69 patients. Parenchymal hemorrhage (PH) was present in 53 (16.1%) patients. The incidence of PH for patients with IV-rtPA was 34.8% (24/69), and 17.9% (45/251) for no-IV-rtPA patients. In univariate analysis, older age, higher NIHSS score and glucose, lower level of triglyceride, lager infarct size and PH were all associated with a poor outcome. No difference was found between the good and poor outcomes with IV-rtPA (18.9% vs. 21.7%, p = 0.578). In multivariate analysis, age (OR 1.059, 95% CI 1.024–1.094, p = 0.001), NIHSS score (OR 1.305, 95% CI 1.210–1.407, p < 0.001), infarct size (OR 2.485, 95% CI 1.018–6.062, p = 0.045), glucose (OR 1.994, 95% CI 1.011–3.933, p = 0.046) and PH (OR 4.130, 95% CI 1.303–13.092, p = 0.016) were independently associated with poor outcome. And, large infarct size (OR 3.786, 95% CI 1.912–7.459, p < 0.001), IV-rtPA (OR 4.904, 95% CI 2.452–9.808, p < 0.001), lower baseline level of triglyceride (OR 3.797, 95% CI 1.636–8.817, p = 0.002) and diabetes mellitus (OR 2.973, 95% CI 1.477–5.983, p = 0.002) were significantly associated with the development of PH.
Conclusion
The majority of AF-AIS patients had a poor outcome, which was independently associated with age, NIHSS score, infarct size, glucose and PH. IV-rtPA was related to an increased risk of PH and failed to improve overall short-term outcomes, especially for those with a large infarct size, a lower level of baseline triglyceride and a history of diabetes mellitus.
Evolution of protein domains and protein domain combinations provides insights into the origin and diversification of land plants
Authors: Xue Jia-Yu , Yang Cheng-Ao , Hu Shuai-Ya , Fan Hai-Yun , Shao Zhu-Qing , Dong Shanshan , Liu Yang , de Peer Yves Van
Published: September 2023

The authors have requested that this preprint be removed from Research Square.
Lebesgue spaces with variable exponent: some applications to the Navier-Stokes equations
Authors: Chamorro Diego , Vergara-Hermosilla Gaston
Published: September 2023

In this article we study some problems related to the incompressible 3D Navier-Stokes equations from the point of view of Lebesgue spaces of variable exponent. These functional spaces present some particularities that make them quite different from the usual Lebesgue spaces: indeed, some of the most classical tools in analysis are not available in this framework. We will give here some ideas to overcome some of the difficulties that arise in this context in order to obtain different results related to the existence of mild solutions for this evolution problem.