bluuebunny/crossref_metadata_2025_split huggingface dataset:
METTL3 suppresses anlotinib sensitivity by regulating m6A modification of FGFR3 in oral squamous cell carcinoma
Authors: Chen Jie , Li Shuai , Huang Zhexun , Cao Congyuan , Wang Anxun , He Qianting 
Published: September 2022

Abstract
Background
N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA, but there were few studies on its role in cancer drug sensitivity and resistance. Anlotinib has been proved to have effective antitumor effects in oral squamous cell carcinoma (OSCC) in our previous study. Here, we sought to investigate the treatment target of anlotinib and the function and mechanisms of m6A modification in regulating anlotinib effect in OSCC.

Methods
Anlotinib treatment in a dose-dependent manner, western blotting, qRT-PCR and cell lost-of-function assays were used to study the treatment target of anlotinib in OSCC. RNA m6A dot blot assays, the m6A MeRIP-seq and MeRIP-qPCR, RNA and protein stability assays were used to explore the m6A modification of the treatment target of anlotinib. Cell lost-of-function assays after METTL3 depletion were conducted to investigate the effect of m6A modification level on the therapeutic effect of anlotinib in OSCC. Patient-derived tumor xenograft (PDX) models and immunohistochemistry staining were performed to study the relationship of METTL3 and antitumor sensitivity of anlotinib in vivo.

Results
Anlotinib targeted FGFR3 in the treatment of OSCC and inhibited tumor cell proliferation and promoted apoptosis by inactivating the FGFR3/AKT/mTOR signaling pathway. METTL3 was identified to target and modify FGFR3 m6A methylation and then decrease the stability of mRNA. METTL3 expression level was related to the anlotinib sensitivity in OSCC cells in vitro and METTL3 knockdown promoted anlotinib sensitivity of OSCC cells by inhibiting the FGFR3 expression. PDX models samples furthermore showed that METTL3 and FGFR3 levels were tightly correlated with the anlotinib efficacy in OSCC.

Conclusions
In summary, our work revealed that FGFR3 was served as the treatment target of anlotinib and METTL3-mediated FGFR3 m6A modification played a critical function in the anlotinib sensitivity in OSCC.
Left colic artery diameter is an important factor affecting anastomotic blood supply in sigmoid colon cancer or rectal cancer surgery: a pilot study
Authors: Li Bo , Wang Jianan , Yang Shaohui , Shen Jie , Li Qi , Zhu Qiqi , Cui Wei 
Published: September 2022

Abstract
Background
Anastomotic blood supply is vital to anastomotic healing. The aim of this study was to demonstrate the effect of the left colic artery (LCA) on blood supply in the anastomotic area, explore the relationship between individual differences in the LCA and blood supply in the anastomotic area, and elucidate the relevant indications for LCA retention during radical resection for sigmoid or rectal cancer.

Method
Radical sigmoid or rectal cancer resection with LCA retention was performed in 40 patients with colorectal cancer who participated in this study. Systemic pressure, LCA diameter, and the distance from the root of the LCA to the root of the inferior mesenteric artery were measured and recorded. The marginal artery stump pressure in the anastomotic colon before and after the LCA clamping was measured, respectively.

Results
There is a significant difference between the marginal artery stump pressure before LCA ligation and after ligation (53.1 ± 12.38 vs 42.76 ± 12.71, p < 0.001). The anastomotic blood supply positively and linearly correlated with body mass index and systemic pressure. Receiver-operating curve analysis revealed that LCA diameter (area under the curve 0.971, cutoff 1.95 mm) was an effective predictor of LCA improving anastomosis blood supply. No relationship was found between the LCA root location and anastomotic blood supply.

Conclusion
Preserving the LCA is effective in improving blood supply in the anastomotic area, and larger LCA diameters result in a better blood supply to the anastomotic area.
Impact of parental chromosomal polymorphisms on the incidence of congenital anomalies and perinatal complications in a cohort of newborns conceived after ICSI + PGT-A
Authors: Rodriguez Freddy , Cruz Maria , Requena Antonio 
Published: September 2022

Abstract
Background
To assess the association between chromosomal polymorphisms (CPM) with congenital anomalies and perinatal complications in a cohort of newborns from couples undergoing intracytoplasmic sperm injection (ICSI), trophectoderm biopsy, and preimplantation genetic testing for aneuploidy (PGT-A).

Methods
A retrospective cohort of singletons conceived after ICSI, trophectoderm biopsy, and PGT-A cycles performed at IVIRMA clinics in Spain over 4 years was involved in the study. Newborns were classified according to the parental karyotype analysis: Group I: non-carriers, Group II: CPM carriers. Couples with chromosomal anomalies and instances when both partners were CPM carriers were excluded from the study. The groups were compared for several perinatal complications.

Results
There was a significant decrease in the number of NB with complications in the carrier group compared to the non-carriers (19.7% vs 31.9%, p = 0.0406). There were no statistical differences among the two groups regarding congenital anomalies, preterm birth, alterations in birth length and weight, cranial perimeter, Apgar test score, or sex ratio (p > 0.05).

Conclusions
Chromosomal polymorphisms appear to have no adverse effects on congenital anomalies or perinatal complications on newborns from ICSI + PGT-A cycles.
False gene and chromosome losses in genome assemblies caused by GC content variation and repeats
Authors: Kim Juwan , Lee Chul , Ko Byung June , Yoo Dong Ahn , Won Sohyoung , Phillippy Adam M. , Fedrigo Olivier , Zhang Guojie , Howe Kerstin , Wood Jonathan , Durbin Richard , Formenti Giulio , Brown Samara , Cantin Lindsey , Mello Claudio V. , Cho Seoae , Rhie Arang , Kim Heebal , Jarvis Erich D. 
Published: September 2022

Abstract
Background
Many short-read genome assemblies have been found to be incomplete and contain mis-assemblies. The Vertebrate Genomes Project has been producing new reference genome assemblies with an emphasis on being as complete and error-free as possible, which requires utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. A more thorough evaluation of the recent references relative to prior assemblies can provide a detailed overview of the types and magnitude of improvements.

Results
Here we evaluate new vertebrate genome references relative to the previous assemblies for the same species and, in two cases, the same individuals, including a mammal (platypus), two birds (zebra finch, Anna’s hummingbird), and a fish (climbing perch). We find that up to 11% of genomic sequence is entirely missing in the previous assemblies. In the Vertebrate Genomes Project zebra finch assembly, we identify eight new GC- and repeat-rich micro-chromosomes with high gene density. The impact of missing sequences is biased towards GC-rich 5′-proximal promoters and 5′ exon regions of protein-coding genes and long non-coding RNAs. Between 26 and 60% of genes include structural or sequence errors that could lead to misunderstanding of their function when using the previous genome assemblies.

Conclusions
Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the Vertebrate Genomes Project reference genomes.
Optimal@NRW: optimized acute care of nursing home residents using an intersectoral telemedical cooperation network — study protocol for a stepped-wedge trial
Authors: Brücken David , Unterkofler Jenny , Pauge Sophie , Bienzeisler Jonas , Hübel Christian , Zechbauer Sebastian , Rossaint Rolf , Greiner Wolfgang , Aufenberg Birthe , Röhrig Rainer , Bollheimer Leo Cornelius ,   Optimal@NRW Research Group, Stingl Julia , Ziefle Martina , Offermann Julia , Erdmann Pia , Eisert Albrecht , Koech Lea , Wilhelmy Saskia , Steinfeld Judith , Groß Dominik , Follmann Andreas , Czaplik Michael , Pollmanns Johannes , Krafft Thomas , Böbel Simone , Neuerer Maresa , Brokmann Jörg Christian 
Published: September 2022

Abstract
Background
Increasing life expectancy is associated with a growing number of people living in nursing homes, while the availability of outpatient medical care, especially from family doctors, is stagnating in this sector. Consequently, numerous and often avoidable, low-threshold hospitalizations of nursing home residents are observed. This results in unnecessary use of resources such as emergency services and emergency rooms as well as in potential health risks to the nursing home residents related to hospitalization. This study aims to improve this healthcare gap by implementing an intersectoral telemedicine approach.

Methods
Twenty-five nursing homes are participating and provided with telemedical equipment to perform teleconsultations. Additionally, an early warning system and a digital patient record system are implemented. Telephysicians based at RWTH Aachen University Hospital are ready to support the nursing homes around the clock if the family doctor or an emergency service practice is not available in time. Mobile non-physician practice assistants from the telemedicine centre can be dispatched to perform delegable medical activities. General practitioners and the medical emergency practices also have access to the telemedical infrastructure and the non-physician practice assistants.

Discussion
Optimal@NRW adds a telemedicine component to standard care — combining elements of outpatient and inpatient health care as well as emergency service practices — to enable timely medical consultation for nursing home residents in case of the development of an acute medical condition. In addition to optimized medical care, the goal is to reduce unnecessary hospital admissions. The intersectoral approach allows for the appropriate use of resources to match the individually needed medical treatment.

Trial registration
ClinicalTrials.govNCT04879537. Registered on May 10, 2021
Effect of anesthesia on the outcome of high-grade glioma patients undergoing supratentorial resection: study protocol for a pragmatic randomized controlled trial
Authors: Dong Jia , Wang Dexiang , Sun Huizhong , Zeng Min , Liu Xiaoyuan , Yan Xiang , Li Ruowen , Li Shu , Peng Yuming 
Published: September 2022

AbstractBackgroundHigh-grade glioma (HGG) is the most malignant brain tumor with poor outcomes. Whether anesthetic methods have an impact on the outcome of these patients is still unknown. Retrospective study has found no difference between intravenous and inhalation anesthesia on the overall survival (OS) of the HGG patients, however, intravenous anesthesia with propofol might be beneficial in a subgroup of patients with a Karnofsky Performance Status (KPS) Scale less than 80. Further prospective studies are needed to evaluate the results.MethodsThis is a single-centered, randomized controlled, parallel-group trial. Three hundred forty-four patients with primary HGG for tumor resection will be randomly assigned to receive either intravenous anesthesia with propofol or inhalation anesthesia with sevoflurane. The primary outcome is the OS of the patients within 18 months. Secondary outcomes include progression-free survival (PFS), the numerical rating scale (NRS) of pain intensity and sleep quality, the postoperative encephaloedema volume, complications, and the length of hospital stay of the patients.DiscussionThis is a randomized controlled trial to compare the effect of intravenous and inhalation anesthesia maintenance on the outcome of supratentorial HGG patients. The results will contribute to optimizing the anesthesia methods in these patients.Trial registrationClinicalTrials.govNCT02756312. Registered on 29 April 2016 and last updated on 9 Sep 2020
ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis—study protocol for an interventional randomised controlled trial
Authors: Crocombe Dominic , Ahmed Norin , Balakrishnan Indran , Bordea Ekaterina , Chau Marisa , China Louise , Corless Lynsey , Danquah Victoria , Dehbi Hakim-Moulay , Dillon John F. , Forrest Ewan H. , Freemantle Nick , Gear David Peter , Hollywood Coral , Hunter Rachael , Jeyapalan Tasheeka , Kallis Yiannis , McPherson Stuart , Munteanu Iulia , Portal Jim , Richardson Paul , Ryder Stephen D. , Virk Amandeep , Wright Gavin , O’Brien Alastair 
Published: September 2022

Abstract
Background
Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites.

Methods
The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients’ health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events.

Discussion
This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis.

Trial registration
ClinicalTrials.gov NCT043955365. Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central – Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).
Influence of landscape heterogeneity on entomological and parasitological indices of malaria in Kisumu, Western Kenya
Authors: Otambo Wilfred Ouma , Onyango Patrick O. , Wang Chloe , Olumeh Julius , Ondeto Benyl M. , Lee Ming-Chieh , Atieli Harrysone , Githeko Andrew K. , Kazura James , Zhong Daibin , Zhou Guofa , Githure John , Ouma Collins , Yan Guiyun 
Published: September 2022

AbstractBackgroundIdentification and characterization of larval habitats, documentation ofAnophelesspp. composition and abundance, andPlasmodiumspp. infection burden are critical components of integrated vector management. The present study aimed to investigate the effect of landscape heterogeneity on entomological and parasitological indices of malaria in western Kenya.MethodsA cross-sectional entomological and parasitological survey was conducted along an altitudinal transect in three eco-epidemiological zones: lakeshore along the lakeside, hillside, and highland plateau during the wet and dry seasons in 2020 in Kisumu County, Kenya. Larval habitats forAnophelesmosquitoes were identified and characterized. Adult mosquitoes were sampled using pyrethrum spray catches (PSC). Finger prick blood samples were taken from residents and examined for malaria parasites by real-time PCR (RT-PCR).ResultsIncreased risk ofPlasmodium falciparuminfection was associated with residency in the lakeshore zone, school-age children, rainy season, and no ITNs (χ2 = 41.201,df = 9,P < 0.0001). Similarly, lakeshore zone and the rainy season significantly increasedAnophelesspp. abundance. However, house structures such as wall type and whether the eave spaces were closed or open, as well as the use of ITNs, did not affectAnophelesspp. densities in the homes (χ2 = 38.695,df = 7,P < 0.0001).Anopheles funestus(41.8%) andAn. arabiensis(29.1%) were the most abundant vectors in all zones. Sporozoite prevalence was 5.6% and 3.2% in the two species respectively. The lakeshore zone had the highest sporozoite prevalence (4.4%, 7/160) and inoculation rates (135.2 infective bites/person/year). High larval densities were significantly associated with lakeshore zone and hillside zones, animal hoof prints and tire truck larval habitats, wetland and pasture land, and the wet season. The larval habitat types differed significantly across the landscape zones and seasonality (χ2 = 1453.044,df = 298,P < 0.0001).ConclusionThe empirical evidence on the impact of landscape heterogeneity and seasonality on vector densities, parasite transmission, andPlasmodiuminfections in humans emphasizes the importance of tailoring specific adaptive environmental management interventions to specific landscape attributes to have a significant impact on transmission reduction.Graphical abstract
Species-specific climate Suitable Conditions Index and dengue transmission in Guangdong, China
Authors: Lu Xinting , Bambrick Hilary , Frentiu Francesca D. , Huang Xiaodong , Davis Callan , Li Zhongjie , Yang Weizhong , Devine Gregor J. , Hu Wenbiao 
Published: September 2022

Abstract
Background
Optimal climatic conditions for dengue vector mosquito species may play a significant role in dengue transmission. We previously developed a species-specific Suitable Conditions Index (SCI) for Aedes aegypti and Aedes albopictus, respectively. These SCIs rank geographic locations based on their climatic suitability for each of these two dengue vector species and theoretically define parameters for transmission probability. The aim of the study presented here was to use these SCIs together with socio-environmental factors to predict dengue outbreaks in the real world.

Methods
A negative binomial regression model was used to assess the relationship between vector species-specific SCI and autochthonous dengue cases after accounting for potential confounders in Guangdong, China. The potential interactive effect between the SCI for Ae. albopictus and the SCI for Ae. aegypti on dengue transmission was assessed.

Results
The SCI for Ae. aegypti was found to be positively associated with autochthonous dengue transmission (incidence rate ratio: 1.06, 95% confidence interval: 1.03, 1.09). A significant interaction effect between the SCI of Ae. albopictus and the SCI of Ae. aegypti was found, with the SCI of Ae. albopictus significantly reducing the effect of the SCI of Ae. aegypti on autochthonous dengue cases. The difference in SCIs had a positive effect on autochthonous dengue cases.

Conclusions
Our results suggest that dengue fever is more transmittable in regions with warmer weather conditions (high SCI for Ae. aegypti). The SCI of Ae. aegypti would be a useful index to predict dengue transmission in Guangdong, China, even in dengue epidemic regions with Ae. albopictus present. The results also support the benefit of the SCI for evaluating dengue outbreak risk in terms of vector sympatry and interactions in the absence of entomology data in future research.

Graphical Abstract
Biochemical and clinical markers of endothelial dysfunction do not outweigh traditional risk factors for the presence of diabetic retinopathy in patients with type 1 diabetes
Authors: Matheus Alessandra Saldanha de Mattos , da Matta Maria de Fátima Bevilacqua , Clemente Eliete Leão Silva , Rodrigues Maria de Lourdes Guimarães , Valença Débora Cristina Torres , Drummond Karla Rezende Guerra , Gomes Marília Brito 
Published: September 2022

Abstract
Background
This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D).

Methods
Patients aged ≥ 12 years completed a clinical–epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays.

Results
Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6–15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI.

Conclusions
In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.
Conditional reduction of the loss value versus reinforcement learning for biassing a de-novo drug design generator
Authors: Chadi Mohamed-Amine , Mousannif Hajar , Aamouche Ahmed 
Published: September 2022

AbstractDeep learning has demonstrated promising results in de novo drug design. Often, the general pipeline consists of training a generative model (G) to learn the building rules of valid molecules, then using a biassing technique such as reinforcement learning (RL) to focus G on the desired chemical space. However, this sequential training of the same model for different tasks is known to be prone to a catastrophic forgetting (CF) phenomenon. This work presents a novel yet simple approach to bias G with significantly less CF than RL. The proposed method relies on backpropagating a reduced value of the cross-entropy loss used to train G according to the proportion of desired molecules that the biased-G can generate. We named our approach CRLV, short for conditional reduction of the loss value. We compared the two biased models (RL-biased-G and CRLV-biased-G) for four different objectives related to de novo drug design.CRLV-biased-G outperformed RL-biased-G in all four objectives and manifested appreciably less CF. Besides, an intersection analysis between molecules generated by the RL-biased-G and the CRLV-biased-G revealed that they can be used jointly without losing diversity given the low percentage of overlap between the two to further increase the desirability. Finally, we show that the difficulty of an objective is proportional to (i) its frequency in the dataset used to train G and (ii) the associated structural variance (SV), which is a new parameter we introduced in this paper, calling for novel exploration techniques for such difficult objectives.