bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of algorithms for identifying patients in a German claims database: learnings from a lung cancer case
Authors: Neugebauer Sina , Griesinger Frank , Dippel Sabine , Heidenreich Stephanie , Gruber Nina , Chruscz Detlef , Lempfert Sebastian , Kaskel Peter 
Published: June 2022

Abstract
Background
The analysis of statutory health insurance (SHI) data is a little-used approach for understanding treatment and care as well as resource use of lung cancer (LC) patients in Germany. The aims of this observational, retrospective, longitudinal analysis of structured data were to analyze the healthcare situation of LC patients in Germany based on routine data from SHI funds, to develop an algorithm that sheds light on LC types (non-small cell / NSCLC vs. small cell / SCLC), and to gain new knowledge to improve needs-based care.

Methods
Anonymized billing data of approximately four million people with SHI were analyzed regarding ICD-10 (German modification), documented medical interventions based on the outpatient SHI Uniform Assessment Standard Tariff (EBM) or the inpatient Operations and Procedure Code (OPS), and the dispensing of prescription drugs to outpatients (ATC classification). The study included patients who were members of 64 SHI funds between Jan-1st, 2015 and Dec-31st, 2016 and who received the initial diagnosis of LC in 2015 and 2016.

Results
The analysis shows that neither the cancer type nor the cancer stage can be unambiguously described by the ICD-10 coding. Furthermore, an assignment based on the prescribed medication provides only limited information: many of the drugs are either approved for both LC types or are used off-label, making it difficult to assign them to a specific LC type. Overall, 25% of the LC patients were unambiguously identifiable as NSCLC vs SCLC based on the ICD-10 code, the drug therapy, and the billing data.

Conclusions
The current coding system appears to be of limited suitability for drawing conclusions about LC and therefore the SHI patient population. This makes it difficult to analyze the healthcare data with the aim of gathering new knowledge to improve needs-based care. The approach chosen for this study did not allow for development of a LC differentiation algorithm based on the available healthcare data. However, a better overview of patient specific needs could make it possible to modify the range of services provided by the SHI funds. From this perspective, it makes sense, in a first step, to refine the ICD-10 system to facilitate NSCLC vs. SCLC classification.
Transcriptomic evidence for visual adaptation during the aquatic to terrestrial metamorphosis in leopard frogs
Authors: Schott Ryan K. , Bell Rayna C. , Loew Ellis R. , Thomas Kate N. , Gower David J. , Streicher Jeffrey W. , Fujita Matthew K. 
Published: June 2022

Abstract
Background
Differences in morphology, ecology, and behavior through ontogeny can result in opposing selective pressures at different life stages. Most animals, however, transition through two or more distinct phenotypic phases, which is hypothesized to allow each life stage to adapt more freely to its ecological niche. How this applies to sensory systems, and in particular how sensory systems adapt across life stages at the molecular level, is not well understood. Here, we used whole-eye transcriptomes to investigate differences in gene expression between tadpole and juvenile southern leopard frogs (Lithobates sphenocephalus), which rely on vision in aquatic and terrestrial light environments, respectively. Because visual physiology changes with light levels, we also tested the effect of light and dark exposure.

Results
We found 42% of genes were differentially expressed in the eyes of tadpoles versus juveniles and 5% for light/dark exposure. Analyses targeting a curated subset of visual genes revealed significant differential expression of genes that control aspects of visual function and development, including spectral sensitivity and lens composition. Finally, microspectrophotometry of photoreceptors confirmed shifts in spectral sensitivity predicted by the expression results, consistent with adaptation to distinct light environments.

Conclusions
Overall, we identified extensive expression-level differences in the eyes of tadpoles and juveniles related to observed morphological and physiological changes through metamorphosis and corresponding adaptive shifts to improve vision in the distinct aquatic and terrestrial light environments these frogs inhabit during their life cycle. More broadly, these results suggest that decoupling of gene expression can mediate the opposing selection pressures experienced by organisms with complex life cycles that inhabit different environmental conditions throughout ontogeny.
Effects and associated transcriptomic landscape changes of methamphetamine on immune cells
Authors: Kong Deshenyue , Mao Jun-Hong , Li Hong , Wang Jian-Yu , Li Yu-Yang , Wu Xiao-Cong , Re Guo-Fen , Luo Hua-You , Kuang Yi-Qun , Wang Kun-Hua 
Published: June 2022

AbstractBackgroundMethamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified.MethodsWe examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape (www.metascape.org).ResultsThe viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process.ConclusionsThe results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells.
HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis
Authors: Talà Adelfia , Guerra Flora , Calcagnile Matteo , Romano Roberta , Resta Silvia Caterina , Paiano Aurora , Chiariello Mario , Pizzolante Graziano , Bucci Cecilia , Alifano Pietro 
Published: June 2022

Abstract
Background
In Neisseria meningitidis the HrpA/HrpB two-partner secretion system (TPS) was implicated in diverse functions including meningococcal competition, biofilm formation, adherence to epithelial cells, intracellular survival and vacuolar escape. These diverse functions could be attributed to distinct domains of secreted HrpA.

Methods
A yeast two-hybrid screening, in vitro pull-down assay and immunofluorescence microscopy experiments were used to investigate the interaction between HrpA and the dynein light-chain, Tctex-type 1 (DYNLT1). In silico modeling was used to analyze HrpA structure. Western blot analysis was used to investigate apoptotic and pyroptotic markers.

Results
The HrpA carboxy-terminal region acts as a manganese-dependent cell lysin, while the results of a yeast two-hybrid screening demonstrated that the HrpA middle region has the ability to bind the dynein light-chain, Tctex-type 1 (DYNLT1). This interaction was confirmed by in vitro pull-down assay and immunofluorescence microscopy experiments showing co-localization of N. meningitidis with DYNLT1 in infected epithelial cells. In silico modeling revealed that the HrpA-M interface interacting with the DYNLT1 has similarity with capsid proteins of neurotropic viruses that interact with the DYNLT1. Indeed, we found that HrpA plays a key role in infection of and meningococcal trafficking within neuronal cells, and is implicated in the modulation of the balance between apoptosis and pyroptosis.

Conclusions
Our findings revealed that N. meningitidis is able to effectively infect and survive in neuronal cells, and that this ability is dependent on HrpA, which establishes a direct protein–protein interaction with DYNLTI in these cells, suggesting that the HrpA interaction with dynein could be fundamental for N. meningitidis spreading inside the neurons. Moreover, we found that the balance between apoptotic and pyroptotic pathways is heavily affected by HrpA.
Single nucleotide polymorphism analysis of pvmdr-1 in Plasmodium vivax isolated from military personnel of Republic of Korea in 2016 and 2017
Authors: Bong Jin-Jong , Lee Wonsig , Lee Chan Hee , Park Quehn , Noh Kyung Tae 
Published: June 2022

Abstract
Background
Malaria chemoprophylaxis using chloroquine (CQ) and primaquine (PQ) has been administered to resident soldiers in the 3rd Army of Republic of Korea (ROK) to prevent malaria infection since the year 1997. Due to mass chemoprophylaxis against malaria, concern exists about the occurrence of chloroquine resistance (CQR). This study aimed to investigate the single nucleotide polymorphisms (SNPs) of the Plasmodium vivax multi-drug resistance protein-1 (pvmdr-1) gene to monitor the risk of CQR.

Methods
SNPs of the pvmdr-1 gene were analysed in 73 soldiers of the 3rd Army of ROK diagnosed with infection by P. vivax.

Results
Quintuple mutations (G698S, L845F, M908L, T958M, and F1076L) were detected in 73 soldiers. A newly identified non-synonymous mutation in the Y541C position had been introduced into P. vivax malaria-endemic areas in ROK, at a frequency of 1.3% (1/73). In addition, synonymous mutations were detected at positions K44 (38.4%, 28/73), L493 (26%, 19/73), T529 (61.6%, 45/73), and E1233 (52.1%, 38/73). Based on these SNPs, pvmdr-1 sequences of ROK were classified into 6 haplotypes. The phylogenetic analysis closed to the type of North Korean showed that P. vivax malaria of ROK could be a reason of influx from North Korea.

Conclusions
This study showed that synonymous and non-synonymous mutations of pvmdr-1 were observed in the malaria chemoprophylaxis-executed regions of ROK from 2016 to 2017. Based on the rapid transition of pvmdr-1 SNPs, continuous surveillance for SNPs of pvmdr-1 related to CQR in the malaria-endemic regions of ROK is essential.
Global prevalence of falls in the older adults: a comprehensive systematic review and meta-analysis
Authors: Salari Nader , Darvishi Niloofar , Ahmadipanah Melika , Shohaimi Shamarina , Mohammadi Masoud 
Published: June 2022

AbstractBackgroundWith increasing life expectancy, declining mortality, and birth rates, the world's geriatric population is increasing. Falls in the older people are one of the most common and serious problems. Injuries from falls can be fatal or non-fatal and physical or psychological, leading to a reduction in the ability to perform activities of daily living. The aim of this study was to determine the prevalence of falls in the older people through systematic review and meta-analysis.MethodsIn this systematic review and meta-analysis, the data from studies on the prevalence of falls in the older people in the world were extracted in the databases of Scopus, Web of Science (WoS), PubMed and Science Direct, and Google Scholar, Magiran and Scientific Information Database (SID) without any time limit until August 2020. To analyze the eligible studies, the stochastic effects model was used, and the heterogeneity of the studies with the I2index was investigated. Data analysis was conducted with Comprehensive Meta-Analysis software (Version 2).ResultsIn the review of 104 studies with a total sample size of 36,740,590, the prevalence of falls in the older people of the world was 26.5% (95% CI 23.4–29.8%). The highest rate of prevalence of falls in the older people was related to Oceania with 34.4% (95% CI 29.2–40%) and America with 27.9% (95% CI 22.4–34.2%). The results of meta-regression indicated a decreasing trend in the prevalence of falls in the older people of the world by increasing the sample size and increasing the research year (P < 0.05).ConclusionThe problem of falls, as a common problem with harmful consequences, needs to be seriously considered by policymakers and health care providers to make appropriate plans for preventive interventions to reduce the rate of falls in the older people.
Co-infections with multiple pathogens in natural populations of Ixodes persulcatus ticks in Mongolia
Authors: Lagunova Ekaterina K. , Liapunova Natalia A. , Tuul Davaakhu , Otgonsuren Gerechuluun , Nomin Davaadorj , Erdenebat Nyamdorj , Abmed Davaajav , Danchinova Galina A. , Sato Kozue , Kawabata Hiroki , Khasnatinov Maxim A. 
Published: June 2022

Abstract
Background
In Mongolia, the taiga tick Ixodes persulcatus is the major vector of tick-borne pathogens. Knowledge about co-infections of these pathogens in ticks is necessary both for understanding their persistence in nature and for diagnosing and treating tick-borne diseases.

Methods
The prevalence of seven tick-borne infections in 346 I. persulcatus collected from the Selenge and Bulgan provinces of Mongolia was evaluated using real-time PCR. Quantification of Borrelia spp. was performed using multiplex quantitative PCR targeting the 16S rRNA gene. Genetic analysis of Borrelia spp. in 11 ticks infected with Borrelia miyamotoi, including six ticks co-infected with Borrelia burgdorferi sensu lato (s.l.), was performed by high-throughput sequencing of the flaB gene fragment.

Results
Six ticks (1.7%) were infected with tick-borne encephalitis virus (TBEV); 171 (49.4%), with B. burgdorferi sensu lato; 17 (4.9%), with B. miyamotoi; 47 (13.6%), with Anaplasma phagocytophilum; and 56 (16.2%), with Ehrlichia sp. Neither Rickettsia sibirica nor R. heilongjiangensis were detected. Borrelia burgdorferi s.l. occurred as co-infection in 55 (32.2%) of all infected ticks. The other pathogens co-infected ticks in 58.8–70.2% of cases. No pairwise associations between co-infecting pathogens were observed, with the exception of a positive association between A. phagocytophilum and Ehrlichia sp. infections. The spirochete loads of B. miyamotoi were significantly higher than those of B. burgdorferi s.l. (mean: 5.2 vs 4.0 log10 genome copies/tick, respectively). Ten isolates of B. miyamotoi belonged to the Siberian lineage. Borrelia burgdorferi s.l was represented by nine isolates of B. afzelii, B. bavariensis and B. garinii.

Conclusions
In populations of I. persulcatus inhabiting the Selenge and Bulgan provinces of Mongolia, five vector-borne pathogens, i.e. TBEV, B. burgdorferi s.l., B. miyamotoi, A. phagocytophilum and Ehrlichia sp., persist independently from each other, with the exception of A. phagocytophilum and Ehrlichia sp. which seem to share the circulation mode. The discrepancies in B. burgdorferi s.l. and B. miyamotoi prevalence and spirochete load per tick suggest that different ecological niches are occupied by Lyme disease and relapsing fever agents. High-throughput sequencing allows genetic identification of borreliae species in co-infected ticks.

Graphical Abstract
Effect of cryotherapy on pain scores and satisfaction levels of patients in cataract surgery under topical anesthesia: a prospective randomized double-blind trial
Authors: Khezri Marzieh Beigom , Akrami Abbas , Majdi Matina , Gahandideh Bijan , mohammadi Navid 
Published: June 2022

Abstract
Objective
To evaluate the effects of cryotherapy on pain scores and satisfaction levels of patients during cataract surgery under topical anesthesia. Eighty patients aged between 55 and 75 years scheduled for cataract surgery were randomly allocated to two study groups to receive topical anesthesia with cryotherapy (TC) or topical anesthesia alone (T) groups. Visual analog pain scores, patient satisfaction level, hemodynamic parameters, and quality of operating conditions were recorded.

Results
Cryotherapy significantly reduced VAS pain scores during surgery (P = 0.014). Although no significant difference in postoperative pain scores, opioid consumption, heart rate, and mean arterial blood pressure was seen in the postoperative period. The surgeon reported better quality of operating conditions in the TC group (P = 0.018). Cryotherapy as a complementary method with topical anesthesia reduced pain scores of patients during surgery. It also produced a better quality of operating conditions for surgeons. There was no significant difference in either postoperative pain scores or opioid consumption.
Trial registration This trial was registered at Iranian clinical trial registering: IRCT registration number: IRCT2017052734091N2
Endoplasmic reticulum stress modulates the fate of lung resident mesenchymal stem cell to myofibroblast via C/EBP homologous protein during pulmonary fibrosis
Authors: Yang Xiaoyu , Sun Wei , Jing Xiaoyan , Zhang Qian , Huang Hui , Xu Zuojun 
Published: June 2022

Abstract
Background
As a fatal interstitial lung disease, idiopathic pulmonary fibrosis (IPF) was characterized by the insidious proliferation of extracellular matrix (ECM)-producing mesenchymal cells. Recent studies have demonstrated that lung resident mesenchymal/stromal cells (LR-MSC) are the source of myofibroblasts. Endoplasmic reticulum (ER) stress is prominent in IPF lung. This study sought to investigate the effects of ER stress on the behavior of LR-MSC during pulmonary fibrosis.

Methods
ER stress and myofibroblast differentiation of LR-MSC in patients with IPF were evaluated. Primary mouse LR-MSC was harvested and used in vitro for testing the effects of ER stress and C/EBP homologous protein (CHOP) on LR-MSC. Adoptive transplantation of LR-MSC to bleomycin-induced pulmonary fibrosis was done to test the in vivo behavior of LR-MSC and its influence on pulmonary fibrosis.

Results
We found that myofibroblast differentiation of LR-MSC is associated with ER stress in IPF and bleomycin-induced mouse fibrotic lung. Tunicamycin-induced ER stress impairs the paracrine, migration, and reparative function of mouse LR-MSC to injured type 2 alveolar epithelial cells MLE-12. Overexpression of the ER stress responder C/EBP homologous protein (CHOP) facilitates the TGFβ1-induced myofibroblast transformation of LR-MSC via boosting the TGFβ/SMAD signaling pathway. CHOP knockdown facilitates engraftment and inhibits the myofibroblast transformation of LR-MSC during bleomycin-induced pulmonary fibrosis, thus promoting the efficacy of adopted LR-MSC in alleviating pulmonary fibrosis.

Conclusion
Our work revealed a novel role that ER stress involved in pulmonary fibrosis by influencing the fate of LR-MSC and transformed to “crime factor” myofibroblast, during which CHOP acts as the key modulator. These results indicate that pharmacies targeting CHOP or therapies based on CHOP knockdown LR-MSC may be promising ways to treat pulmonary fibrosis.
Piperine increases striatal levels of DA and TH and decreases α-syn and Aβ42 deposition in PDD mice by regulting autophagy: downexpression Beclin-1 and LC3B and upexpression p62
Authors: Huang Liping , Zhong Xiaoqin , Zhou Zhongliu , Cai Yuanliang , Deng Minzhen 
Published: June 2022

AbstractPiperine, the major pharmacological ingredient of pepper, can delay the procession of neuropharmacological effects, but its effects and mechanisms on Parkinson's disease dementia (PDD) mice is still unclear, we investigated whether piperine could help treating PDD mice. Here, PDD mice were randomly divided into eight groups (n = 12/group): a normal control group, a PDD model group, a madopar group, an autophagy inhibitor group, an autophagy activator group, and groups receiving low, medium or high doses of piperine respectively. The normal control and PDD model mice were injected with saline. Treatments were administered to the mice once per day continuously for 30 days. The behavioral tests were assessed. Dopamine (DA), Monoamine Oxidase-B (MAO-B), DOPA decarboxylase (DDC), β-secretase, acetylcholinesterase (AChE), amyloid β42 (Aβ42), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected. α-synuclein (α-syn), tyrosine hydroxylase (TH), HSP90, Beclin-1, LC3B, p62 mRNA levels and miRNA-99a-5p expression were determined. Neuronal histology was observed. The behavior of PDD mice improved significantly after peperine treatment compared with the PDD model mice. In addition, our results also showed that peperine treatment increased DA, TH, DDC and p62 levels, decreased MAOB, β-secretase, AChE, Aβ42, TNF-α, IL-6, Beclin-1 and LC3B levels, and down-regulated α-syn, HSP90, Beclin-1, LC3B mRNA levels and miR-99a-5p expression. These findings suggest that piperine may reduce the expression of mmu-miR-99a-5p and autophagy-related factors (HSP90, Beclin-1, LC3B and p62) to alleviate the neurological impairment of PDD mice, which is shown to slow down the process of DA metabolism and Aβ production and resist neuroinflammation.
Comparison of surface roughness of root cementum and orthodontically induced root resorption craters from high- and low-fluoridation areas: a 3D confocal microscopy study
Authors: Mann Chelsea , Cheng Lam L. , Ranjitkar Sarbin , Elekdag-Turk Selma T. , Turk Tamer , Darendeliler M. Ali 
Published: June 2022

Abstract
Background
Fluoride has a major role in strengthening the structure of enamel against acids. Despite differences between caries and root resorption processes, both events inherently involve acidic dissolution of dental tissues. The aim of the present study was to investigate the effects of water fluoridation levels on the surface roughness of root cementum and resorption craters. The findings provided more insight into the influence of fluoride on the surfaces of intact cementum surface and resorption craters.

Methods
Twenty-eight orthodontic patients were recruited from two cities in Turkey, with high (≥ 2 ppm) and low (≤ 0.05 ppm) water fluoridation. These patients needed bilateral maxillary first premolar extraction as part of their orthodontic treatment and were allocated into two study groups (n = 14 in each group) based on water fluoridation exposure level: the high-fluoride group (HF) and low-fluoride group (LF). 150 g of buccal tipping forces was applied to all maxillary first premolar teeth for 12 weeks with a beta-titanium spring which was reactivated every 4 weeks. All maxillary premolars were removed at the end of the experiment for surface roughness assessment using three-dimensional confocal microscopy and the associated software. The buccal root surface and the largest buccal resorption crater were investigated.

Results
Resorption craters were significantly rougher in LF group compared to HF group (p = 0.002). Craters were rougher than the intact root surfaces (p = 0.000). Cervical and apical regions were significantly rougher than the middle region (p = 0.000 and p = 0.024, respectively).

Conclusions
Higher water fluoridation level of ≥ 2 ppm resulted in significantly smoother root resorption craters than low water fluoridation level of ≤ 0.05 ppm when the teeth were subjected to 150 g of buccal tipping force. Fluoride seems to have a protective role at the interface of root resorption, and further mineral or histological studies may shed light on the exact protective process against root resorption.