bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stressed Out About Plasmodium falciparum Gametocytogenesis
Authors: Usui Miho , Williamson Kim C. 
Published: December 2021

Blocking malaria transmission is critical to malaria control programs but remains a major challenge especially in endemic regions with high levels of asymptomatic infections. New strategies targeting the transmissible sexual stages of the parasite, called gametocytes, are needed. This review focuses on P. falciparum gametocytogenesisin vivoandin vitro. Highlighting advances made elucidating genes required for gametocyte production and identifying key questions that remain unanswered such as the factors and regulatory mechanisms that contribute to gametocyte induction, and the mechanism of sequestration. Tools available to begin to address these issues are also described to facilitate advances in our understanding of this important stage of the life cycle.
Moving From Indifference to Responsibility: Reframing Environmental Behavior Among College Students in Israel
Authors: Dopelt Keren , Loren Ori , Gapich Gal , Davidovitch Nadav 
Published: December 2021

Objectives: To examine the level of knowledge, attitudes, and behavior of students on topics related to climate change and the relationship between those variables.Methods: A cross-sectional study using an online questionnaire, including 704 students. Statistical analysis was performed using Pearson correlations, t-tests, one-way ANOVA, and regression models.Results: Only 42% of participants understood what climate change meant, and 14% indicated their indifference toward it. Students had a moderate level of knowledge about the impact of climate change, and their attitudes were moderately positive, yet they demonstrated poor environmental behavior. We found positive relationships between variables, with attitudes mediating the relationship between knowledge and behavior. Women demonstrated more pro-environmental behavior than men.Conclusions: Our results highlight the importance of raising awareness of climate change's effects and its mitigation. Pro-environmental behavior requires long-term thinking and priorities for the future rather than benefits in the present. Future environmental education campaigns should emphasize individual contributions to environmental impacts in the context of climate change, as well as environmentally relevant consumption habits. We suggest including an introductory reflective and emancipatory course in environmental studies in all departments, emphasizing public health aspects.
Epigenetic and Immune-Cell Infiltration Changes in the Tumor Microenvironment in Hepatocellular Carcinoma
Authors: Wu Zeng-Hong , Yang Dong-Liang , Wang Liang , Liu Jia 
Published: December 2021

BackgroundEpigenetics regulate gene expression without altering the DNA sequence. Epigenetics targeted chemotherapeutic approach can be used to overcome treatment resistance and low response rate in HCC. However, a comprehensive review of genomic data was carried out to determine the role of epigenesis in the tumor microenvironment (TME), immune cell-infiltration characteristics in HCC is still insufficient.MethodsThe association between epigenetic-related genes (ERGs), inflammatory response-related genes (IRRGs) and CRISPR genes was determined by merging genomic and CRISPR data. Further, characteristics of immune-cell infiltration in the tumor microenvironment was evaluated.ResultsNine differentially expressed genes (ANP32B, ASF1A, BCORL1, BMI1, BUB1, CBX2, CBX3, CDK1, and CDK5) were shown to be independent prognostic factors based on lasso regression in the TCGA-LIHC and ICGC databases. In addition, the results showed significant differences in expression of PDCD-1 (PD-1) and CTLA4 between the high- and low-epigenetic score groups. The CTRP and PRISM-derived drug response data yielded four CTRP-derived compounds (SB-743921, GSK461364, gemcitabine, and paclitaxel) and two PRISM-derived compounds (dolastatin-10 and LY2606368). Patients with high ERGs benefited more from immune checkpoint inhibitor (ICI) therapy than patients with low ERGs. In addition, the high ERGs subgroup had a higher T cell exclusion score, while the low ERGs subgroup had a higher T cell dysfunction. However, there was no difference in microsatellite instability (MSI) score among the two subgroups. Further, genome-wide CRISPR-based loss-of function screening derived from DepMap was conducted to determine key genes leading to HCC development and progression. In total, 640 genes were identified to be essential for survival in HCC cell lines. The protein-protein interaction (PPI) network demonstrated that IRRGs PSEN1 was linked to most ERGs and CRISPR genes such as CDK1, TOP2A, CBX2 and CBX3.ConclusionEpigenetic alterations of cancer-related genes in the tumor microenvironment play a major role in carcinogenesis. This study showed that epigenetic-related novel biomarkers could be useful in predicting prognosis, clinical diagnosis, and management in HCC.
Clinical Outcomes of Patients With Primary Membranous Nephropathy and Subnephrotic Proteinuria
Authors: He Peng , Zha Yang , Liu Jing , Wang Hanmin , He Lijie 
Published: December 2021

Objectives: To update the information about the prognosis of patients with primary membranous nephropathy (MN) and subnephrotic proteinuria and identify the relevant predictors.Methods: In total, 474 cases of biopsy-proven primary MN with at least 18 months of follow-up were reviewed to determine the outcomes of the subgroup of patients that presented with subnephrotic proteinuria. Clinical data included initial proteinuria and microhematuria, defined as the average proteinuria/microhematuria of the first 6 months during the course. Outcomes included partial remission (PR), complete remission (CR), nephrotic proteinuria progression, and kidney function progression, defined as ≥50% loss of kidney function or end-stage kidney disease.Results: In total, 205 patients with primary MN and subnephrotic proteinuria at biopsy were eligible. During a median follow-up of 43 months, 200 (97.56%), 167 (81.46%), and 53 (25.85%) patients attained PR, CR, and nephrotic proteinuria progression, respectively. Only one patient (0.49%) progressed to the kidney function progression. By multivariate Cox hazards regression analyses, the initial proteinuria was identified as the independent predictor for PR, CR, and nephrotic proteinuria progression with adjusted hazard ratios (aHRs) of 0.67 (95% confidence interval, 0.56–0.80), 0.50 (95% CI, 0.40–0.63), and 2.97 (95% CI, 2.23–3.97), respectively. A higher level of initial microhematuria was also associated with an increased risk of nephrotic proteinuria progression. The corresponding aHR was 1.11 (95% CI, 1.05–1.17).Conclusion: Among patients with primary MN and subnephrotic proteinuria, although the overall prognosis is excellent, dynamic detection and effective management of proteinuria remain important. In addition, initial microhematuria may be another predictor of nephrotic proteinuria progression.
Repetitive Transcranial Magnetic Stimulation for Alzheimer’s Disease Based on Apolipoprotein E Genotyping: Protocol for a Randomized Controlled Study
Authors: Wei Naili , Chen Jian 
Published: December 2021

To date, there is a shortage of effective treatment strategies for Alzheimer’s disease (AD), and although repetitive transcranial magnetic stimulation (rTMS) can improve AD cognitive function, there are obvious individual differences, which may be related to different apolipoprotein E (APOE) genotypes. As the risk and pathogenesis of AD varies greatly among different genotypes precise treatment strategies should be implemented depending upon genotype, which has not been proved by clinical studies. Apart from that, the published clinical studies are highly heterogeneous, and therefore, systematic and well-developed randomized controlled Trails (RCT) and demonstration of precise administration protocols are required. To verify this hypothesis, this project designed a RCT study, and randomly divided apoE4 carrier AD and non-carrier AD into high-frequency rTMS (HF-rTMS) or low-frequency rTMS (LF-rTMS) treatment groups. Specifically, 80 patients with AD, namely 48 APOE4 carriers and 32 non-APOE4 carriers will be included in the study. After that, based on different stimulation frequencies of rTMS, they will be divided into the HF-rTMS group and the LF-rTMS group, when patients with AD will be randomly assigned to different treatment groups. After AD patients are involved in the study, their memory, cognition, anxiety, depression and activities of daily living will be tested before and during 2 weeks of rTMS. Furthermore, peripheral blood will be collected before and after treatment to detect changes in pathological indexes via MSD platform (Meso Scale Discovery), while 32-channel EEG data will be also collected to detect and analyze changes in gamma oscillation. In addition, these patients will be followed up for 6 months and their neuropsychological scale was also evaluated every month. At present, our study has included 18 AD patients (10 APOE4 carriers; 8 non-carriers). Our study is still in progress. The grouping has not been unblinded. But the preliminary data demonstrated that non-carriers had better MoCA score improvement than APOE4 carriers. The results indicated that the two populations of AD patients should be treated differently. Thus, this project will provide direction for precision rTMS in AD and also promotes a shift in relevant treatment philosophy.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100041625].
Dual-Task Performance in Hearing-Impaired Older Adults—Study Protocol for a Cross-Sectional Mobile Brain/Body Imaging Study
Authors: Wunderlich Anna , Vogel Oliver , Šömen Maja Maša , Peskar Manca , Fricke Madeleine , Gramann Klaus , Protzak Janna , Marusic Uros , Wollesen Bettina 
Published: December 2021

Background: Hearing impairments are associated with reduced walking performance under Dual-task (DT) conditions. Little is known about the neural representation of DT performance while walking in this target group compared to healthy controls or younger adults. Therefore, utilizing the Mobile Brain/Body Imaging approach (MoBI), we aim at gaining deeper insights into the brain dynamics underlying the interaction of cognitive and motor processes during different DT conditions (visual and auditory) controlling for age and the potential performance decrements of older adults with hearing impairments.Methods: The cross-sectional study integrates a multifactorial mixed-measure design. Between-subject factors grouping the sample will be age (younger vs. older adults) and hearing impairment (mild vs. not hearing impaired). The within-subject factors will be the task complexity (single- vs. DT) and cognitive task modality (visual vs. auditory). Stimuli of the cognitive task will vary according to the stimulus modality (visual vs. auditory), presentation side (left vs. right), and presentation-response compatibility (ipsilateral vs. contralateral). Analyses of DT costs and underlying neuronal correlates focus either on gait or cognitive performance. Based on an a priori sample size calculation 96 (48 healthy and 48 mildly hearing impaired) community-dwelling older adults (50–70 years) and 48 younger adults (20–30 years) will be recruited. Gait parameters of speed and rhythm will be captured. EEG activity will be recorded using 64 active electrodes.Discussion: The study evaluates cognitive-motor interference (CMI) in groups of young and older adults as well as older adults with hearing impairment. The underlying processes of the interaction between motor and cognitive tasks will be identified at a behavioral and neurophysiological level comparing an auditory or a visual secondary task. We assume that performance differences are linked to different cognitive-motor processes, i.e., stimulus input, resource allocation, and movement execution. Moreover, for the different DT conditions (auditory vs. visual) we assume performance decrements within the auditory condition, especially for older, hearing-impaired adults. Findings will provide evidence of general mechanisms of CMI (ST vs. DT walking) as well as task-specific effects in dual-task performance while over ground walking.
Long-Term Weight Change and Glycemic Control in Patients With Type 2 Diabetes Mellitus and Treated vs. Untreated Sleep-Disordered Breathing—Analysis From the DIAbetes COhoRtE
Authors: Schaller Louisa , Arzt Michael , Jung Bettina , Böger Carsten A. , Heid Iris M. , Stadler Stefan 
Published: December 2021

Hypothesis: Positive airway pressure (PAP) is the standard treatment for sleep-disordered breathing (SDB), a prevalent condition in patients with type 2 diabetes mellitus (DM2). Recent studies showed that short-term PAP treatment may cause weight gain. However, long-term data for patients with DM2 are scarce. Therefore, the aim of the present analysis was to assess changes in weight and glycemic control in patients with DM2 and treated vs. untreated SDB.Methods: The DIAbetes COhoRtE (DIACORE) study is a prospective population-based cohort study in patients with DM2. At baseline, patients of the DIACORE-SDB sub-study were tested for SDB [defined as apnea-hypopnea-index (AHI) ≥ 15/h] using a two-channel ambulatory SDB-monitoring device. In this observational study, PAP treatment was initiated in a subgroup of patients with SDB (SDB PAP) within clinical routine between the baseline and first follow-up visit [median observation period of 2.3 (2.2; 2.4) years], whereas the other patients with SDB did not receive PAP (SDB untreated). At baseline and first follow-up visit, weight and HbA1c were assessed.Results: Of the 346 patients with SDB [mean age 68 years, 71% male, body-mass index (BMI) 31.9 kg/m2], 17% were in the SDB PAP and 83% in the SDB untreated group. Weight change within the observation period was similar in both groups (−0.2 and −0.9 kg; p = 0.322). The percentage of patients with severe weight gain (≥ 5 kg) within the observation period was significantly higher in the SDB PAP group compared to the SDB untreated group (15.0 vs. 5.6%; p = 0.011). Multivariable regression analysis, accounting for baseline HbA1c, insulin substitution, BMI, waist-to-hip ratio (WHR), physical activity, and AHI, showed that PAP treatment was significantly associated with a weight gain ≥ 5 kg [odds ratio (OR) = 3.497; 95% CI (1.343; 9.106); p = 0.010] and an increase in HbA1c [B = 2.410; 95% CI (0.118; 4.702); p = 0.039].Conclusion: Median weight change was similar in patients with SDB with and without PAP treatment. However, patients with DM2 and PAP treatment have an increased risk of severe long-term weight gain and an increase in HbA1c.Clinical Trial registration: DRKS00010498
Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders
Authors: Fan Yangyi , Xu Yicheng , Shen Ming , Guo Huailian , Zhang Zhaoxu 
Published: December 2021

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P &lt; 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.
Reduced Risk of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From a United States Claims Database
Authors: Wu Chengyuan , Nagel Sean J. , Agarwal Rahul , Pötter-Nerger Monika , Hamel Wolfgang , Sharan Ashwini D. , Connolly Allison T. , Cheeran Binith , Larson Paul S. 
Published: December 2021

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States.Design: Retrospective, contemporaneous cohort study.Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018.Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, of which 3,869 patients had a de novo implant and primary diagnosis of PD or ET. Follow-up of 3 months was available for 3,810 patients, 12 months for 3,561 patients, and 24 months for 1,812 patients.Intervention: Implantation of a modern directional (MD) or traditional omnidirectional (TO) DBS system.Primary and Secondary Outcome Measures: We hypothesized that MD systems would impact complication rates. Reoperation rate was the primary outcome. Associated diagnoses, patient characteristics, and implanting center details served as covariates. Kaplan–Meier analysis was performed to compare rates of event-free survival and regression models were used to determine covariate influences.Results: Patients implanted with modern systems were 36% less likely to require reoperation, largely due to differences in acute reoperations and intracranial lead reoperations. Risk reduction persisted while accounting for practice differences and implanting center experience. Risk reduction was more pronounced in patients with PD.Conclusions: In the first multicenter analysis of device-related complications including modern DBS systems, we found that modern systems are associated with lower reoperation rates. This risk profile should be carefully considered during device selection for patients undergoing DBS for PD or ET. Prospective studies are needed to further investigate underlying causes.
Anlotinib Combined With Anti-PD-1 Antibodies Therapy in Patients With Advanced Refractory Solid Tumors: A Single-Center, Observational, Prospective Study
Authors: Yuan Min , Zhu Zhongzheng , Mao Wei , Wang Hui , Qian Hong , Wu Jianguo , Guo Xianling , Xu Qing 
Published: December 2021

IntroductionAnlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and suppressing tumor growth. Modulation of tumor suppressive immune microenvironment via the inhibition of vascular endothelial growth factor may augment the activity of immune checkpoint inhibitors. Here we described the results of safety, and clinical efficacy of anlotinib combined with immunotherapy in patients with advanced solid tumors, the serum cytokine levels, and peripheral blood T lymphocyte populations were detected simultaneously.MethodsTwenty six cases with advanced late-stage cancers including lung, gallbladder, endometrial, gastric, pancreatic, penile cancers and melanoma were treated since January 2019. Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 (21 days as a course) plus anti-PD-1 antibodies every 3 weeks until progression or intolerable toxicity. Imaging was performed every 6 weeks for the first year of therapy. Blood samples were collected from patients prospectively. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and circulating immune cell subsets were measured at baseline and after two cycles of treatment via flow cytometry.ResultsThere were ten tumor types enrolled with lung, gallbladder, cholangiocarcinoma and soft tissue sarcoma being the most common. Most patients had received front line treatments for metastatic disease (80.8%). The objective response rate (ORR) was 23.1%, including one complete response (CR) (3.8%) and five partial responses (PR) (19.2%) and a disease control rate (DCR=CR+PR+SD) of 80.8% (21 of 26). The median PFS was 4.77 months (95% CI: 4.10-5.44 months). Three patients (11.5%) had grade 3 treatment-related adverse events. There were no grade 4 or 5 treatment-related adverse events. Grades 3 toxicities included hand-foot syndrome (n=2) and hypertension (n=1). Higher serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and lower ratios of CD4/CD8 T cells were found in the responders compared with non-responders.ConclusionsThe preliminary data showed that the combination of anlotinib and anti-PD-1 antibodies demonstrated promising durable antitumor efficacy with acceptable toxicity in patients with various advance tumors, and promoted favorable changes in serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and circulating immune cell subsets in clinical responders. It is worth to further validate the efficacy in a randomized prospective trial.