Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling.

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

OBJECTIVE: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). METHODS: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. RESULTS: Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. SIGNIFICANCE: This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. PLAIN LANGUAGE SUMMARY: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Alterations in brain network functional connectivity and topological properties in DRE patients.

Objective: The study aimed to find the difference in functional network topology on interictal electroencephalographic (EEG) between patients with drug-resistant epilepsy (DRE) and healthy people. Methods: We retrospectively analyzed the medical records as well as EEG data of ten patients with DRE and recruited five sex-age-matched healthy controls (HC group). Each participant remained awake while undergoing video-electroencephalography (vEEG) monitoring. After excluding data that contained abnormal discharges, we screened EEG segments that were free of artifacts and put them together into 20-min segments. The screened data was bandpass filtered to different frequency bands (delta, theta, alpha, beta, and gamma). The weighted phase lag index (wPLI) and the network properties were calculated to evaluate changes in the topology of the functional network. Finally, the results were statistically analyzed, and the false discovery rate (FDR) was used to correct for differences after multiple comparisons. Results: In the full frequency band (0.5-45 Hz), the functional connectivity in the DRE group during the interictal period was significantly lower than that in the HC group (p < 0.05). Compared to the HC group, in the full frequency band, the DRE group exhibited significantly decreased clustering coefficient (CC), node degree (D), and global efficiency (GE), while the characteristic path length (CPL) significantly increased (p < 0.05). In the sub-frequency bands, the functional connectivity of the DRE group was significantly lower than that of the HC group in the delta band but higher in the alpha, beta, and gamma bands (p < 0.05). The statistical results of network properties revealed that in the delta band, the DRE group had significantly decreased values for D, CC, and GE, but in the alpha, beta, and gamma bands, these values were significantly increased (p < 0.05). Additionally, the CPL of the DRE group significantly increased in the delta and theta bands but significantly decreased in the alpha, beta, and gamma bands (p < 0.05). Conclusion: The topology structure of the functional network in DRE patients was significantly changed compared with healthy people, which was reflected in different frequency bands. It provided a theoretical basis for understanding the pathological network alterations of DRE.

Substance use, psychiatric symptoms, personal mastery, and social support among COVID-19 long haulers: A compensatory model

BackgroundSubstance use has become a critical health concern during the COVID-19 pandemic, and emerging attention has been paid to people with the persistent symptoms of COVID-19 (COVID-19 long haulers) due to their high vulnerability. However, scant research has investigated their substance use and relevant psychosocial factors. The current study was to (1) examine substance use behaviors (i.e., legal drug use, illicit drug use, and non-medical use of prescription drugs); and (2) assessed their associations with psychiatric symptoms (i.e., depression, anxiety, and post-traumatic stress disorder) and psychosocial factors (i.e., personal mastery and social support) among COVID-19 long haulers. MethodsIn January - March 2022, 460 COVID-19 long haulers (50% female), with an average age of 32, completed online surveys regarding their demographics, substance use, psychiatric symptoms, and psychosocial factors. ResultsIn the past three months, the most commonly used or non-medically used substances were tobacco (82%) for legal drugs, cocaine (53%) for illicit drugs, and prescription opioids (67%) for prescription drugs. Structural equation modeling suggested that psychiatric symptoms were positively associated with substance use behaviors ({beta}s = .38 to .68, ps < .001), while psychosocial factors were negatively associated with substance use behaviors ({beta}s = -.61 to -.43, ps < .001). ConclusionSubstance use is common in COVID-19 long haulers and psychiatric symptoms are the risk factors. Personal mastery and social support appear to offer protection offsetting the psychiatric influences. Substance use prevention and mental health services for COVID-19 long haulers should attend to personal mastery and social support.

Revealing geographic transmission pattern of COVID-19 using neighborhood-level simulation with human mobility data and SEIR model: A Case Study of South Carolina

Direct human physical contact accelerates COVID-19 transmission. Smartphone mobility data has been an emerging data source to reveal fine-grained human mobility, which can be used to estimate the intensity of physical contact surrounding different locations. Our study applied smartphone mobility data to simulate the second wave spreading of COVID-19 in January 2021 in three major metropolitan statistical areas (Columbia, Greenville, and Charleston) in South Carolina, United States. Based on the simulation, the number of historical county-level COVID-19 cases was allocated to neighborhoods (Census blockgroups) and points of interest (POIs), and the transmission rate of each allocated place was estimated. The result reveals that the COVID-19 infections during the study period mainly occurred in neighborhoods (86%), and the number is approximately proportional to the neighborhoods population. Restaurants and elementary and secondary schools contributed more COVID-19 infections than other POI categories. The simulation results for the coastal tourism Charleston area show high transmission rates in POIs related to travel and leisure activities. The results suggest that the neighborhood-level infectious controlling measures are critical in reducing COVID-19 infections. We also found that the households of lower socioeconomic status may be an umbrella against infection due to fewer visits to places such as malls and restaurants associated with their low financial status. Control measures should be tailored to different geographic locations since transmission rates and infection counts of POI categories vary among metropolitan areas.

Dynamic Changes of Brain Activity in Patients With Disorders of Consciousness During Recovery of Consciousness.

The disorder of brain activity dynamics is one of the main characteristics leading to disorders of consciousness (DOC). However, few studies have explored whether the dynamics of brain activity can be modulated, and whether the dynamics of brain activity can help to evaluate the state of consciousness and the recovery progress of consciousness. In current study, 20 patients with minimally conscious state (MCS) and 13 patients with vegetative state (VS) were enrolled, and resting state electroencephalogram (EEG) data and the coma recovery scale-revised (CRS-R) scores were collected three times before and after high-definition transcranial direct current stimulation (HD-tDCS) treatment. The patients were divided into the improved group and the unimproved group according to whether the CRS-R scores were improved after the treatment, and the dynamic changes of resting state EEG microstate parameters during treatment were analyzed. The results showed the occurrence per second (OPS) of microstate D was significantly different between the MCS group and VS group, and it was positively correlated with the CRS-R before the treatment. After 2 weeks of the treatment, the OPS of microstate D improved significantly in the improved group. Meanwhile, the mean microstate duration (MMD), ratio of time coverage (Cov) of microstate C and the Cov of microstate D were significantly changed after the treatment. Compared with the microstates parameters before the treatment, the dynamic changes of parameters with significant difference in the improved group showed a consistent trend after the treatment. In contrast, the microstates parameters did not change significantly after the treatment in the unimproved group. The results suggest that the dynamics of EEG brain activity can be modulated by HD-tDCS, and the improvement in brain activity dynamics is closely related to the recovery of DOC, which is helpful to evaluate the level of DOC and the progress of recovery of consciousness.

Does place connectivity moderate the association between concentrated disadvantage and COVID-19 fatality in the United States?

Concentrated disadvantaged areas have been disproportionately affected by COVID-19 outbreak in the United States (US). Meanwhile, highly connected areas may contribute to higher human movement, leading to higher COVID-19 cases and deaths. This study examined whether place connectivity moderated the association between concentrated disadvantage and COVID-19 fatality. Using COVID-19 fatality over four time periods, we performed mixed-effect negative binomial regressions to examine the association between concentrated disadvantage, Twitter-based place connectivity, and county-level COVID-19 fatality, considering potential state-level variations. Results revealed that concentrated disadvantage was significantly associated with an increased COVID-19 fatality. More importantly, moderation analysis suggested that place connectivity significantly exacerbated the harmful effect of concentrated disadvantage on COVID-19 fatality, and this significant moderation effect increased over time. In response to COVID-19 and other future infectious disease outbreaks, policymakers are encouraged to focus on the disadvantaged areas that are highly connected to provide additional pharmacological and non-pharmacological intervention policies.

Social capital, urbanization level, and COVID-19 vaccination uptake in the United States: A national level analysis

Vaccination remains the most promising mitigation strategy for the COVID-19 pandemic. However, existing literature shows significant disparities in vaccination uptake in the United States. Using publicly available national-level data, we aimed to explore if county-level social capital can further explain disparities in vaccination uptake rate adjusting for demographic and social determinants of health (SDOH) variables; and if association between social capital and vaccination uptake may vary by urbanization level. Bivariate analyses and hierarchical multivariable quasi-binomial regression analysis were conducted, then the regression analysis was stratified by urban-rural status. The current study suggests that social capital contributes significantly to the disparities of vaccination uptake in the US. The results of stratification analysis show common predictors of vaccine uptake but also suggest various patterns based on urbanization level regarding the associations of COVID-19 vaccination uptake with SDOH and social capital factors. The study provides a new perspective to address disparities in vaccination uptake through fostering social capital within communities, which may inform tailored public health intervention efforts in enhancing social capital and promoting vaccination uptake.

Where the truth really lies: Listening to voices from African American communities in the Southern States about COVID-19 vaccine information and communication

BackgroundHigh uptake of COVID-19 vaccine is one of the most promising measures to control the pandemic. However, some African American (AA) communities exhibit vaccination hesitancy due to mis-or dis-information. It is important to understand the challenges in accessing reliable COVID-19 vaccine information and to develop feasible health communication interventions based on voices from AA communities. MethodsWe conducted two focus group discussions (FGDs) among 18 community leaders recruited from three counties in South Carolina on October 8 and October 29, 2021. The FGDs were conducted online via Zoom meetings. The FGD data were managed and thematically analyzed using QSR NVivo 12 software. ResultsParticipants (73% female and 61% between the ages of 18 and 30) worked primarily in colleges (55.5%), churches (39%), and health agencies (5.5%). We found that challenges of accessing reliable COVID-19 vaccine information in AA communities primarily included structural barriers, information barriers, and lack of trust. Community leaders recommended recruiting trusted messengers, using homecoming events, football games, and other social events to reach target populations and conducting health communication campaigns through open dialogue among stakeholders. ConclusionHealth communication interventions on COVID-19 vaccine uptake should be grounded in ongoing community engagement, trust-building activities, and transparent communication about vaccine development. Tailoring health communication interventions to different groups may help reduce misinformation spread and thus promote vaccination in AA communities in the Southern States.

Impact of COVID-19 symptoms on social aspects of life of female long haulers: A qualitative study

IntroductionPersistent COVID-19 symptoms (long COVID) may bring numerous challenges to long haulers social lives. Women may have to endure more profound impacts given their social roles and existing structural inequality. This study aims to explore the impacts of long COVID on various aspects of social life among female long haulers. MethodsWe conducted 15 semi-structured interviews with female long haulers in the United States purposely recruited from Facebook groups, Slack groups, and organization websites. The interviews were audio recorded after appropriate consent and transcribed verbatim. Inductive approach was applied in thematic analysis, which consists of six stages: becoming familiar with data, developing initial codes, extracting themes, refining themes, labeling themes, and reporting. The MAXQDA software was used in data analysis. ResultsPersistent COVID-19 symptoms negatively affected female long haulers social lives in many aspects including physical function, financial security, social relationship, conflict of social roles, and social stigma. Physical limitations changed their body image. Social isolation and work-family conflicts caused huge stress. They experienced internalization of stigma and job insecurities. Shifting to new methods of communication, especially social media may buffer the negative effects of social isolation because of long COVID. ConclusionExisting policies and intervention programs need to be adapted to address the challenges and barriers that long haulers face in returning to normal social life, especially for females. Tailored social life-related recommendations and social support are needed for female long haulers.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Resibufogenin suppresses human hepatocellular carcinoma cell proliferation, migration and invasion in vitro / 药学学报

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

How different pre-existing mental disorders and their co-occurrence affects clinical outcomes of COVID-19? A study based on real-world data in the Southern United States

ImportanceA growing body of research focuses on the impact of pre-existing mental disorders on clinical outcomes of COVID-19 illness. Although a psychiatric history might be an independent risk factor for COVID-19 infection and mortality, no studies have systematically investigated how different clusters of pre-existing mental disorders may affect COVID-19 clinical outcomes or showed how the coexistence of mental disorder clusters is related to COVID-19 clinical outcomes. ObjectiveTo explore how different pre-existing mental disorders and their co-occurrence affects COVID-19-related clinical outcomes based on real-world data. Design, Setting, and ParticipantsUsing a retrospective cohort study design, a total of 476,775 adult patients with lab-confirmed and probable COVID-19 between March 06, 2020 and April 14, 2021 in South Carolina, United States were included in the current study. The electronic health record data of COVID-19 patients were linked to all payer-based claims data through the SC Revenue and Fiscal Affairs Office. Main Outcomes and MeasuresKey COVID-19 clinical outcomes included severity, hospitalization, and death. COVID-19 severity was defined as asymptomatic, mild, and moderate/severe. Pre-existing mental disorder diagnoses from Jan 2, 2019 to Jan 14, 2021 were extracted from the patients healthcare utilization data via ICD-10 codes. Mental disorders were categorized into internalizing disorders, externalizing disorders, and thought disorders. ResultsOf the 476,775 COVID-19 patients, 55,300 had pre-existing mental disorders. There is an elevated risk of COVID-19-related hospitalization and death among participants with pre-existing mental disorders adjusting for key socio-demographic covariates (i.e., age, gender, race, ethnicity, residence, smoking). Co-occurrence of any two clusters was positively associated with COVID-19-related hospitalization and death. The odds ratio of being hospitalized was 2.50 (95%CI 2.284, 2.728) for patients with internalizing and externalizing disorders, 3.34 (95%CI 2.637, 4.228) for internalizing and thought disorders, 3.29 (95%CI 2.288, 4.733) for externalizing and thought disorders, and 3.35 (95%CI 2.604, 4.310) for three clusters of mental disorders. Conclusions and RelevancePre-existing internalizing disorders, externalizing disorders, and thought disorders are positively related to COVID-19 hospitalization and death. Co-occurrence of any two clusters of mental disorders have elevated risk of COVID-19-related hospitalization and death compared to those with a single cluster.

Temporal Geospatial Analysis of COVID-19 Pre-infection Determinants of Risk in South Carolina

IntroductionDisparities and their geospatial patterns exist in coronavirus disease 2019 (COVID-19) morbidity and mortality for people who are engaged with clinical care. However, studies centered on viral infection cases are scarce. It remains unclear with respect to the disparity structure, its geospatial characteristics, and the pre-infection determinants of risk (PIDRs) for people with the infection. This work aimed to assess the geospatial associations between PIDRs and COVID-19 infection at the county level in South Carolina by different timepoints during the pandemic. MethodWe used global models including spatial error model (SEM), spatial lag model (SLM), and conditional autoregressive model (CAR), as well as geographically weighted regression model (GWR) as a local model to examine the associations between COVID-19 infection rate and PIDRs. The data were retrieved from multiple sources including USAFacts, US Census Bureau, and Population Estimates Program. ResultsThe percentage of males and the percentage of the unemployed population were statistically significant (p values < 0.05) with positive coefficients in the three global models (SEM, SLM, CAR) throughout the time. The percentage of white population and obesity rate showed divergent spatial correlations at different times of the pandemic. GWR models consistently have a better model fit than global models, suggesting non-stationary correlations between a region and its neighbors. ConclusionCharacterized by temporal-geospatial patterns, disparities and their PIDRs exist in COVID-19 incidence at the county level in South Carolina. The temporal-geospatial structure of disparities and their PIDRs found in COVID-19 incidence are different from mortality and morbidity for patients who are connected with clinical care. Our findings provided important evidence for prioritizing different populations and developing tailored interventions at different times of the pandemic. These findings provided implications on containing early viral transmission and mitigating consequences of infectious disease outbreaks for possible future pandemics.

Clinical applications of neurolinguistics in neurosurgery.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.

HIV service interruptions during the COVID-19 pandemic in China: the role of HIV service challenges and institutional response from healthcare professional's perspective

BackgroundThe healthcare system in China was largely overwhelmed during the unprecedented pandemic of coronavirus disease (COVID-19). HIV-related services have been unavoidably interrupted and impacted. However, the nature and scope of HIV service interruptions due to COVID-19 has rarely been characterized in China and how HIV service challenges affect the service interruptions are also unclear. The current study aimed at characterize HIV service interruption levels and analyzed its associated factors related to service challenges and institutional response from HIV healthcare providers viewpoint. MethodsA cross-sectional online survey was conducted among 1,029 HIV healthcare providers in Guangxi, China, from April to May 2020. Latent class analysis (LCA) was first used to identify HIV service interruption levels. Then hierarchical multinomial logistic regression was conducted to analyze the relationships of HIV care service challenges and institutional response with HIV service interruption levels. Simple slope analysis was employed to examine interaction effects between HIV service challenges and institutional response to COVID-19. ResultsFour classes of HIV service interruption were identified using LCA, with 22.0% complete interruption (class 1), 15.4% moderate interruption (class 2), 21.9% minor interruption (class 3) and 40.7% almost no interruption (class 4). Using class 4 as a reference group, HIV care service challenges were positively associated with the probabilities of service interruptions (Class 1: AOR=1.23, 95%CI: 1.19[~]1.26; Class 2: AOR= 1.10, 95%CI: 1.08[~]1.13; Class 3: AOR= 1.10, 95%CI: 1.08[~]1.12). Institutional response to HIV healthcare delivery was negatively associated with the probabilities of being classified into Class 1 ("Complete interruption") (AOR=0.97, 95%CI: 0.93[~]1.00) and Class 3 ("minor interruption [Outreach service]") (AOR=0.96, 95%CI: 0.93[~]0.99) as compared to Class 4 ("almost no interruption"). Institutional response to HIV healthcare delivery moderated the association of HIV service challenges with complete interruption, but not with the moderate or minor interruption when comparing with no interruption group. ConclusionsA substantial HIV service interruptions occurs due to the COVID-19 pandemic, particularly services that require face-to-face interactions, such as VCT counselling, follow up and outreach services. HIV service challenges largely hinder the HIV service delivery. Institutional response to HIV healthcare delivery could marginally buffer the negative effect of service challenges on complete HIV service interruptions. To maintain continuity of core HIV services in face of a pandemic, build a resilient health care system with adequate preparedness is necessary.

Kinesin Family Member C1 Increases Temozolomide Resistance of Glioblastoma Through Promoting DNA Damage Repair.

Glioblastoma (GBM) is one of the most frequent primary malignant brain tumors with a poor prognosis. Unfortunately, due to the intrinsic or acquired chemoresistance of GBM cells, it easily becomes refractory disease and tumors are easy to recur. Therefore, it is critical to elucidate the molecular mechanisms underlying the chemoresistance of GBM cells to discover more efficient therapeutic treatments. Kinesin family member C1 (KIFC1) is a normal nonessential kinesin motor that affects the progression of multiple types of cancers. However, whether KIFC1 have a function in GBM is still unexplored. Here we found that KIFC1 was upregulated in human temozolomide (TMZ)-resistant GBM tissues. KIFC1 silencing is sufficient to inhibit GBM cell proliferation and amplify TMZ-induced repression of cell proliferation. Mechanistically, KIFC1 silencing contributed to DNA damage, cell cycle arrest, and apoptosis through regulating Rad51, Akt, and DNA-PKcs phosphorylation. We also noticed that KIFC1 silencing also inhibited tumor formation and increased TMZ sensitivity through regulating Ki67, Rad51, γ-H2AX, and phosphorylation of AKT in vivo. Our findings therefore confirm the involvement of KIFC1 in GBM progression and provide a novel understanding of KIFC1-Akt axis in the sensitivity of GBM to chemotherapy.

Risk perception of COVID-19 and its socioeconomic correlates in the United States: A social media analysis

Social media analysis provides a new approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) over a long enough timeframe to cover different pandemic phases. The impact of social determinants of health factors on COVID-19-related risk perceptions over time is also not clear. To address these two knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed index indicators for three dimensions of risk perceptions based on over 297 million geotagged tweets posted by over 3.5 million Twitter users from January to October 2020 in the United States. We also examined correlations between index indicator scores and county-level social determinants of health factors. The three domains of risk perceptions demonstrate different trajectories. Perceived severity kept climbing throughout the whole study period. Perceived susceptibility and negative emotion declined and remained stable at a lower level after peaking on March 11 (WHO named COVID-19 a global pandemic). Attention on risk perceptions was not exactly in accordance with epidemic trends of COVID-19 (cases, deaths). Users from socioeconomically vulnerable counties showed lower attention on perceived severity and susceptibility of COVID-19 than those from wealthier counties. Examination of trends in tweets regarding the multiple domains of risk perceptions throughout stages of the COVID-19 pandemic can help policy makers frame in-time, tailored, and appropriate responses to prevent viral spread and encourage preventive behavior uptake in United States.

Factors associated with decision making on COVID-19 vaccine acceptance among college students in South Carolina

BackgroundCOVID-19 vaccination could be a promising approach in controlling the pandemic, but its success strongly relies on the acceptance of vaccines among various populations including young adults who are especially vulnerable to COVID-19 due to their active lifestyle and perception of invulnerability. Vaccine acceptance decisions can be influenced by multiple factors and people may weigh these factors differently in their decision making. The current study aims to explore COVID-19 vaccine acceptance among college students in South Carolina and examine how they weigh these factors according to their levels of COVID-19 vaccine acceptance (i.e., acceptance, hesitance, refusal). MethodsOnline survey data were collected from 1062 college students in South Carolina between September and October 2020. Multivariate analysis of covariance was used to compare perceived importance of 12 factors affecting levels of vaccine acceptance, controlling for key demographic variables. ResultsAbout 60.6% of the college students reported they would definitely or likely take COVID-19 vaccine when available. Duration of vaccine protection, vaccine accessibility, and authoritative advice (e.g., if vaccination is recommended by school, government, or doctors) were considered important among the acceptance group; Negative consequences of vaccination and vaccine characteristics (i.e., ways the vaccine will be administered, and where the vaccine is made) were considered important by the refusal group; The hesitance group considered the same factors important as the refusal group did but also considered duration of vaccine protection and recommendation by school or doctors important. ConclusionOur findings suggest relatively low vaccine acceptance among college students in South Carolina and different factors that play a role in their vaccine uptake decision according to their levels of acceptance. Tailored vaccine promotion messages should address specific concerns among the refusal and hesitancy groups. School could play a positive role in vaccine campaign since the reluctancy group considered that recommendation by their school was important in their decision making. Health educators also need to pay particular attention to the refusal group who do not value duration of protection or authoritative advice as much as their counterparts in their vaccine decision making.

Risk exposures, risk perceptions, negative attitudes toward general vaccination, and COVID-19 vaccine acceptance among college students in South Carolina

Growing attention has been paid to vaccination in control of the COVID-19 pandemic and young adults is one of the key populations for vaccination. Advanced understanding of young adults willingness to take a COVID-19 vaccine and the potential factors influencing their vaccine intention will contribute to the development and implementation of effective strategies to promote COVID-19 vaccine uptake among this group. The current study investigated how risk exposures and risk perceptions of COVID-19 (e.g., perceived susceptibility, severity, and fear of COVID-19) as well as negative attitudes toward general vaccination were related to COVID vaccine acceptance among college students based on online survey data from 1062 college students in South Carolina. Hierarchical linear regression was used to examine the association of these factors with COVID-19 vaccine acceptance controlling for key demographics. Results suggested that perceived severity and fear of COVID-19 were positively associated with vaccine acceptance, while higher level of risk exposures (work/study place exposure) and negative attitude toward general vaccination were associated with low vaccine acceptance. Our findings suggested that we need tailored education messages for college students to emphasize the severity of COVID-19, particularly potential long-term negative consequences on health, address the concerns of side effects of general vaccines by dispelling the misconception, and target the most vulnerable subgroups who reported high level of risk exposures while showed low intention to take the vaccine. Efforts are warranted to increase college students perceived susceptibility and severity and promote their self-efficacy in health management and encourage them to take protective behaviors including vaccine uptake.