bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cognitive behavioral therapy on anxiety and depression in patients with psoriasis
Authors: Tan Chuan , Jiang Jianmei , Deng Xiaoling , Xiang Wei , Hu Tingting
Published: November 2021

Background:

Psoriasis can lead to higher social and psychological burden, and its occurrence is related to psychological disturbance. At present, there are many clinical trials on cognitive behavior therapy for depression and anxiety in patients with psoriasis. However, the results of studies vary greatly due to the different time and content of the intervention, and the curative effect is still controversial. Therefore, the purpose of this study was to explore the effect of cognitive behavior therapy on anxiety and depression in patients with psoriasis through meta-analysis.

Methods:

We searched Chinese and English databases to collect all randomized controlled trials of cognitive behavior therapy on anxiety and depression in patients with psoriasis until October 2021. Two researchers then independently screened articles, extracted data, and evaluated the quality of selected literatures. All data were processed by Stata 14.0.

Results:

The results will be published in peer-reviewed journals.

Conclusion:

Our study is expected to provide high-quality evidence-based medicine advice for the effects of cognitive behavior therapy on anxiety and depression in patients with psoriasis.

Ethics and dissemination:

Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations.

OSF REGISTRATION NUMBER:

DOI 10.17605/OSF.IO/APKVG.
Bioinformatics analyses of the pathogenesis and new biomarkers of chronic obstructive pulmonary disease
Authors: Zhang Jihua , Liu Jie , Xu Shuanglan , Yu Xiaochao , Zhang Yi , Li Xiao , Zhang Liqiong , Yang Jiao , Xing Xiqian
Published: November 2021

Background:

Chronic obstructive pulmonary disease (COPD) is one of the major cause of global death. The purpose of our analysis was to detect a more reliable biomarker and small-molecule drug candidates and to identify the precise mechanisms involved in COPD.

Methods:

Three data sets were downloaded from the Gene Expression Omnibus database and analysed by Gene Expression Omnibus 2R. Functional enrichment analyses were performed by Metascape. We use the STRING data to build a protein–protein interaction network. The targets of differentially expressed microRNA (DE miRNA) were predicted by the miRWalk database. Small-molecule drugs were predicted on connectivity map.

Results:

A total of 181 differentially expressed genes and 35 DE miRNAs were confirmed. The protein–protein interaction network including all integrated differentially expressed genes was constructed, and 4 modules were filtrated. The module genes were relative to immune, inflammatory and oxidative stress functions according to a pathway analysis. The top 20 key genes were screened. Among the DE miRNAs found to be regulating key genes, miR-194-3p, MiR-502-5p, MiR-5088-5p, MiR-3127-5p, and miR-23a-5p might be the most significant due to their high number of connecting nodes in COPD. In addition, cephaeline, emetine, gabapentin, and amrinone were found to be potential drugs to treat COPD patients.

Conclusion:

Our study suggests that miR-194-3p, miR-502-5p, and miR-23a-5p might participate in the nosogenesis of COPD. In addition, 4 potential small-molecule drugs were considered potentially useful for treating COPD patients.
Effectiveness of Chinese patent medicine in the treatment of influenza
Authors: Liu Kang , Zhang Yongkang , Song Xin
Published: November 2021

Background:

Western medicine mainly uses antiviral drugs to treat influenza. However, anti-influenza virus drugs have been reported to have high levels of drug resistance and varying degrees of adverse reactions. In addition, Western medicine uses vaccination to prevent influenza, but vaccination cannot ensure complete prevention. Vaccines have a certain lag and cannot prevent the constantly mutating influenza virus. At present, there are still certain limitations in the prevention of influenza. In recent years, traditional Chinese medicine has been used more and more widely in the prevention and treatment of influenza and improvement of influenza-like symptoms, and related clinical efficacy control studies have reached a certain number. Therefore, the purpose of this study is to systematically evaluate the effectiveness of Chinese patent medicine in the treatment of influenza.

Methods:

Computer search of PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP database, search for randomized controlled trials of Chinese patent medicines therapy on influenza, the search time limit is to build the database until October 2021. Two researchers screened the retrieved literature and collected relevant patient information and data. The final included literature was meta analyzed by Rev man5.4 software.

Results:

The effectiveness and safety of Chinese patent medicines in the treatment of patients with influenza will be systematically evaluated.

Conclusion:

Systematic collection and analysis of clinical randomized controlled trials of Chinese patent medicines for the treatment of influenza, with a view to providing basic information for clinical decision-making and related research.

Registration number:

INPLASY2021100064 (https://inplasy.com/inplasy-2021- 10-0064/).
Prognostic value of C-reactive protein to albumin ratio in metastatic colorectal cancer
Authors: Pan Yan , Lou Yinmei , Wang Lin
Published: November 2021

Background:

In recent years, several observational studies have investigated the association between C-reactive protein to albumin ratio (CAR) and prognosis of metastatic colorectal cancer (mCRC), and yielded controversial outcomes.

Methods:

Eligible studies assessing the relationship of CAR with survival and clinicopathological parameters in mCRC were searched from PubMed, Cochrane library, and Embase databases up to February 3, 2021. Overall survival (OS), progression-free survival, recurrence-free survival, and disease-free survival were synthetically calculated and compared.

Results:

A total of 6 studies including 771 patients were enrolled in this systematic review. Pooled results indicated that elevated CAR was significantly associated with poorer OS (hazard ratio: 2.393; 95% confidence interval: 1.949–2.938, P < .01) as well as decreased progression-free survival/disease-free survival/recurrence-free survival (hazard ratio: 1.731; 95% confidence interval: 1.261–2.375, P < .01). Additionally, high CAR was significantly consistent with increased modified Glasgow Prognostic Score and neutrophil–lymphocyte ratio.

Conclusion:

High CAR could be a negative prognostic marker for mCRC patients. More large-sample clinical trials are still needed to confirm the prognostic significance of CAR in mCRC.
Should synovectomy be performed during total knee arthroplasty for knee osteoarthritis
Authors: Li Mingchao , Shi Xiaoqing , Yin Songjiang , Zhang Li , Wu Peng , Liao Taiyang , Jie Lishi , Wang Peimin
Published: November 2021

Background:

To evaluate the effect of synovectomy performed during primary total knee arthroplasty for knee osteoarthritis on patients’ postoperative pain and knee function.

Methods:

We will search the following electronic databases from inception to June 2021, including PubMed, EMBASE, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Scientific Journals Database, the Wanfang database, and the Chinese Biomedicine Database. Eligible references will be all randomized controlled trials of initial total knee arthroplasty for primary knee osteoarthritis with or without synovectomy. Two reviewers will independently extract the data. Reviewer Manager 5.3 software will be used for statistical analysis.

Result:

It will provide results on the short- and long-term efficacy and safety of synovectomy in total knee arthroplasty by various comprehensive assessments.

Conclusion:

This study will provide solid evidence on whether and when synovectomy treatment should be performed during total knee arthroplasty.
Relationship between balance function and QOL in cancer survivors and healthy subjects
Authors: Morishita Shinichiro , Hirabayashi Ryo , Tsubaki Atsuhiro , Aoki Osamu , Fu Jack B. , Onishi Hideaki , Tsuji Tetsuya
Published: November 2021

A previous study reported that cancer survivors exhibit decreased postural stability compared to age-matched controls. Another study showed that cancer survivors have a lower quality of life (QOL) compared to healthy subjects, and there was a significant relationship between muscle strength and QOL in cancer survivors. We aimed to investigate differences in the associations between balance function and QOL in cancer survivors and healthy subjects.

Forty-one cancer survivors and 33 healthy subjects were included. Balance function was evaluated using the timed up and go test, and body sway was tested using a force platform. QOL was assessed using the medical outcome study 36-item short-form health survey.

Cancer survivors exhibited significantly higher timed up and go and lower QOL than that of healthy subjects (P < .05). There was a significant association between body sway and QOL (P < .05) among cancer survivors. However, healthy subjects had subscales for QOL related to the body sway test parameters more frequently than cancer survivors (P < .05).

Cancer survivors’ balance function may have little effect on QOL, unlike in healthy subjects.
Depression and quality of life in Brazilian and Portuguese older people communities
Authors: da Silva Dantas Bruno Araújo , Cavalcante Anna Carolyna Vieira , de Miranda Jéssica Maria Arouca , da Silva Toscano Gislani Acásia , Nobre Thaiza Teixeira Xavier , Mendes Felismina Rosa Parreira , de Miranda Francisco Arnoldo Nunes , Maia Eulália Maria Chaves , Torres Gilson de Vasconcelos
Published: November 2021

We aimed to compare the association of depression with aspects of quality of life (QoL) among older people users of primary health care (PHC) living in Brazil and Portugal.

We carried out an observational, cross-sectional and comparative study with a quantitative approach in the PHC scope in Brazil and Portugal, where we obtained a nonrandom sample of 150 participants aged 65 years or older (100 Brazilians and 50 Portuguese). We used the socioeconomic and health data questionnaire, the Medical Outcomes Short-Form Health Survey QoL (SF-36) questionnaire and the Beck Inventory.

Among the socioeconomic profiles, most were females aged between 65 and 80 years in both countries. There was a significant difference between groups in the income variable, with 100.0% of Portuguese people earning up to 1 minimum wage (P value <.001), and the presence of chronic diseases in 92.0% of respondents in Portugal (P value = .033). In the association analysis, most aspects of QoL had a higher median score (>50.0) within the categorical variables of “absent” and “mild” depression. The Emotional role functioning, Physical role functioning, Physical functioning, Mental health, Total score domains and the Mental health and Physical health summary measures stood out with this behavior in Brazil and in Portugal, where these latter 2 presented moderate to strong correlation values (ρ > 0.400) in Portugal. Greater associations of depression on QoL were revealed in Portugal than in Brazil. Among their most expressive associations, the Physical role functioning (odds ratio [OR] = 4.776; 95.0% confidence interval [CI]: 2.41–9.43), Physical functioning (OR = 3.037; 95.0% CI: 3.037), Vitality (OR = 6.000; 95.0% CI: 1.56–23.07) and Total score (OR = 3.727; 95.0% CI: 2.24–6.17) domains and the Mental health summary measure (OR = 3.870; 95.0% CI: 2.13–7.02) stood out.

Aspects related to the emotional, physical, functional and mental health components stood out. The association and correlation with depression were more expressive in Portugal compared to Brazil. However, similar results were obtained in Brazil but with less relevance.
Early outcomes of endoscopic endonasal approach pituitary adenomas resection with minimal nasal injury
Authors: Tao Chao , Cheng Gang , Chen Yunxiang , Gu Peiyuan , Hu Weixing
Published: November 2021

To report the results of a consecutive series of pituitary adenomas resected through endoscopic endonasal approach (EEA) with minimal nasal injury.

Retrospectively review tumor characteristics and surgical outcomes of a consecutive series of EEA pituitary adenomas resection performed mainly by a single author between March 2018 and June 2019.

A total of 75 endoscopic endonasal approach pituitary adenoma resections were performed by the authors’ team. Of the 75 patients, 28 through mononostril EEA, 47 through Binonostril EEA. Hadad-Bassagasteguy vascularized nasoseptal flap was harvested in only 4 (5.3%) patients with a high risk of postoperative cerebrospinal fluid leak, and one side middle turbinate only been resected in 2 (2.7%) patients, other patients preserved bilateral middle turbinate. Of the 75 patients, gross total resection is 74.7%, near-total resection is 16.0%. Endocrinological remission was achieved in 76.9% of GH-secreting adenomas, 61.5% of prolactin-secreting adenomas. The postoperative cerebrospinal fluid leak rate was 2.7%. Two patients had suprasellar hemorrhage, 1 patient had perioperative stroke, 2 patients had permanent diabetes insipidus, no cranial nerve deficits, internal carotid artery injury, anosmia, and death. The sino-nasal function was measured with the Sino-Nasal Outcome Test-22 and visual analog scale for olfaction preoperatively and postoperatively, and there was no statistically significant difference.

The EEA is an effective approach to resect pituitary adenomas, the gross total resection and near-total resection rate and endocrinological remission rate are satisfactory. The EEA is a safe approach, as the complication rate is acceptable compared with those reported in the previous series of microscopic and endoscopic approaches. These results can be achieved with minimal nasal injury.
Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD
Authors: Yuan Danfeng , Zhang Manxue , Huang Yan , Wang Xinwei , Jiao Jian , Huang Yi
Published: November 2021

Background:

Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.

Methods:

Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.

Results:

This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).

Conclusion:

Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.

Registration: PROSPERO (no. CRD42021265830).
Efficacy of sequential N-butylphthalide therapy on psychiatric and behavioral functions in acute ischemic stroke
Authors: Yang Le , Li Hui , Wu Yanzhi , Zhang Hongdan , Du Jieqiong , Chen Yankun
Published: November 2021

Background:

Stroke can cause physical and mental problems. This study examined how the sequential therapy of N-butylphthalide (NBP) could effectively improve physical movement, life activities, and psychological disorders in stroke patients.

Methods:

This double-blind, randomized controlled trial included middle-aged or elderly patients with acute ischemic stroke that had commenced within 48 hours before enrolment in the study. The experimental group was administered 100 mL NBP injections twice a day in the first 14 days, and a sequential 200 mg NBP soft capsule 3 times a day for the next 76 days. The control group was administered 100 mL NBP placebo injections twice a day in the first 14 days and 200 mg sequential NBP placebo soft capsule 3 times a day for the next 76 days. Primary outcomes were the National Institutes of Health Stroke Scale, the Barthel Index of activities of daily living, and Modified Rankin Scale which were evaluated at day 0, day 14, and month 1 or at day 14, month 3, and month 6. Secondary outcomes included the Hamilton Anxiety Scale and the Hamilton Depression Scale, all were evaluated on day 0, month 3, and month 6. Moreover, the adverse reaction of NBP or other serious adverse events were evaluated at each time.

Results:

Our therapy significantly increased the Barthel Index of activities of daily living scores, decreased the National Institutes of Health Stroke Scale and Modified Rankin Scale scores, and the incidence of the Hamilton Anxiety Scale and the Hamilton Depression Scale of ischemic stroke patients (P < .05).

Conclusion:

Our results indicated that 90 days’ sequential therapy with NBP as an additional therapy in the treatment of ischemic stroke can better improve patients’ psychological and behavioral functions without significant side effects.
Interventional treatment for acute cerebral infarction with large vessel occlusion combined with aortic arch interruption
Authors: Zhang WenSheng , Xing WeiFang , Zhu MinZhen , Zhong XiaoJing , He JinZhao
Published: November 2021

Rationale:

Aortic arch interruption is a type of congenital vascular malformation that is often observed in childhood. Most children die of congestive heart failure due to rapid deterioration. Children can only survive to adulthood if they have extremely rich collateral circulation. Cases of acute cerebral infarction with large vessel occlusion receiving interventional treatment in adult patients with interrupted aortic arch have not been reported.

Patient concerns:

A 55-year-old man with a history of atrial fibrillation and smoking but without a family history of stroke was admitted to our hospital with a 5-hour history of left limb weakness and speech difficulties.

Diagnoses:

Emergency brain computed tomography showed a large cerebral infarction in the right frontal temporal parietal lobe. He was suspected to have aortic arch interruption in the early stage of endovascular interventional therapy through the femoral artery approach, and was converted to the transradial artery pathway. The aortic arch was disconnected, and the right internal carotid artery was occluded.

Interventions:

Considering the possibility of cardiogenic embolism, a middle catheter was used for thrombus aspiration of the right internal carotid artery. After removal of the dark red thrombus was removed, the right internal carotid artery was successfully recanalized.

Outcomes:

The patient recovered well after the operation. However, the patient and his family refused further treatment for aortic arch interruption. The modified Rankin Scale score was 0 at 3 months and 1 year of follow-up which meant that he recovered quite well.

Lessons:

Adult patients with acute cerebral infarction with large vessel occlusion are rarely complicated with aortic arch interruption, and emergency thrombectomy via the radial artery approach is feasible.
Hereditary paraganglioma presenting with atypical symptoms
Authors: Eguchi Shu , Ono Rintaro , Sato Takeshi , Yada Keigo , Umehara Naoki , Narumi Satoshi , Ichihashi Yosuke , Nozaki Taiki , Kanomata Naoki , Hasegawa Tomonobu , Ozawa Miwa , Hasegawa Daisuke
Published: November 2021

Rationale:

Paraganglioma (PGL), an extra-adrenal pheochromocytoma, is a rare tumor, especially in children. While hypersecretion of catecholamines causes the classic triad of headaches, palpitations, and profuse sweating, prompt diagnosis is still challenging.

Patient concerns:

For 7 months, an 8-year-old boy complained of polyuria and weight loss, followed by proteinuria and headache for 1 month prior to admission. He was admitted to our hospital due to an afebrile seizure.

Diagnosis:

His blood pressure remained markedly elevated even after cessation of the convulsion. Magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Abdominal computed tomography showed a mass lesion encasing the left renal artery, measuring 41 mm in length along its major axis. The plasma and urine levels of normetanephrine were elevated. Additionally, iodine-123-metaiodobenzylguanidine scintigraphy showed an abnormal uptake in the abdominal mass with no evidence of metastasis. Based on these findings, we tentatively diagnosed him with PGL.

Intervention:

Substantial alpha- and beta-blocking procedures were performed, followed by a tumor resection and an extended left nephrectomy on day 31 of hospitalization. Pathological findings confirmed the diagnosis of PGL.

Outcome:

The postoperative course was uneventful, and his blood pressure normalized without the use of antihypertensive agents. Genetic testing revealed a known SDHB germline mutation. The same mutation was also detected on his father and paternal grandfather without any history of hypertension or malignant tumor.

Lesson:

It remains challenging to diagnose pheochromocytoma/paraganglioma (PPGL) promptly because PPGL can present with a variety of symptoms. Preceding symptoms of the presented case might be caused by PGL. Although PPGL is a rare disease, especially in children, it should be considered in differential diagnosis when various unexplained symptoms persist.
A case report of early application of veno-arterial extracorporeal membrane oxygenation in amniotic fluid embolism
Authors: Ge Chen , Liu Junhang , Fu You , Jia Lijing , Bai Yinxiang , Yang Zhiwei , Du Quansheng
Published: November 2021

Rationale:

Amniotic fluid embolism (AFE) is a rare obstetrical complication and is a leading cause of maternal death in developed countries. Despite the development of supportive therapeutic measures, the mortality rate remains high.

Patient concerns:

A 38-year-old nulliparous pregnant woman, who underwent in vitro fertilization-embryo transfer, was admitted for labor at 37 weeks’ gestation. Approximately 30 minutes after delivery of the placenta, the puerpera developed postpartum hemorrhage with uterine atony. Soon after, the patient experienced hypotension, repeated cardiac arrest, refectory hypoxia, and disseminated intravascular coagulopathy.

Diagnosis:

AFE is diagnosed clinically. The pregnant woman in this case fulfilled the diagnostic criteria for AFE: acute hypotension, cardiac arrest, acute hypoxia, and coagulation disorders within approximately 30 minutes after delivery of the placenta.

Interventions:

The patient was intubated, connected to a ventilator, and was administered a high dose of vasoactive drugs to maintain blood pressure and underwent an emergency hysterectomy. Considering the risk for recurrent cardiac arrest and severe refractory hypoxia, venoarterial extracorporeal membrane oxygenation was initiated and discontinued as soon as cardiac function was restored based on serial bedside ultrasound assessment.

Outcomes:

The patient stabilized on day 7 in the intensive care unit and was transferred to the obstetrics ward and, 1 week later, was discharged with no complications. Two months later, follow-up revealed that the patient was in good condition.

Lesson:

Serial bedside ultrasound was crucial for assessing cardiac function and optimal weaning. Timely application of venoarterial extracorporeal membrane oxygenation and weaning was significant to avoid the occurrence of complications and improve long-term outcomes.
Differential diagnosis of thymic epithelial neoplasms on computed tomography using the diameter of the thymic vein
Authors: Sakamoto Naoya , Kurokawa Ryo , Watadani Takeyuki , Morikawa Teppei , Nakaya Moto , Cho Shinichi , Fujita Nana , Kamio Satoru , Koyama Hiroaki , Suzuki Satoshi , Yamada Haruyasu , Abe Osamu , Gonoi Wataru
Published: November 2021

Although differentiating benign and malignant thymic epithelial lesions is important to avoid unnecessary treatment and predict prognosis, it is challenging because of overlaps in the chest computed tomography (CT) findings. In this study, we investigated whether the diameter of the thymic vein and other CT findings could differentiate between benign (thymoma and thymic cysts) and malignant (thymic carcinoma, [TCa]) lesions.

We conducted a retrospective study across two tertiary referral hospitals in Japan between November 2009 and June 2018. We included 12 patients with TCa, 34 patients with thymomas, and 17 patients with thymic cysts. We analyzed the receiver operating characteristic (ROC) curve to determine the best cut-off values and performed univariate and multivariate analyses of CT findings to distinguish TCa from other benign lesions. Post-hoc analysis was performed for the maximum short axis of the thymic vein using the Mann–Whitney U test, and the number of the maximum short axis of the thymic vein ≥ the cutoff was determined using the Fisher exact test with a family-wise error-correction using Bonferroni's method.

ROC analysis showed that a maximum short axis of the thymic vein ≥2 mm was considerably more frequent in TCa than in the other lesions (P < .001 for both), with 83% sensitivity and 86% specificity. Univariate and multivariate analyses revealed the association with TCa of the number of the maximum short axis of the thymic vein ≥2 mm (P = .005, multivariate generalized linear model analysis), ill-defined margin (P = .001), and mediastinal lymphadenopathy (P < .001). Thymic vein diameter was in descendimg order of TCa > thymoma > thymic cysts with statistically significant differences between the groups (Ps < .05).

Thymic vein diameter was significantly longer in TCa than in thymoma and thymic cysts. Measurement of the maximum short axis of the thymic vein could be a powerful diagnostic tool to differentiate TCa from thymoma and thymic cysts.
A Replicable, Solution-Focused Approach to Cross-Sector Data Sharing for Evaluation of Community Violence Prevention Programming
Authors: Mayfield Carlene A. , Siegal Rachel , Herring Melvin , Campbell Tracie , Clark Catie L. , Langhinrichsen-Rohling Jennifer
Published: November 2021

Context:

Community violence is a public health problem that erodes social infrastructure. Structural racism contributes to the disparate concentration of violence in communities of color. In Mecklenburg County, North Carolina, increasing trends in community violence show racial and geographic disparities that emphasize the need for cross-sector, data-driven approaches to program and policy change. Cross-sector collaborations are challenged by data sharing barriers that hinder implementation.

Program:

In response to community advocacy, Mecklenburg County Public Health (MCPH) launched a Community Violence Prevention Plan with evidence-based programming. The Cure Violence (CV) model, a public health approach to disrupting violence through equitable resource provision, network building, and changing norms, was implemented at the community level. The Health Alliance for Violence Intervention (HAVI) model, a hospital-based screening and case management intervention for victims of violence, was implemented at Carolinas Medical Center in Charlotte, the region's only level I trauma center.

Methods:

A data collaborative was created to optimize evaluation of CV and HAVI programs including MCPH, the city of Charlotte, Atrium Health, Charlotte-Mecklenburg Schools, Johnson C. Smith University, and the University of North Carolina Charlotte. A comprehensive approach to facilitate data sharing was designed with a focus on engaging stakeholders and generating solutions to commonly reported barriers. Structured interviews were used to inform a solution-focused strategy.

Results:

Stakeholders reported perceptions of their organization's barriers and facilitators to cross-sector data sharing. Common technology, legal, and governance barriers were addressed through partnership with a local integrated data system. Solutions for trust and motivational challenges were built into ongoing collaborative processes.

Discussion:

Data silos inhibit the understanding of complex public health issues such as community violence, along with the design and evaluation of collective impact efforts. This approach can be replicated and scaled to support cross-sector collaborations seeking to influence social and health inequities stemming from structural racism.
The Massachusetts Racial Equity Data Road Map: Data as a Tool Toward Ending Structural Racism
Authors: Manning Susan E. , Blinn Antonia M. , Selk Sabrina C. , Silva Christine F. , Stetler Katie , Stone Sarah L. , Yazdy Mahsa M. , Bharel Monica
Published: November 2021

Background:

In 2015, the Massachusetts Department of Public Health (MDPH) adopted a Title V maternal and child health priority to “promote health and racial equity by addressing racial justice and reducing disparities.” A survey assessing staff capacity to support this priority identified data collection and use as opportunities for improvement. In response, MDPH initiated a quality improvement project to improve use of data for action to promote racial equity.

Methods:

MDPH conducted value stream mapping to understand existing processes for using data to inform racial equity work. Key informant interviews and a survey of program directors identified challenges to using data to promote racial equity. MDPH used a cause-and-effect diagram to identify and organize challenges to using data to inform racial equity work and better understand opportunities for improvement and potential solutions.

Results:

Key informants highlighted the need to consider structural factors and historical and community contexts when interpreting data. Program directors noted limited staff time, lack of performance metrics, competing priorities, low data quality, and unclear expectations as challenges. To address the identified challenges, the team identified potential solutions and prioritized development and piloting of the MDPH Racial Equity Data Road Map (Road Map).

Conclusions:

The Road Map framework provides strategies for data collection and use that support the direction of actionable data-driven resources to racial inequities. The Road Map is a resource to support programs to authentically engage communities; frame data in the broader contexts that impact health; and design solutions that address root causes. With this starting point, public health systems can work toward creating data-driven programs and policies to improve racial equity.
Early Treatment With a Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates the Brain Transcriptome to Create Neuroprotective Changes in a Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock
Authors: Bambakidis Ted , Dekker Simone E. , Williams Aaron M. , Biesterveld Ben E. , Bhatti Umar F. , Liu Baoling , Li Yongqing , Pickell Zachary , Buller Benjamin , Alam Hasan B.
Published: November 2021

Background:

Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS.

Methods:

Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 h of shock, animals were randomized (n = 4/group) to treatment with either lactated Ringer's (LR) or LR + EV. Both groups received fluid resuscitation after 2 h of shock, and autologous packed red blood cells 5 h later.

After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data were imported into the iPathway pipeline for bioinformatics analyses.

Results:

5,273 genes were differentially expressed in the LR + EV group versus LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation.

Conclusions:

In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment.
Field surveys in Croatia and North Macedonia reveal two novel phleboviruses circulating in sandflies
Authors: Ayhan Nazli , Alten Bulent , Ivovic Vladimir , Cvetkovikj Aleksandar , Stefanovska Jovana , Martinkovic Franjo , Piorkowski Geraldine , Moureau Gregory , Gould Ernest A. , Pettersson John H.-O. , de Lamballerie Xavier , Charrel Remi N.
Published: November 2021

Sandfly-borne phleboviruses are distributed widely throughout the Mediterranean Basin, presenting a threat to public health in areas where they circulate. However, the true diversity and distribution of pathogenic and apathogenic sandfly-borne phleboviruses remains a key issue to be studied. In the Balkans, most published data rely on serology-based studies although virus isolation has occasionally been reported. Here, we report the discovery of two novel sandfly-borne phleboviruses, provisionally named Zaba virus (ZABAV) and Bregalaka virus (BREV), which were isolated in Croatia and North Macedonia, respectively. This constitutes the first isolation of phleboviruses in both countries. Genetic analysis based on complete coding sequences indicated that ZABAV and BREV are distinct from each other and belong to the genus Phlebovirus, family Phenuiviridae. Phylogenetic and amino acid modelling of viral polymerase shows that ZABAV and BREV are new members of the Salehabad phlebovirus species and the Adana phlebovirus species, respectively. Moreover, sequence-based vector identification suggests that ZABAV is mainly transmitted by Phlebotomus neglectus and BREV is mainly transmitted by Phlebotomus perfiliewi. BREV neutralizing antibodies were detected in 3.3% of human sera with rates up to 16.7% in certain districts, demonstrating that BREV frequently infects humans in North Macedonia. In vitro viral growth kinetics experiments demonstrated viral replication of both viruses in mammalian and mosquito cells. In vivo experimental studies in mice suggest that ZABAV and BREV exhibit characteristics making them possible human pathogens.
Genetic relationships between efficiency traits and gut microbiota traits in growing pigs fed a conventional or a high fiber diet
Authors: Déru V. , Bouquet A. , Zemb O. , Blanchet B. , De Almeida M.L , Cauquil L. , Carillier-Jacquin C. , Gilbert H.
Published: November 2021

In pigs, the gut microbiota composition plays a major role in the process of digestion, but is influenced by many external factors, especially diet. To be used in breeding applications, genotype by diet interactions on microbiota composition have to be quantified, as well as their impact on genetic covariances with feed efficiency (FE) and digestive efficiency (DE) traits. This study aimed at determining the impact of an alternative diet on variance components of microbiota traits (genera and alpha diversity indices), and estimating genetic correlations between microbiota and efficiency traits for pigs fed a conventional (CO) or a high fiber (HF) diet. Fecal microbes of 812 full-siblings fed a CO diet and 752 pigs fed the HF diet were characterized at 16 weeks of age by sequencing the V3-V4 region of the 16S rRNA gene. A total of 231 genera were identified. Digestibility coefficients of nitrogen, organic matter and energy were predicted analyzing the same fecal samples with near infrared spectrometry. Daily feed intake, feed conversion ratio, residual feed intake and average daily gain (ADG) were also recorded. The 71 genera with less than 20% of zeros were retained for genetic analyses. Heritability (h2) of microbiota traits were similar between diets (from null to 0.38 ± 0.12 in the CO diet and to 0.39 ± 0.12 in the HF diet). Only three out of the 24 genera and two alpha diversity indices with significant h2 in both diets had genetic correlations across diets significantly different from 0.99 (P < 0.05), indicating limited genetic by diet interactions for these traits. When both diets were analyzed jointly, 59 genera had h2 significantly different from zero. Based on the genetic correlations between these genera and ADG, FE and DE traits, three groups of genera could be identified. A group of 29 genera was favorably correlated with DE and FE traits, 14 genera were unfavorably correlated with DE traits, and the last group of 16 genera had correlations close to zero with production traits. However, genera favorably correlated with DE and FE traits were unfavorably correlated with ADG, and vice versa. Alpha diversity indices had correlation patterns similar to the first group. In the end, genetic by diet interactions on gut microbiota composition of growing pigs were limited in this study. Based on this study, microbiota-based traits could be used as proxies to improve FE and DE in growing pigs.
Weighing the DNA content of Adeno-Associated Virus vectors with zeptogram precision using nanomechanical resonators
Authors: Katsikis Georgios , Hwang Iris E. , Wang Wade , Bhat Vikas S. , McIntosh Nicole L. , Karim Omair A. , Blus Bartlomiej J. , Sha Sha , Agache Vincent , Wolfrum Jacqueline M. , Springs Stacy L. , Sinskey Anthony J. , Barone Paul W. , Braatz Richard D. , Manalis Scott R.
Published: November 2021

Quantifying the composition of viral vectors used in vaccine development and gene therapy is critical for assessing their functionality. Adeno-Associated Virus (AAV) vectors, which are the most widely used viral vectors for in-vivo gene therapy, are typically characterized using PCR, ELISA, and Analytical Ultracentrifugation which require laborious protocols or hours of turnaround time. Emerging methods such as Charge-Detection Mass Spectroscopy, Static Light Scattering, and Mass Photometry offer turnaround times of minutes for measuring AAV mass, but mostly require purified AAV-based reference materials for calibration. Here, we demonstrate a method for using Suspended Nanomechanical Resonators (SNR) to directly measure both AAV mass and aggregation from a few microliters of sample within minutes. We achieve a resolution near 10 zeptograms which corresponds to 1% of the genome holding capacity of the AAV capsid. Our results show the potential of our method for providing real-time quality control of viral vectors during biomanufacturing.
Affinity Scores: An Individual-centric Fingerprinting Framework for Neuropsychiatric Disorders
Authors: Wannan Cassandra M J , Pantelis Christos , Merritt Antonia , Tonge Bruce , Syeda Warda T
Published: November 2021

Background

Population-centric frameworks of biomarker identification for psychiatric disorders focus primarily on comparing averages between groups and assume that diagnostic groups are (1) mutually-exclusive, and (2) homogeneous. There is a paucity of individual-centric approaches capable of identifying individual-specific ‘fingerprints’ across multiple domains. To address this, we propose a novel framework, combining a range of biopsychosocial markers, including brain structure, cognition, and clinical markers, into higher-level ‘fingerprints’, capable of capturing intra-illness heterogeneity and inter-illness overlap.

Methods

A multivariate framework was implemented to identify individualised patterns of brain structure, cognition and clinical markers based on affinity to other participants in the database. First, individual-level affinity scores defined each participant’s “neighbourhood” across each measure based on variable-specific hop sizes. Next, diagnostic verification and classification algorithms were implemented based on multivariate affinity score profiles. To perform affinity-based classification, data were divided into training and test samples, and 5-fold nested cross-validation was performed on the training data. Affinity-based classification was compared to weighted K-nearest neighbours (KNN) classification. K-means clustering was used to create clusters based on multivariate affinity score profiles. The framework was applied to the Australian Schizophrenia Research Bank (ASRB) dataset.

Results

Individualised affinity scores provided a ‘fingerprint’ of brain structure, cognition, and clinical markers, which described the affinity of an individual to the representative groups in the dataset Diagnostic verification capability was moderate to high depending on the choice of multivariate affinity metric. Affinity score-based classification achieved a high degree of accuracy in the training, nested cross-validation and prediction steps, and outperformed KNN classification in the training and test datasets.

Conclusion

Affinity scores demonstrate utility in two keys ways: (1) Early and accurate diagnosis of neuropsychiatric disorders, whereby an individual can be grouped within a diagnostic category/ies that best matches their fingerprint, and (2) identification of biopsychosocial factors that most strongly characterise individuals/disorders, and which may be most amenable to intervention.
Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology
Authors: Sorokin Elena P. , Basty Nicolas , Whitcher Brandon , Liu Yi , Bell Jimmy D. , Cohen Robert L. , Cule Madeleine , Thomas E. Louise
Published: November 2021

The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank using magnetic resonance imaging, and provide the first reference range for spleen iron in an unselected population. Through genome-wide association study, we identify associations between spleen iron and regulatory variation at two hereditary spherocytosis genes, ANK1 and SPTA1. Spherocytosis-causing coding mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while these novel common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes that have been observed clinically. Our genetic study also identifies a signal which co-localizes with a splicing quantitative trait locus for MS4A7, and we show this gene is abundantly expressed in the spleen and in macrophages. The combination of deep learning and efficient image processing enables non-invasive measurement of spleen iron and, in turn, characterization of genetic factors related to iron recycling and erythrocyte morphology.
HSP90 modulates T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages
Authors: Carey Ryan M. , Hariri Benjamin M. , Adappa Nithin D. , Palmer James N. , Lee Robert J.
Published: November 2021

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including some secreted by Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO enhances mucociliary clearance and has direct antibacterial effects in ciliated epithelial cells and increases phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.
Characterizing Protein Conformational Spaces using Dimensionality Reduction and Algebraic Topology
Authors: Joshi Arpita , Haspel Nurit , González Eduardo
Published: November 2021

Datasets representing the conformational landscapes of protein structures are high dimensional and hence present computational challenges. Efficient and effective dimensionality reduction of these datasets is therefore paramount to our ability to analyze the conformational landscapes of proteins and extract important information regarding protein folding, conformational changes and binding. Representing the structures with fewer attributes that capture the most variance of the data, makes for quicker and precise analysis of these structures. In this work we make use of dimensionality reduction methods for reducing the number of instances and for feature reduction. The reduced dataset that is obtained is then subjected to topological and quantitative analysis. In this step we perform hierarchical clustering to obtain different sets of conformation clusters that may correspond to intermediate structures. The structures represented by these conformations are then analyzed by studying their high dimension topological properties to identify truly distinct conformations and holes in the conformational space that may represent high energy barriers. Our results show that the clusters closely follow known experimental results about intermediate structures, as well as binding and folding events.