bluuebunny/crossref_metadata_2025 huggingface dataset:
Research trends of platelet-rich plasma therapy on knee osteoarthritis from 2011 to 2021: A review
Authors: Cui Yubo , Lin Liqiong , Wang Zhiwei , Wang Kai , Xiao Lili , Lin Wentao , Zhang Yiyuan
Published: January 2023

Background:

Platelet-rich plasma (PRP) has been widely used to alleviate osteoarthritis of the knee, and research results are abundant. However, there are no bibliometric reports in publications in this field. Therefore, the current status of PRP for the treatment of osteoarthritis of the knee from 2011 to 2021 was analyzed using Citespace 6.1.R2 software.

Methods:

Publications regarding PRP treating Knee Osteoarthritis between 2011 and 2021 were extracted from the Web of Science database. CiteSpace was used to analyze the number of publications, countries, institutions, journals, authors, cited references, and keywords by using standard bibliometric indicators.

Results:

A total of 988 publications were searched from 2011 to 2021. In the last decade, the number of publications has increased in the field. Brian J. Cole was the author with the most output, with 31 relevant articles, and Giuseppe Filardo ranked first in cited authors. Am J Sport Med was the most cited journal. In this field, the most prolific country is the United States and the most prolific institution is Rush University. An article published by Sandeep Patel ranked first in cited references with 118 citations. “Randomized controlled trial” was the most bursting keyword and other more popular keywords about PRP for knee osteoarthritis: “hyaluronic acid,” “double-blind,” and “mesenchymal stem cell.”

Conclusion:

This bibliometric study provides a decade of current clinical research on PRP for the treatment of osteoarthritis of the knee, which can help researchers understand the hot spots in the field and provide a new direction for their research.
Critical digital ischemia and biliary cholangitis related to graft versus host disease: A case report and systematic literature review
Authors: Hidalgo Calleja Cristina , Montilla Morales Carlos Alberto , Sánchez González María Dolores , Pastor Navarro Sonia , Ibáñez Martínez Marta , Conde Ferreiros Alberto , López Corral Lucía
Published: January 2023

Rationale:

Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and remains the leading cause of late morbidity and mortality. cGVHD involves a heterogeneous group of organic manifestations, many of which mimic autoimmune diseases such as scleroderma, primary biliary cholangitis, Sjögren syndrome and polymyositis.

Patient concerns:

A 60-years-old female with a history of allo-HCT developed de novo cGVHD 11 months after allo-HCT with isolated liver involvement. The patient presented with jaundice, cytolysis, cholestasis and concomitant acute digital ischemia. Liver biopsy and autoimmunity tests were performed and were found to be compatible with immune-mediated liver damage. Nailfold capillaroscopy revealed microangiopathy, characterized by avascular areas and some enlarged capillaries resembled an early systemic sclerosis pattern.

Diagnosis:

Biliary cholangitis-like and digital ischemia related to cGVHD.

Interventions:

The patient was treated with high-dose prednisone and ursodeoxycholic acid, and extracorporeal photopheresis. The patient required hospital admission for administration of intravenous prostacyclin due to refractory Raynaud syndrome.

Outcomes:

After 6 to 8 weeks, the patient achieved a good response, with evident clinical improvement and progressive normalization of liver function.

Lessons:

cGVHD is a multiorgan pathological condition, and this case emphasizes that a multidisciplinary team, including rheumatologists, should be involved in the follow-up of allo-transplant patients to ensure that the clinical complications are adequately addressed. Early intervention is critical for improving patient’ prognosis.

In addition, we performed a systemic literature review based on published case articles on hepatic cGVHD and digital ischemia published up to August 2022. To the best of our knowledge, this is the first reported case of such an association.
A leading bibliometric author does not have a dominant contribution to research based on the CJAL score: Bibliometric analysis
Authors: Tam Hon-Pheng , Hsieh Wan-Ting , Chien Tsair-Wei , Chou Willy
Published: January 2023

Background:

A total of 22,367 bibliometric articles have been indexed by Web of Science (WoS). The most significant contribution to the field has not yet been identified through bibliometric analysis. A comparison of individual research achievements (IRAs) and trend analysis of article citations are required after extracting bibliometric articles. The study aimed to confirm whether the leading author has a dominant RA and which articles are worth reading for readers using trend analysis.

Methods:

We identified authors with at least 100 articles related to bibliometrics in the WoS core collection. A total of 399 articles were collected to cluster author collaborations. Co-word analysis and chord diagrams were used to match chief authors in clusters with Keywords Plus in WoS core collection. The category, journal impact factor, authorship, and L-index (CJAL) score and the absolute advantage coefficient (AAC) were used to compare IRAs and identify the leading author who dominated the field significantly beyond the next 2 authors. In addition to network charts and chord diagrams, 4 visualizations were used to report study results, including a Sankey diagram, a dot plot, a temporal trend graph, and a radar plot. The temporal bubble graph was used to select articles that deserve to be read.

Results:

The top 3 authors were Lutz Bornmann, Yuh-Shan Ho, and Giovanni Abramo, with CJAL scores of 176.22, 176.02, and 112.06, respectively, from Germany, Italy, and Taiwan. Based on the weak dominance coefficient (AAC = 0.20 < 0.70), it is evident that the leading bibliometric author has no such significant power beyond the next 2 leading authors in IRAs. A trend analysis of the last 4 years was used to illustrate the 2 articles that deserve to be read.

Conclusion:

Three leading authors were identified through a co-word analysis of bibliometrics. There was no evidence of an author who possessed a dominant position due to a lower AAC on the leading author. The CJAL score and the AAC can be applied to many bibliographical studies in the future rather than being limited to bibliometric studies that evaluate the leading authors in a field, as we did in this study.
Application of transperineal ultrasound combined with shear wave elastography in pelvic floor function assessment after hysterectomy
Authors: Ji Runyan , He Bosheng , Wu Jing
Published: January 2023

This study explored the application of transperineal ultrasound (TPUS) combined with shear wave elastography (SWE) in evaluating the pelvic structure function of women after total hysterectomy. Seventy healthy women and 76 women who underwent total hysterectomy were selected for ultrasound examination. They were divided into normal (nulliparous) group, (parous) group without hysterectomy, and (parous) group with hysterectomy. TPUS combined with SWE was used to evaluate the pelvic floor structure and function in the 3 groups of women. Posterior urethrovesical angle in resting and maximal Valsalva state, anteroposterior diameter of hiatus in the 3 states, the bladder neck descent, the urethral rotation angle, the Young modulus of left and right puborectalisis muscle in resting state, and the incidence of pelvic floor dysfunction diseases were all higher in the group with hysterectomy than in the group without hysterectomy (P < .05). Bladder neck-symphyseal distance and anorectal junction-symphyseal distance in the maximum Valsalva state, and the difference in Young modulus between the left and right PR before and after anus contraction were all lower in the group with hysterectomy than the group without hysterectomy (P < .05). The incidence of pelvic floor dysfunction in postmenopausal patients in the group with hysterectomy was higher than that in premenopausal patients (P < .05). Total hysterectomy had negative effects on female pelvic floor structure and function. TPUS combined with SWE can be used to evaluate pelvic floor function in multiple dimensions.
Diagnostic model for preschool workers’ unwillingness to continue working: Developed using machine-learning techniques
Authors: Matsuo Moemi , Matsumoto Koutarou , Higashijima Misako , Shirabe Susumu , Tanaka Goro , Yoshida Yuri , Higashi Toshio , Miyabara Hiroya , Komatsu Youhei , Iwanaga Ryoichiro
Published: January 2023

The turnover of kindergarten teachers has drastically increased in the past 10 years. Reducing the turnover rates among preschool workers has become an important issue worldwide. Parents have avoided enrolling children in preschools due to insufficient care, which affects their ability to work. Therefore, this study developed a diagnostic model to understand preschool workers’ unwillingness to continue working. A total of 1002 full-time preschool workers were divided into 2 groups. Predictors were drawn from general questionnaires, including those for mental health. We compared 3 algorithms: the least absolute shrinkage and selection operator, eXtreme Gradient Boosting, and logistic regression. Additionally, the SHapley Additive exPlanation was used to visualize the relationship between years of work experience and intention to continue working. The logistic regression model was adopted as the diagnostic model, and the predictors were “not living with children,” “human relation problems with boss,” “high risk of mental distress,” and “work experience.” The developed risk score and the optimal cutoff value were 14 points. By using the diagnostic model to determine workers’ unwillingness to continue working, supervisors can intervene with workers who are experiencing difficulties at work and can help resolve their problems.
Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis
Authors: Huang Zhihao , Xu Xinru , Xu Dan , Zhao Pengfei , Zou Miao
Published: January 2023

Background:

To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty.

Methods:

PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software.

Results:

A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05).

Conclusion:

Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty.
Association between serum amylase levels and CD4 cell counts in newly diagnosed people living with HIV: A case-control study
Authors: Jin Yong , Yang Tianmeng , Xia Ting , Shen Zhihong , Ma Tingting
Published: January 2023

Serum amylase is a direct reflection of pancreatic injury. Several clinical studies have indicated that antiretroviral therapy may be the main cause of increased serum amylase in people living with human immunodeficiency virus (PLWH). However, other probable causes including direct human immunodeficiency virus infection, opportunistic infections and neoplasms, alcohol abuse, and use of illicit drugs, which can also affect pancreatic amylase levels were not considered in these studies. In our study, we collected clinical data from newly diagnosed PLWH who had not received antiretroviral therapy, and examined the association between serum amylase levels and CD4 cell counts. Between November 2018 and September 2021, a total of 344 newly diagnosed PLWH and 344 healthy controls were recruited at Ningbo Yinzhou No 2 Hospital. Serum amylase levels, CD4 cell counts and other clinical features were measured. Relationships between serum amylase levels and clinical parameters were evaluated using correlation analysis. Multiple linear regression analyses were performed to identify the independent risk factors. Newly diagnosed PLWH had lower CD4 cell counts and higher serum amylase levels than healthy controls (P < .05). Serum amylase levels were negatively correlated with CD4 cell counts (r = −0.506, P < .001). In multiple linear regression analyses, CD4 cell counts (β = −0.327, 95% confidence interval = −0.051–−0.022, P < .001) were independently associated with serum amylase levels. CD4 cell counts were independently associated with serum amylase levels in newly diagnosed PLWH. Thus, close monitoring of serum amylase may be significant in preventing opportunistic infections of PLWH, since low CD4 cell counts are associated with an increased risk of opportunistic infections.
Metformin-associated severe lactic acidosis combined with multi-organ insufficiency induced by infection with Aeromonas veronii: A case report
Authors: Xia Yu , Zhu Xiaofeng , Wu Changxue
Published: January 2023

Rationale:

Lactic acidosis is a disease in which lactic acid accumulates in the blood and causes acidosis in the patient. The criteria for diagnosis are a lactate level of >2 mmol/L in the blood and a blood pH of <7.2.

Patient concerns:

A 72-year-old Asian female with a history of diabetes for 20+ years was admitted to the hospital with the chief complaint of “dry mouth, polydipsia for 20+ years, loss of appetite for 5+ days, vomiting for 1-day.” She was admitted with a blood gas pH of 6.795, and a lactate level of >30 mmol/L.

Diagnoses:

Type 2 diabetes mellitus with lactic acidosis, ketoacidosis, chronic renal insufficiency, hypertensive disease, and coronary arteriosclerotic heart disease.

Interventions:

She was treated with symptomatic rehydration and ketone reduction immediately, but then became unconscious and was admitted to the intensive care unit, where she was administered symptomatic support and continuous renal replacement therapy. As the blood culture showed Aeromonas veronii, she was administered a sensitive antibiotic in conjunction.

Outcomes:

However, after achieving a stable internal environment and good infection control, the patient’s family decided to discontinue treatment because of persistent heart failure with acute exacerbation of chronic renal insufficiency complicated by gastrointestinal bleeding.

Lessons:

Lactic acidosis has low incidence, poor prognosis, and high morbidity and mortality rates. Special attention should be paid to infection-induced acidosis, especially in patients with combined multi-organ insufficiency. Early diagnosis and active management can improve the patient prognosis.
High expression of KIF20A in bladder cancer as a potential prognostic target for poor survival of renal cell carcinoma
Authors: Liu Bin , Su Jianzhi , Fan Bo , Ni Xiaochen , Jin Tingting
Published: January 2023

Urinary system tumors are malignant tumors, including renal cancer and bladder cancer. however, molecular target of them remains unclear. GSE14762 and GSE53757 were downloaded from GEO database to screen differentially expressed genes (DEGs). Weighted gene co-expression network analysis was performed. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes were used for enrichment analysis. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed on whole genome, as formulated by gene set enrichment analysis. Survival analysis was also performed. Comparative toxicogenomics database was used to identify diseases most associated with hub genes. A total of 1517 DEGs were identified. DEGs were mainly enriched in cancer pathway, HIF-1 signaling pathway, organic acid metabolism, glyoxylate and dicarboxylate metabolism, and protein homodimerization activity. Ten hub genes (TPX2, ASPM, NUSAP1, RAD51AP1, CCNA2, TTK, PBK, MELK, DTL, kinesin family member 20A [KIF20A]) were obtained, which were up-regulated in tumor tissue. The expression of KIF20A was related with the overall survival of renal and bladder cancer. KIF20A was up-regulated in the tumor tissue, and might worsen the overall survival of bladder and kidney cancer. KIF20A could be a novel biomarker of bladder and kidney cancer.
A case report of hypertrophic olivine degeneration complicated with OSAHS exacerbation: Case report and retrospective analysis
Authors: Geng Minxia , Wang Lulu , Xing Jiahao , Li Shuang , Dong Lulu , Jiang Chao , Wang Tianjun
Published: January 2023

Rationale:

Hypertrophic subolivine degeneration (HOD) was destroyed by Guillain–Mollaret triangle (GMT) due to various injuries, resulting in anterograde cavity-like degeneration of the lower olive nucleus. In addition, the brain stem is related to the muscle coordination of the upper respiratory tract. Obstructive sleep apnea hypopnea syndrome may affect the respiratory center due to the injury of the brain stem. Brain stem hemorrhage damage GMT, resulting in transsynaptic neuronal degeneration. Clinical manifestations can be complex, and enhanced magnetic resonance imaging can be helpful in distinguishing them.

Patient concerns:

HOD is a self-limiting disease with no effective treatment and a long course of disease. Most patients can improve their symptoms after symptomatic treatment, and some patients can relieve their symptoms by themselves after 3 to 4 years.

Diagnosis interventions:

The limbs wobble involuntarily. His clinical symptoms and signs are consistent with HOD. Imaging with a clear primary lesion confirmed HOD. After treatment with antiepileptic drugs, the patient’s symptoms were relieved. Moreover, the patient had snoring and apnea, and respiratory sleep monitoring showed moderate obstructive sleep apnea hypopnea syndrome, which was treated with noninvasive ventilator.

Outcomes:

After treatment with antiepileptic drugs and noninvasive ventilator, the patient’s symptoms were significantly relieved.

Lessons:

HOD is a rare clinical disorder. Therefore, for similar patients, more attention should be paid to early diagnosis and treatment to avoid missed diagnosis, misdiagnosis and unnecessary intervention measures. The diagnosis can be confirmed by primary disease, clinical symptoms, and imaging based on GMT.
Severe Maternal Morbidity in Georgia, 2009–2020
Authors: Kramer Michael R. , Labgold Katie , Zertuche Adrienne D. , Runkle Jennifer D. , Bryan Michael , Freymann Gordon R. , Austin David , Adams E. Kathleen , Dunlop Anne L.
Published: January 2023

Background:

The increasing focus of population surveillance and research on maternal—and not only fetal and infant—health outcomes is long overdue. The United States maternal mortality rate is higher than any other high-income country, and Georgia is among the highest rates in the country. Severe maternal morbidity (SMM) is conceived of as a “near miss” for maternal mortality, is 50 times more common than maternal death, and efforts to systematically monitor SMM rates in populations have increased in recent years. Much of the current population-based research on SMM has occurred in coastal states or large cities, despite substantial geographical variation with higher maternal and infant health burdens in the Southeast and rural regions.

Methods:

This population-based study uses hospital discharge records linked to vital statistics to describe the epidemiology of SMM in Georgia between 2009 and 2020.

Results:

Georgia had a higher SMM rate than the United States overall (189.2 vs. 144 per 10,000 deliveries in Georgia in 2014, the most recent year with US estimates). SMM was higher among racially minoritized pregnant persons and those at the extremes of age, of lower socioeconomic status, and with comorbid chronic conditions. SMM rates were 5 to 6 times greater for pregnant people delivering infants <1500 grams or <32 weeks’ gestation as compared with those delivering normal weight or term infants. Since 2015, SMM has increased in Georgia.

Conclusion:

SMM represents a collection of life-threatening emergencies that are unevenly distributed in the population and require increased attention. This descriptive analysis provides initial guidance for programmatic interventions intending to reduce the burden of SMM and, subsequently, maternal mortality in the US South.
Collaborative Therapist-Patient Decision Making: A Power-Based Exercise Program for an Adolescent With CMT1A
Authors: Hedgecock James B. , Kelley Carolyn , Jensen Allison , Rapport Mary Jane
Published: January 2023

Purpose:

The purpose of this case report is to describe an episode of care for an adolescent with Charcot Marie Tooth disease (CMT) using a power-based progressive resistance exercise (PRE) and balance program to improve performance of participant-defined goals with added description through the voice of the patient as “participant lived experience.”

Summary of Key Points:

Participant discussion demonstrates improvement of functional performance for an adolescent with CMT subtype 1A (CMT1A), a progressive neuromuscular disorder. Function and participation-specific movement observation, clinical evaluation, and resistance training fostered appropriate program design and intervention dosing.

Conclusions and Recommendations for Clinical Practice:

A power-based progressive resistance exercise and balance program with design based on participant-defined goals was feasible, well tolerated, and successful for an adolescent with CMT1A. Inclusion of viewpoints of the “lived experience” provides deeper insight into patient perspective and clinical outcomes. Outcomes may improve when intervention is specifically dosed to participant goals and individual muscle performance requirements for targeted tasks.
Opportunities for Participation: A Mapping Review of Inclusive Physical Activity for Youth With Disabilities
Authors: Sawade Samantha
Published: January 2023

Introduction:

The purpose of this review is to map the literature regarding group-based inclusive and adapted physical activity opportunities for youth with disabilities, and to identify gaps in that literature.

Methods:

A comprehensive search was completed across 5 electronic databases. Inclusion criteria were for any study type with youth ages 3 to 21 years who participated in any adapted group-based physical activity program, or their caregivers.

Results:

A total of 30 studies were included from 13 countries, consisting of more than 15 types of physical activity. Levels of evidence ranged from 2b to 4 as per the Oxford Centre for Evidence-Based Medicine Levels of Evidence system.

Conclusions:

A small but growing body of evidence exists regarding group-based inclusive and adapted physical activity. A dearth of evidence exists for rurally residing programs and programs that include children with severe disabilities.
Informing the Physical Therapy Management of Congenital Muscular Torticollis Clinical Practice Guideline: A Systematic Review
Authors: Castilla Adrianna , Gonzalez Mariah , Kysh Lynn , Sargent Barbara
Published: January 2023

Purpose:

To systematically review current evidence on the physical therapy assessment, intervention, and prognosis of congenital muscular torticollis (CMT) to inform the update to the 2018 CMT Clinical Practice Guideline (CPG).

Methods:

Six databases were searched for studies that informed assessment, intervention, and prognosis for physical therapy management of infants with CMT.

Results:

Fifteen studies were included. Four studies investigated the psychometric properties of new and established assessments. Six studies informed the feasibility and efficacy of first-choice and supplemental interventions including traditional Chinese medicine and neural and visceral manipulation. One qualitative study found that parents of infants with mild and severe CMT had different concerns. Five studies informed prognosis, including factors associated with treatment duration, clinical outcomes, and use of supplemental interventions.

Conclusion:

Newer evidence reaffirms 5 of 17 recommendations of the 2018 CMT CPG and could increase the recommendation strength to strong for neck passive range of motion.
The Role of 68Ga-FAPI PET/CT in Detection of Metastatic Lobular Breast Cancer
Authors: Eshet Yael , Tau Noam , Apter Sara , Nissan Noam , Levanon Keren , Bernstein-Molho Rinat , Globus Ofer , Itay Amit , Shapira Tal , Oedegaard Cecilie , Gorfine Malka , Eifer Michal , Davidson Tima , Gal-Yam Einav , Domachevsky Liran
Published: January 2023

Purpose

Invasive lobular breast cancer (ILC) may be hard to detect using conventional imaging modalities and usually shows less avidity to 18F-FDG PET/CT. 68Ga–fibroblast activation protein inhibitor (FAPI) PET/CT has shown promising results in detecting non–18F-FDG–avid cancers. We aimed to assess the feasibility of detecting metastatic disease in patients with non–18F-FDG–avid ILC.

Methods

This prospective study included patients with metastatic ILC, infiltrative to soft tissues, which was not 18F-FDG avid. The patients underwent 68Ga-FAPI PET/CT for evaluation, which was correlated with the fully diagnostic CT performed at the same time.

Results

Seven women (aged 57 ± 10 years) were included. Among the 30 organs and structures found to be involved by tumor, the number of findings observed by FAPI PET/CT was significantly higher than that observed by CT alone (P = 0.022), especially in infiltrative soft tissue and serosal locations.

Conclusions

This small pilot trial suggests a role for 68Ga-FAPI PET/CT in ILC, which needs to be confirmed by subsequent trials.
Diagnostic value of plasma microbial cell-free DNA sequencing in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis
Authors: Degner Nicholas , Vissichelli Nicole C. , Berman David M. , Smollin Matt , Morales Megan K.
Published: January 2023

Hematopoietic stem cell transplant (HSCT) recipients are at increased risk for a wide spectrum of infections, including opportunistic infections with atypical presentations. Diagnosis can be challenging and often requires extensive testing and invasive procedures. Sequencing of plasma microbial cell-free DNA (mcfDNA) allows non-invasive untargeted detections of human pathogens, making this modality appealing for this patient population.

The purpose of this study was to perform a meta-analysis to evaluate the diagnostic value of sequencing of plasma mcfDNA for infections in HSCT recipients. We searched for relevant articles in BASE, PubMed, andClinicalTrials.govfrom January 1996 to November 2022. Studies were eligible for inclusion if they assessed the diagnostic performance of sequencing of plasma mcfDNA and included HSCT recipients with sufficient data to assign plasma mcfDNA test results as true positive, true negative, false positive, or false negative, which were used to calculate diagnostic test accuracy.

A total of 6 studies and 69 patients were included. All included studies were published in 2019 or later and were conducted in the United States. Three studies were exclusively pediatric, two exclusively adult, and one a mixture of both adult and pediatric patients. The pooled sensitivity was 0.90 (95% CI 0.71-0.97) and the pooled specificity was 0.75 (0.49-0.90).

The high pooled diagnostic odds ratio suggests that sequencing of plasma mcfDNA may have a unique diagnostic role in HSCT recipients. Its high sensitivity and capability to detect a broad array of pathogens makes it a promising adjunct to traditional diagnostic testing.
Investigating lesion location in relation to cerebellar mutism following pediatric tumor resection
Authors: Skye Jax , Bruss Joel , Toescu Sebastian , Aquilina Kristian , Lola Gino Bardi , Boes Aaron D.
Published: January 2023

Background and Objectives

Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar outflow pathway is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort.

Methods

We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated ‘lesion-symptom map’ of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/).

Results

We found supporting evidence for both hypotheses. Compared with CMS-patients, CMS+ patients (n=10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen’s d=.73, p=.05), and the CMS lesion-symptom map (Cohen’s d=1.1, p=.004).

Discussion

These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.
Pre-analytical variables influence zinc measurement in blood samples
Authors: Killilea David W. , Schultz Kathleen
Published: January 2023

Zinc deficiency continues to be a major concern for global public health. The zinc status of a target population is typically estimated by measuring circulating zinc levels, but the sampling procedures are not standardized and thus may result in analytical discrepancies. To examine this, we designed a study that controlled most of the technical parameters in order to focus on five pre-analytical variables reported to influence the measurement of zinc in blood samples, including (1) blood draw site (capillary or venous), (2) blood sample matrix (plasma or serum), (3) blood collection tube manufacturer (Becton, Dickinson and Company or Sarstedt AG & Co), (4) blood processing time (0, 4, or 24 hours), and (5) blood holding temperatures (4°C, 20°C, or 37°C). A diverse cohort of 60 healthy adults were recruited to provide sequential capillary and venous blood samples, which were carefully processed under a single chain of custody and measured for zinc content using inductively coupled plasma optical emission spectrometry. When comparing blood draw sites, the mean zinc content of capillary samples was 0.051 mg/L (8%) higher than venous blood from the same donors. When comparing blood sample matrices, the mean zinc content of serum samples was 0.034 mg/L (5%) higher than plasma samples from the same donors. When comparing blood collection tube manufacturer, the mean zinc content from venous blood samples did not differ between venders, but the mean zinc content from BD capillary plasma was 0.036 mg/L (6%) higher than Sarstedt capillary plasma from the same donors. When comparing processing times, the mean zinc content of plasma and serum samples was 5-12% higher in samples processed 4-24 hour after collection. When comparing holding temperatures, the mean zinc content of plasma and serum samples was 0.5-7% higher in samples temporarily held at 20°C or 37°C after collection. Thus even with the same donors and blood draws, significant differences in zinc content were observed with different draw sites, tube types, and processing procedures, demonstrating that key pre-analytic variables can have an impact on zinc measurement, and subsequent classification of zinc status. Minimizing these pre-analytical variables is important for generating best practice guidelines for assessment of zinc status.
spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content
Authors: De Jonghe Joachim , Kaminski Tomasz S. , Morse David B. , Tabaka Marcin , Ellermann Anna L. , Kohler Timo N. , Amadei Gianluca , Handford Charlotte , Findlay Gregory M. , Zernicka-Goetz Magdalena , Teichmann Sarah A. , Hollfelder Florian
Published: January 2023

Droplet microfluidic methods have massively increased the throughput of single-cell sequencing campaigns. The benefit of scale-up is, however, accompanied by increased background noise when processing challenging samples and the overall RNA capture efficiency is lower. These drawbacks stem from the lack of strategies to enrich for high-quality material or specific cell types at the moment of cell encapsulation and the absence of implementable multi-step enzymatic processes that increase capture. Here we alleviate both bottlenecks using fluorescence-activated droplet sorting to enrich for droplets that contain single viable cells, intact nuclei, fixed cells or target cell types and use reagent addition to droplets by picoinjection to perform multi-step lysis and reverse transcription. Our methodology increases gene detection rates fivefold, while reducing background noise by up to half. We harness these unique properties to deliver a high-quality molecular atlas of mouse brain development, despite starting with highly damaged input material, and provide an atlas of nascent RNA transcription during mouse organogenesis. Our method is broadly applicable to other droplet-based workflows to deliver sensitive and accurate single-cell profiling at a reduced cost.
Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases
Authors: Hata Kentaro , Yanagihara Toyoshi , Matsubara Keisuke , Kunimura Kazufumi , Suzuki Kunihiro , Tsubouchi Kazuya , Eto Daisuke , Ando Hiroyuki , Uehara Maki , Ikegame Satoshi , Baba Yoshihiro , Fukui Yoshinori , Okamoto Isamu
Published: January 2023

Immune cells have been implicated in interstitial lung diseases (ILDs), although their phenotypes and effector mechanisms remain poorly understood. To better understand these cells, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), connective-tissue disease (CTD)-related ILD, and sarcoidosis, using two panels including 64 markers. Among myeloid cells, we observed the expansion of CD14+CD36hiCD84himonocyte populations in IPF. These CD14+CD36hiCD84hisubsets were also increased in ILDs with a progressive phenotype, particularly in a case of acute exacerbation (AEx) of IPF. Analysis of B cells revealed the presence of cells at various stages of differentiation in BALF, with a higher percentage of IgG memory B cells in CTD-ILDs and a trend toward more FCRL5+B cells. These FCRL5+B cells were also present in the patient with AEx-IPF and sarcoidosis with advanced lung lesions. Among T cells, we found increased levels of IL-2R+TIGIT+LAG3+CD4+T cells in IPF, increased levels of CXCR3+CD226+CD4+T cells in sarcoidosis, and increased levels of PD1+TIGIT+CD57+CD8+T cells in CTD-ILDs. Together, these findings underscore the diverse immunopathogenesis of ILDs.
Evaluation of the morphological and biological functions of vascularized microphysiological systems with supervised machine learning
Authors: Tronolone James J. , Mathur Tanmay , Chaftari Christopher P. , Jain Abhishek
Published: January 2023

Vascularized microphysiological systems and organoids are contemporary preclinical experimental platforms representing human tissue or organ function in health and disease. While vascularization is emerging as a necessary physiological organ-level feature required in most such systems, there is no standard tool or morphological metric to measure the performance or biological function of vascularized networks within these models. Further, the commonly reported morphological metrics may not correlate to the network’s biological function – oxygen transport. Here, a large library of vascular network images was analyzed by the measure of each sample’s morphology and oxygen transport potential. The oxygen transport quantification is computationally expensive and user-dependent, so machine learning techniques were examined to generate regression models relating morphology to function. Principal component and factor analyses were applied to reduce dimensionality of the multivariate dataset, followed by multiple linear regression and tree-based regression analyses. These examinations reveal that while several morphological data relate poorly to the biological function, some machine learning models possess a relatively improved, but still moderate predictive potential. Overall, random forest regression model correlates to the biological function of vascular networks with relatively higher accuracy than other regression models.
SSI: A Statistical Sensitivity Index for Chemical Reaction Networks in cancer
Authors: Biddau Giorgia , Caviglia Giacomo , Piana Michele , Sommariva Sara
Published: January 2023

Summary

At the cellular level, cancer is triggered by mutations of the proteins involved in signalling networks made of hundreds of reacting species. The corresponding mathematical model consists of a large system of non-linear Ordinary Differential Equations for the unknown proteins concentrations depending on a consistently large number of kinetic parameters and initial concentrations. For this model, the present paper considers the problem of assessing the impact of each parameter and initial concentration on the system’s output. More specifically, we introduced a statistical sensitivity index whose values can be easily computed by means of principal component analysis, and which leads to the partition of the parameters’ and initial concentrations’ sets into sensible and non-sensible families. This approach allows the identification of those kinetic parameters and initial concentrations that mostly impact the mutation-driven modification of the proteomic profile at equilibrium, and of those pathways in the network that are mostly affected by the presence of mutations in the cancer cell.
Scalable Nanopore sequencing of human genomes provides a comprehensive view of haplotype-resolved variation and methylation
Authors: Kolmogorov Mikhail , Billingsley Kimberley J. , Mastoras Mira , Meredith Melissa , Monlong Jean , Lorig-Roach Ryan , Asri Mobin , Jerez Pilar Alvarez , Malik Laksh , Dewan Ramita , Reed Xylena , Genner Rylee M. , Daida Kensuke , Behera Sairam , Shafin Kishwar , Pesout Trevor , Prabakaran Jeshuwin , Carnevali Paolo ,   North American Brain Expression Consortium (NABEC), Yang Jianzhi , Rhie Arang , Scholz Sonja W. , Traynor Bryan J. , Miga Karen H. , Jain Miten , Timp Winston , Phillippy Adam M. , Chaisson Mark , Sedlazeck Fritz J. , Blauwendraat Cornelis , Paten Benedict
Published: January 2023

Long-read sequencing technologies substantially overcome the limitations of short-reads but to date have not been considered as feasible replacement at scale due to a combination of being too expensive, not scalable enough, or too error-prone. Here, we develop an efficient and scalable wet lab and computational protocol for Oxford Nanopore Technologies (ONT) long-read sequencing that seeks to provide a genuine alternative to short-reads for large-scale genomics projects. We applied our protocol to cell lines and brain tissue samples as part of a pilot project for the NIH Center for Alzheimer’s and Related Dementias (CARD). Using a single PromethION flow cell, we can detect SNPs with F1-score better than Illumina short-read sequencing. Small indel calling remains difficult within homopolymers and tandem repeats, but is comparable to Illumina calls elsewhere. Further, we can discover structural variants with F1-score comparable to state-of-the-art methods involving Pacific Biosciences HiFi sequencing and trio information (but at a lower cost and greater throughput). Using ONT-based phasing, we can then combine and phase small and structural variants at megabase scales. Our protocol also produces highly accurate, haplotype-specific methylation calls. Overall, this makes large-scale long-read sequencing projects feasible; the protocol is currently being used to sequence thousands of brain-based genomes as a part of the NIH CARD initiative. We provide the protocol and software as open-source integrated pipelines for generating phased variant calls and assemblies.
Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain
Authors: Pessa Joel E. , Hoxworth Ronald M.
Published: January 2023

How cerebrospinal fluid (CSF) drains from the human brain is of paramount importance to cerebral health and physiology. Obstructed CSF drainage may result in increased intracranial pressure and a predictable cascade of events including an enlarged subarachnoid space, dilated cerebral ventricles and ultimately cell death. The current and accepted model of CSF drainage in humans suggests CSF drains from the subarachnoid space into the sagittal sinus vein. Here we identify a new structure in the sagittal sinus of the human brain by anatomic cadaver dissection. TheCSF canalicular systemis the terminal CSF drainage of the human brain. It consists of paired channels on either side of the sagittal sinus vein that communicate directly with subarachnoid cerebrospinal fluid via virchow robin (perivascular) spaces. Fluorescent injection confirms that these channels are patent and that flow is independent of the venous system. Computer assisted tomography identified flow from the sagittal sinus to the cranial base. We verify our previous identification of CSF channels in the neck that travel from the cranial base to the subclavian vein. This information suggests a novel path for CSF drainage of the human brain and nerves that may represent the primary route for CSF recirculation. These findings have implications for basic anatomy, surgery, and neuroscience, and highlight the continued importance of gross anatomy to medical research and discovery.
Immunogenicity and seroefficacy of pneumococcal conjugate vaccines – a systematic review and network meta-analysis
Authors: Feng Shuo , McLellan Julie , Pidduck Nicola , Roberts Nia , Higgins Julian PT , Choi Yoon , Izu Alane , Jit Mark , Madhi Shabir A , Mulholland Kim , Pollard Andrew J , Temple Beth , Voysey Merryn
Published: January 2023

Background

Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organisation. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines.

Methods

In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline,clinicaltrials.govand trialsearch.who.int up to July 2022 (Protocol PROSPERO ID CRD42019124580). Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head- to-head randomised trials for young children, and provided at least one time point after the primary vaccination series and/or one-month after a booster dose. Individual participant level data were requested from publication authors and/or the relevant vaccine manufacturer; aggregate data were extracted if individual data were unavailable. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and relative risk (RR) of seroinfection. Seroinfection is defined as a rise in antibody between the primary vaccination series and the booster dose, as evidence of subclinical infection. We also estimated the relationship between the GMR one month after priming and the RR of seroinfection by the time of the booster dose.

Findings

In total 45 studies were eligible from 38 countries across six continents. 27 and 12 studies with data available were included in immunogenicity and seroefficacy analyses respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Two-fold higher antibody after primary vaccination was associated with 54% decrease in risk of seroinfection (RR 0.46, 95%CI 0.23-0.96).

Conclusion

Serotype-specific differences were found in immunogenicity and seroefficacy between PCV10 and PCV13. Higher immunogenicity of PCVs are associated with lower risk of subsequent infection. These findings could be further used to compare PCVs and optimise vaccination strategy.

Funding

This study is funded by the NIHR Health Technology Assessment programme (17/148/03).
Global biogeography of the smallest plankton across ocean depths
Authors: Junger Pedro C. , Sarmento Hugo , Giner Caterina. R. , Mestre Mireia , Sebastián Marta , Morán Xosé Anxelu G. , Arístegui Javier , Agustí Susana , Duarte Carlos M. , Acinas Silvia G. , Massana Ramon , Gasol Josep M. , Logares Ramiro
Published: January 2023

Tiny ocean plankton (picoplankton) are fundamental for the functioning of the biosphere, but the ecological mechanisms shaping their biogeography are partially understood. Comprehending whether these microorganisms are structured by niche vs. neutral processes is highly relevant in the context of global change. The ecological drivers structuring picoplankton communities differ between prokaryotes and minute eukaryotes (picoeukaryotes) in the global surface ocean: while prokaryotic communities are shaped by a balanced combination ofdispersal, selection, anddrift, picoeukaryotic communities are mainly shaped bydispersal limitation. Yet, whether or not the relative importance of these processes in structuring picoplankton varies as we dive into the deep ocean was unknown. Here we investigate the mechanisms structuring picoplanktonic communities inhabiting different ocean depths. We analyzed 451 samples from the tropical and subtropical global ocean and the Mediterranean Sea covering the epi- (0-200m), meso- (200- 1,000m), and bathypelagic (1,000-4,000m) depth zones. We found that selection decreased with depth possibly due to lower habitat heterogeneity. In turn, dispersal limitation increased with depth, possibly due to dispersal barriers such as water masses and bottom topography. Picoplankton β-diversity positively correlated with environmental heterogeneity and water mass variability in both the open-ocean and the Mediterranean Sea. However, this relationship tended to be weaker for picoeukaryotes than for prokaryotes. Community patterns were generally more pronounced in the Mediterranean Sea, probably because of its substantial cross-basin environmental heterogeneity and deep-water isolation. Altogether, we found that different combinations of ecological mechanisms shape the biogeography of the smallest members of the ocean microbiome across ocean depths.