bluuebunny/crossref_metadata_2025 huggingface dataset:
Balance Training Modulates Cortical Inhibition in Individuals with Parkinson’s Disease: A Randomized Controlled Trial
Authors: Liu Hsin-Hsuan , Wang Ray-Yau , Cheng Shih-Jung , Liao Kwong-Kum , Zhou Jun-Hong , Yang Yea-Ru
Published: August 2022

Background

Most individuals with Parkinson’s disease (PD) develop balance dysfunction. Previous studies showed that individuals with PD have abnormal corticomotor changes related to severity of motor symptoms and disease progression. Cortical disinhibition was observed in PD and this alteration can be an early sign of PD. Balance training seems to be an effective intervention to improve balance in individuals with PD. However, it is not much known about the effect of balance training on cortical neuroplasticity in PD population.

Objective

To investigate the effects of balance training on corticomotor excitability in individuals with PD.

Methods

Twenty-eight PD participants were recruited and randomly assigned to either the balance training (BT) or the control (CON) group. Both groups underwent 16 training sessions over 8 weeks. Outcome measures for corticomotor inhibition included the cortical silent period (CSP) and short-interval intracortical inhibition (SICI) on transcranial magnetic stimulation. Balance performance was measured using the Mini-Balance Evaluation Systems Test (Mini-BEST) and the Timed Up and Go (TUG) test.

Results

Participants in the BT group showed a significant increase in corticomotor inhibition (CSP: P = .028, SICI: P = .04) and a significant improvement in balance performance (Mini-BEST: P = .001, TUG: P = .04) after training. Compared to the CON group, the BT group showed a greater increase in corticomotor inhibition (CSP: P = .017, SICI: P = .046) and better improvement in balance (Mini-BEST: P = .046).

Conclusion

Balance training could modulate corticomotor inhibition in the primary motor cortex and improve balance performance in individuals with PD.
Aero-engine exhaust gas temperature prediction based on adaptive disturbance quantum-behaved particle swarm optimization
Authors: Zhou Wengang
Published: August 2022

Aircraft engine EGT (exhaust gas temperature) is uncertain. In order to reduce the EGT influence to the health of the engine, it is important to carry out the prediction. A novel EGT prediction method based on the combination method is proposed. Firstly, MIV (Mean Impact Value) was used to reduce the dimension of the input numbers. Second, the EGT was predicted by some single models such as BP (back propagation) neural network model, SVR (support vector regression) model, PLS (partial least square) model, GM(1,N) (multi-parameter input gray prediction model), MLR (multiple linear regression) model. Then absolute mean error was used to evaluate the predictive results of single models and the best predictive results of four single methods were selected to establish combination model with PSO (particle swarm optimization). Finally, the combination model was used in predicting the EGT of V2500 aero-engine. Experiment results show that the combination method is more reliable and suitable than the single models for aero-engine EGT prediction.
A Systematic Review of Black People Coping With Racism: Approaches, Analysis, and Empowerment
Authors: Jacob Grace , Faber Sonya C. , Faber Naomi , Bartlett Amy , Ouimet Allison J. , Williams Monnica T.
Published: August 2022

This article reviews the current research literature concerning Black people in Western societies to better understand how they regulate their emotions when coping with racism, which coping strategies they use, and which strategies are functional for well-being. A systematic review of the literature was conducted, and 26 studies were identified on the basis of a comprehensive search of multiple databases and reference sections of relevant articles. Studies were quantitative and qualitative, and all articles located were from the United States or Canada. Findings demonstrate that Black people tend to cope with racism through social support (friends, family, support groups), religion (prayer, church, spirituality), avoidance (attempting to avoid stressors), and problem-focused coping (confronting the situation directly). Findings suggest gender differences in coping strategies. We also explore the relationship between coping with physical versus emotional pain and contrast functional versus dysfunctional coping approaches, underscoring the importance of encouraging personal empowerment to promote psychological well-being. Findings may help inform mental-health interventions. Limitations include the high number of American-based samples and exclusion of other Black ethnic and national groups, which is an important area for further exploration.
Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function
Authors: Huynh Jasmine , Cho May Thet , Kim Edward Jae-Hoon , Ren Min , Ramji Zahra , Vogel Arndt
Published: August 2022

Background:

Lenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment.

Methods:

We retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8.

Results:

Patients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8–7.4] and 6.8 months (95% CI: 2.6–10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6–7.4) and 13.3 months (95% CI: 11.6–16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1–3.6) and 4.5 months (95% CI: 2.9–6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7–3.7) and 12.0 months (95% CI: 10.2–14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup).

Conclusion:

Results suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib.

Trial registration:

ClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266 .
MRI lesions in SpA: a comparison with noninflammatory back pain using propensity score adjustment method
Authors: Chung Ho Yin , Huang Jin Xian , Lee Kam Ho , Tsang Helen Hoi Lun , Lau Chak Sing , Chan Shirley Chiu Wai
Published: August 2022

Background:

Magnetic resonance imaging (MRI) is important in the management of axial spondyloarthritis (SpA). However, many MRI lesions are not exclusive to axial SpA. Further characterization of these lesions may lead to better clinical decisions.

Objective:

The objective of this study was to compare the frequency of individual spinal MRI lesions between axial SpA and noninflammatory back pain. The factors associated with individual lesions in participants with axial SpA were also determined.

Design:

This was a cross-sectional observational study.

Methods:

MRI lesions in 447 participants with axial SpA and 122 participants with noninflammatory back pain were compared using the propensity score adjustment method. Individual lesions included discovertebral lesions (DVL), Modic type 1 lesions, DVL without Modic type 1 lesions, facet joint lesions, costovertebral joint lesions, corner inflammatory lesions (CIL), and fatty corner lesions (FCL). The factors associated with the lesions were determined using regression analyses.

Results:

Among participants with axial SpA, 81.9% were HLA-B27-positive, 55.0% had radiographic axial SpA, and 60.5% had radiographic features of spinal damage (mSASSS >2). Almost half (48.6% in axial SpA versus 31.1% in noninflammatory back pain) had inflammatory lesions on spinal MRI. In propensity score matching with noninflammatory back pain, axial SpA had an increased occurrence of DVL without Modic type 1 lesion (OR = 3.43, p = 0.01), costovertebral lesion (OR = 11.89, p = 0.02), number of CIL ( B = 1.19, p < 0.001), and number of FCL ( B = 3.33, p < 0.001). Similar associations were found in the regression models in the radiographic axial SpA subgroup: DVL without Modic type 1 lesion (OR = 2.46, p = 0.001), costovertebral lesion (OR = 3.86, p < 0.001), number of CIL ( B = 1.13, p < 0.001), and FCL ( B = 2.29, p < 0.01).

Conclusion:

MRI lesions including DVL without Modic type 1, costovertebral joint lesions, CIL, and FCL were more specific in axial SpA.
The Important Role of TaohongSiwu Decoction in Gut Microbial Modulation in Response to High-Salt Diet-Induced Hypertensive Mice
Authors: Liu Tian-hao , Xie Ting , Bai Zhen-yu , Liang Qiu-er , Xie Peng-cheng , Xue Yu-zheng , Xiao Ya , Chen Li-guo
Published: August 2022

TaohongSiwu decoction (THSWD), a traditional Chinese recipe, has been widely used to treat hypertension since ancient times. However, the mechanisms of its action are still unclear. Herein, we aimed to explore the gut microbial activity of THSWD in high-salt diet-induced hypertensive mice. Eight percent high-salt (NaCl) diet was used to induce hypertension for 4 weeks in a mouse model. Meanwhile, THSWD was used to intervene in the high-salt diet-induced mice, and the efficacy was evaluated by different parameters. Here, we found that THSWD significantly restored blood pressure compared with the model group. Moreover, THSWD effectively protected endothelial function by significantly upregulating the level of nitric oxide (NO) and downregulating the level of endothelin-1 (ET-1), angiotensin I (AngI), and vascular endothelial growth factor (VEGF) in serum compared with the model group. Notably, THSWD significantly upregulated the relative abundance of Dubosiella and downregulated that of Cyanobium_PCC-6307 and DNF00809 at the genus level compared with the model group. The results of PCA and microbial distance calculation further exhibited that THSWD treatment resulted in significant regulation of the microbial community. Furthermore, compared with the model group, THSWD increased the level of vitamin k2 (VK2) in serum. These findings indicate that THSWD could protect blood pressure and endothelial function by regulating gut microbiota and promoting microbial metabolite VK2. These results show the important role of THSWD in regulating the gut microbiota in response to high-salt diet-induced mice.
Global safety monitoring of COVID-19 vaccines: how pharmacovigilance rose to the challenge
Authors: Rudolph Annette , Mitchell Joseph , Barrett Jim , Sköld Helena , Taavola Henric , Erlanson Nils , Melgarejo-González Carlos , Yue Qun-Ying
Published: August 2022

Pharmacovigilance (PV) came suddenly into the spotlight when several new vaccines, developed as a response to the COVID-19 pandemic, received emergency authorisation and were rolled out on a large scale in late 2020. The vaccines underwent stringent clinical trials and evaluation from regulatory authorities, but with the use of novel technology and an anticipated rapid and vast deployment of the vaccines, the importance of a well-functioning international post marketing safety surveillance system was stressed. International PV stakeholders were faced with several challenges due to the extent of the global vaccination campaign. The unprecedented volume of reports of suspected adverse events following immunization has led to the development and use of new tools. Furthermore, the collaboration between various PV stakeholders was encouraged and strengthened. PV rose to the challenges posed by the currently ongoing global COVID-19 vaccination campaign and successful adaptations were made in a short period of time. However, the pandemic has not ended yet, the vaccination campaign is far from being completed, and further challenges are anticipated. Advances made during the pandemic will be important to strengthen PV in future and ensure to advance medicines’ safety together.

Plain Language Summary

Global safety monitoring of the COVID-19 vaccines: challenges, preparations, and outlooks Pharmacovigilance (PV) is the umbrella term for all sciences and activities relating to the detection, assessment, understanding, and prevention of adverse effects relating to medicines or vaccines. PV came into the spotlight when several new vaccines were authorised and rolled out as a response to the COVID-19 pandemic. The anticipated extent of the global vaccine rollout stressed the importance of a well-functioning safety surveillance system and international collaborations between patients, health care workers, vaccine producers, regulatory authorities, and PV centres. The identification and communication of potential safety concerns showed that adaptations to PV processes made in a short period of time as well as international collaborations were successful. However, it is important to learn from experiences made so far and to make sure the positive advances are maintained in the future to advance medicines’ safety together.
The implications and management of complex biliary injuries at a tertiary hepatobiliary specialty center
Authors: Kakati Rasha T , Othman Mohamad , Kharroubi Hussein , Ataya Karim , Nassar Hussein , Hafez Bassel , Faraj Walid , Khalife Mohamad Jawad
Published: August 2022

Injuries of the biliary tract and complex injuries involving vascular and parenchymal tissue can be detrimental despite the improved use of laparoscopy. Complex biliary injuries are variable depending on the type of injury as well as patient and surgeon factors. We present four cases of complex biliary injuries at our tertiary referral center with hepatobiliary expertise: biliary stenosis with obstruction, double duct system anatomy, combined right hepatic arterial transection and biliary duct injury, and a complete pedicle injury. Early identification and specialized repair of complex biliary injuries is essential to minimize patient morbidity. Notably, consulting a specialist intraoperatively in case of difficult dissection and visualization or a suspected injury and considering bail-out strategies such as a subtotal cholecystectomy or conversion are safe approaches to minimize complex biliary injuries. Earlier recognition and repair of complex biliary injuries improves outcomes when immediate intraoperative repair can be performed rather than delayed postoperatively.
Characteristics of patients with xanthogranulomatous pyelonephritis undergoing nephrectomy: Identifying ways to optimise outcomes
Authors: Pfeifer Jacob , Wang Luke , Fu David , Stormont Gavin , Hill Brett , LaGrange Chad
Published: August 2022

Objective:

This study is conducted to investigate characteristics of patients with xanthogranulomatous pyelonephritis (XGP) who undergo nephrectomy and to identify ways to optimise outcomes for these patients.

Materials and methods:

1587 patients were queried from our institutional electronic medical records. 12 patients who underwent nephrectomy with preoperative diagnoses of XGP in the operative note were identified. Associations were analysed with Kendall’s τb. p < 0.05 was statistically significant.

Results:

All patients were hemodynamically stable on day of surgery. Two patients died on postoperative days 1 and 3 from septic shock. Both had surgery during inpatient admission rather than electively, received relatively short duration of preoperative antibiotics (8 and 10 days), and both were on hemodialysis preoperatively. There was possible association between decreased glomerular filtration rate (τb = −0.550, p = 0.032) and death postoperatively. Among patients who lived, there was no significant association between duration of antibiotic therapy after intervention and duration of postoperative hospitalisation.

Conclusion:

These findings could suggest a possible association between declining renal function and mortality in our case series; and performing nephrectomy electively after a longer course of antibiotics may be associated with improved outcomes compared to nephrectomy performed during hospitalisation with a shorter course of antibiotics.

Level of evidence:

Level 4
Exploring creative pedagogies for research methods: Reflections from a workshop series
Authors: Mainsah Henry
Published: August 2022

This article describes a series of experimental method workshops that invite participants to enact speculative, craftful, multisensory and performative research techniques. The workshops have taken place across different European university venues with graduate students in a variety of disciplines such as digital humanities, sociology, design, media and art. Drawing on these experiences, the article argues that these workshops serve as an avenue for widening the repertoire of pedagogies for interdisciplinary qualitative inquiry through engagement with material, experiential and embodied ways of knowing. The article articulates the need to widen the repertoire of pedagogies for interdisciplinary qualitative inquiry.
A Novel Clinical Tool to Predict Cancer-specific Survival in Postoperative Patients With Primary Spinal and Pelvic Sarcomas: A Large Population-Based Retrospective Cohort Study
Authors: Huang Chao , Huang Zhangheng , Ding Zichuan , Zhou Zongke
Published: August 2022

Study Design

Retrospective cohort study.

Objective

Primary osseous sarcomas originating from the spine and pelvis are rare and usually portend inferior prognoses. Currently, the standard treatment for spinal and pelvic sarcomas is surgical resection, but the poor prognosis limits the benefits to postoperative patients. This study aims to identify the independent prognostic factors of cancer-specific survival (CSS) in postoperative patients with primary spinal and pelvic sarcomas and construct a nomogram for predicting these patients’ 3-, 5-, and 10-year CSS probability.

Methods

A total of 452 patients were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. They were divided into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to identify these patients’ CSS-related independent prognostic factors. Then, those factors were used to construct a prognostic nomogram for predicting the 3-, 5-, and 10-year CSS probability, whose predictive performance and clinical value were verified by the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Finally, a mortality risk stratification system was constructed.

Results

Sex, histological type, tumor stage, and tumor grade were identified as CSS-related independent prognostic factors. A nomogram with high predictive performance and good clinical value to predict the 3-, 5-, and 10-year CSS probability was constructed, on which a mortality risk stratification system was constructed based to divide these patients into 3 mortality risk subgroups effectively.

Conclusions

This study constructed and validated a clinical nomogram to predict CSS in postoperative patients with primary spinal and pelvic sarcomas. It could assist clinicians in classifying these patients into different mortality risk subgroups and realize sarcoma-specific management.
The Racial Contract: Challenging White Supremacy in Sociological Theories and Providing a Global Theory for Race
Authors: Selod Saher
Published: August 2022

In The Racial Contract Charles Mills argues that the social contract is an epistemological theory that is steeped in white supremacy. I do two things in this essay. First, I use my personal experiences in graduate school to show how gate keeping in academia is still perpetuated via promoting scholarship that was created for white experiences by white scholars. I use Mills’ work to highlight how scholars of color who study communities of color are still struggling with theoretical frameworks that do not adequately explain or represent the lived experiences of the populations they are studying. In the second portion of the essay, I call on race scholars in the United States to think more broadly about colonialism and global racism, something that Charles Mills advocates for in The Racial Contract.
Neuropsychological Performance and Engagement in Estate Planning and Advance Care Planning Preparation of Patients With Neurocognitive Disorders and Healthy Older Adults: Is the Situation Alarming or Reassuring in Greece?
Authors: Giannouli Vaitsa , Tsolaki Magda
Published: August 2022

Background/Objective:

This study examined for the first time in Greece, the estate planning and advance care planning (ACP) of healthy older adults and older patients diagnosed with different types of neurocognitive disorders for the presence of a valid will, a durable power of attorney for healthcare, and a living will, while the associations between general cognition, education, depression, actual financial capacity, and demographic and socioeconomic characteristics were examined.

Methods:

A total of 543 participants were examined with neuropsychological tests including Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). Along with the neuropsychological examination, all participants responded to relevant ACP questions.

Results:

Surprisingly, the majority of the participants regardless of their diagnostic group did not have a valid will, had not assigned a durable power of attorney for healthcare, and had not a written living will. Logistic regression revealed that biological sex, age, education, marital status, diagnostic group, MMSE, GDS, and actual financial capacity as measured with LCPLTAS did not predict the existence of a valid will, durable power of attorney, and written living will.

Conclusions:

A diagnosis of AD is not associated with more engagement in ACP as supported by research in USA. Concerns are raised about possible exploitation and abuse of older patients.
“The Long Wait for Homecoming”: Looking at the Lives of Oil Field Wives in COVID-19 Times
Authors: Chatterjee Anindita
Published: August 2022

The migration of Indians to Gulf countries can be traced back to the early twentieth century. With the discovery of oil in the region, Indian laborers began to migrate for a better livelihood, which also served as a valuable source of income for the country. Oil field workers who have migrated from India to the Gulf region are employed in oil rigs located in remote desert areas. They include both skilled as well as unskilled laborers and are employed in high-risk field-based jobs wherein family is not allowed. They work as international commuters and return home on a rotational basis at regular intervals. They constitute transnational families wherein most rely on telecommunication to connect with their family members in India and fulfill their social obligations. The economic, political, and sociocultural impact of migration has been studied by social scientists in substantial detail from the perspective of homeland as well as host land, but not much has been discussed about the experience of wives/spouses of oil field workers who are left behind at home even though their population is fairly large in India. Available data on the social and psychological impact of international migration suggest that such migration histories have both positive and negative impacts on transnational families. The COVID-19 pandemic, which affected the global scenario, did not spare them either. This article is a part of a meso-level study wherein a group of women residing in different parts of India was interviewed regarding their experience as wives of oil field workers in Gulf countries. Their husbands could not return home due to travel bans imposed by the Middle Eastern countries owing to the pandemic. This article attempts to look at significant issues pertaining to family and international migration to Gulf countries in the COVID times.
Utility of No-Charge Panel Genetic Testing for Inherited Retinal Diseases in a Real-World Clinical Setting
Authors: McClard Cynthia K. , Pollalis Dimitrios , Jamshidi Farzad , Kingsley Ronald , Lee Sun Young
Published: August 2022

Purpose:

To show the utility of genetic testing in inherited retinal disease (IRD) patients.

Methods:

This retrospective cohort study was performed at a single academic center and comprised 59 patients clinically diagnosed with IRD who had testing via the Invitae IRD Panel (Invitae Corp). Samples were collected from August 2019 to April 2021. The rates of genetic diagnosis and disease-category specific results (ie, positive, undetermined, negative) were assessed.

Results:

Testing results were returned a mean of 20 days (range, 14-28 days) after submission. Of the samples, 50.8% (30/59) had a diagnostic yield. By disease category, the yield was 46.4% (13/28) nonsyndromic retinitis pigmentosa (RP), 50.0% (4/8) syndromic RP, 46.2% (6/13) macular dystrophies, 75.0% (3/4) cone or cone-rod dystrophies, and 80.0% (4/5) other retinopathies; there were no cases of rod dystrophies. The results were undetermined in 47.5% of patients (28/59) because of identification of only 1 recessive mutation (5.1%; 3/59), 1 recessive mutation and at least 1 variant of uncertain significance (VUS) (13.6%; 8/59), or VUS only (28.8%; 17/59). One patient (1.7%) received negative testing results with no mutations or VUS identified.

Conclusions:

Open-access, no-charge panel testing offers a reasonable diagnostic yield. Accurate clinical diagnosis of IRD before testing and acknowledgment of the limitations of panel testing are critical. The results add to the current estimates of the value of genetic testing for retina specialists in the management of IRD.
Breast Metaplastic Carcinoma With Osteosarcomatous Differentiation: A Case Report and literature Review
Authors: Yang Xue , Chen Ling , Shen Yan
Published: August 2022

Metaplastic breast carcinoma (MBCs) is a rare heterogeneous group of malignancies. Herein, we report a case of metaplastic breast carcinoma, which had 2 components. One of them was typical invasive ductal carcinoma (IDC), the other one was presenting as osteosarcoma with lots of immature trabeculae. The results of immunohistochemistry showed different presentations between them. The majority of MBCs show triple-negativity for ER, PR, and HER-2 and are thus associated with poor prognosis. Our report shows that, it is necessary to describe the proportion of the components and the presentations of immunohistochemistry in the diagnosis, which will be important to develop specific and effective therapies.
Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease
Authors: Ruiz Maria A. , Shah Binal N. , Ren Guohui , Hussain Faiz , Njoku Franklin , Machado Roberto F. , Gordeuk Victor R. , Saraf Santosh L.
Published: August 2022

Haptoglobin (HP) is an acute-phase protein and the main scavenger of cell-free hemoglobin. When HP is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of patients with SCD, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode or acute chest syndrome. With a median follow-up of 6.8 years, acute chest syndrome occurred in 42% (n = 163) and multiorgan failure in 14% (n = 53) of 391 patients with SCD with a minimum follow-up of 6 months. The HP 1 allele was independently associated with lower risk of developing multiorgan failure during acute chest syndrome (additive model hazard ratio, 0.5; P < .001). Future studies assessing the regulation of HP concentrations and ability to bind cell-free hemoglobin according to the HP genotype may help to identify patients with SCD at high risk for multiorgan failure and to guide interventions, such as rapid initiation of exchange transfusion or HP replacement therapy.
GFAP and NfL increase during neurotoxicity from high baseline levels in pediatric CD19-CAR T-cell patients
Authors: Gust Juliane , Rawlings-Rhea Stephanie D. , Wilson Ashley L. , Tulberg Niklas M. , Sherman Amber L. , Seidel Kristy D. , Wu Qian “Vicky” , Park Julie R. , Gardner Rebecca A. , Annesley Colleen E.
Published: August 2022

There is a need for biomarkers to predict and measure the severity of immune effector cell–associated neurotoxicity syndrome (ICANS). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are well-validated biomarkers of astroglial and neuronal injury, respectively. We hypothesized that pretreatment GFAP and NfL levels can predict the risk of subsequent ICANS and that increases in GFAP and NfL levels during treatment reflect ICANS severity. We measured cerebrospinal fluid GFAP (cGFAP) and NfL (cNfL) along with serum NfL (sNfL) levels at pretreatment and day 7 to 10 after chimeric antigen receptor (CAR) T-cell infusion in 3 pediatric cohorts treated with CD19- or CD19/CD22-directed CAR T cells. cGFAP and cNfL levels increased during grade ≥1 ICANS in patients treated with CD19-directed CAR T cells but not in those who received CD19/CD22-directed CAR T cells. The sNfL levels did not increase during ICANS. Prelymphodepletion cGFAP, cNfL, and sNfL levels were not predictive of subsequent ICANS. Elevated baseline cGFAP levels were associated with a history of transplantation. Patients with prior central nervous system (CNS) radiation had higher cNfL levels, and elevated baseline sNfL levels were associated with a history of peripheral neuropathy. Thus, cGFAP and cNfL may be useful biomarkers for measuring the severity of CNS injury during ICANS in children. Elevated baseline levels of cGFAP, cNfL, and sNfL likely reflect the cumulative injury to the central and peripheral nervous systems from prior treatment. However, levels of any of the 3 biomarkers before CAR T-cell infusion did not predict the risk of ICANS.
Vascular surgery patients with elevated neutrophil-to-lymphocyte ratios have downregulated neutrophil complement RNA expression
Authors: Chan Ernest R. , Lee Jasmine , Meyerson Howard , Merkulova Alona , Smith Susan , Lin Feng , Cho Jae S. , Schmaier Alvin H.
Published: August 2022

Elevated neutrophil-to-lymphocyte ratio (NLR) in patients who undergo elective vascular surgery (EVS) have increased mortality independent of perioperative surgical outcome. To understand why high NLR is associated with higher mortality, we investigated neutrophil and lymphocyte transcriptome expression in patients undergoing EVS. Blood samples were collected from patients undergoing EVS and healthy donors for NLR calculation. RNA samples were isolated from patients' neutrophils and lymphocytes and divided into NLR_Low (<3) and NLR_High (≥3) groups (n = 6 each). Paired samples with the highest RNA integrity number (mean = 9.8 ± 0.4) were sequenced and analyzed for differential expression. Normalized data were inputted for downstream analysis using iPathwayGuide (AdvaitaBio) and gene set enrichment analysis using GenePattern and MSigDB (Broad Institute). There was no clinical difference between the patient groups with regard to clinical diagnosis, age, sex, history of hypertension, lipid abnormalities, diabetes mellitus, smoking, or statin use. The mean NLR was 4.37 ± 0.27 SEM in the NLR_High and 1.88 ± 0.16 for the NLR_Low groups. Significantly differentially expressed gene sets identified in the RNA sequence data were enriched highly (P = 1E-24) in the humoral immunity and complement systems. Neutrophils from NLR_High patients downregulated complement genes (C1QA, C1QB, C1QC, C1S, C2, CR2, C3AR1, C3, C8G, and C9 and complement regulatory genes CD59, SERPING1, C4BPA, CFH, and CFI). Downregulation of gene expressions of humoral immunity and complement within the neutrophils are associated with elevated NLR. It remains to be determined whether and how these changes contribute to increased late mortality previously observed in patients undergoing EVS.
Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
Authors: He Qian , Bennett Adam N. , Liu Jundong , Fan Beifang , Han Xue , Cheng Lu , Chen Yan , Yang Xia , Chan Kei Hang Katie
Published: August 2022

Individuals with schizophrenia (SCZ) have, on average, a 10- to 20-year shorter expected life span than the rest of the population, primarily due to cardiovascular disease comorbidity. Genome-wide association studies (GWAS) have previously been used to separately identify common variants in SCZ and cardiometabolic traits. However, genetic variants jointly influencing both traits remain to be fully characterised. To assess overlaps (if any) between the genetic architecture of SCZ and cardiometabolic traits, we used conditional false discovery rate (FDR) and local genetic correlation statistical framework analyses. A conjunctional FDR was used to identify shared genetic traits between SCZ and cardiometabolic risk factors. We identified 144 genetic variants which were shared between SCZ and body mass index (BMI), and 15 variants shared between SCZ and triglycerides (TG). Furthermore, we discovered four novel single nucleotide polymorphisms (SNPs) (rs3865350, rs9860913, rs13307 and rs9614186) and four proximate genes (DERL2, SNX4, LY75 and EFCAB6) which were shared by SCZ and BMI. We observed that the novel genetic variant rs13307 and the most proximate gene LY75 exerted potential effects on SCZ and BMI comorbidity. Also, we observed a mixture of concordant and opposite direction associations with shared genetic variants. We demonstrated a moderate to high genetic overlap between SCZ and cardiometabolic traits associated with a pattern of bidirectional associations. Our data suggested a complex interplay between metabolism-related gene pathways in SCZ pathophysiology.
Revised time estimation of the ancestral human chromosome 2 fusion
Authors: Poszewiecka Barbara , Gogolewski Krzysztof , Stankiewicz Paweł , Gambin Anna
Published: August 2022

Background

The reduction of the chromosome number from 48 in the Great Apes to 46 in modern humans is thought to result from the end-to-end fusion of two ancestral non-human primate chromosomes forming the human chromosome 2 (HSA2). Genomic signatures of this event are the presence of inverted telomeric repeats at the HSA2 fusion site and a block of degenerate satellite sequences that mark the remnants of the ancestral centromere. It has been estimated that this fusion arose up to 4.5 million years ago (Mya).

Results

We have developed an enhanced algorithm for the detection and efficient counting of the locally over-represented weak-to-strong (AT to GC) substitutions. By analyzing the enrichment of these substitutions around the fusion site of HSA2 we estimated its formation time at 0.9 Mya with a 95% confidence interval of 0.4-1.5 Mya. Additionally, based on the statistics derived from our algorithm, we have reconstructed the evolutionary distances among the Great Apes (Hominoidea).

Conclusions

Our results shed light on the HSA2 fusion formation and provide a novel computational alternative for the estimation of the speciation chronology.
Integrated transcriptomic and transgenic analyses reveal potential mechanisms of poplar resistance to Alternaria alternata infection
Authors: Huang Ying , Ma Huijun , Yue Yuanzhi , Zhou Tianchang , Zhu Zhenyu , Wang Chao
Published: August 2022

Background

Populus davidiana × P. bollenais a species of poplar from northeastern China that is characterized by cold resistance and fast growth but now suffers from pathogen infections. Leaf blight caused byAlternaria alternatahas become a common poplar disease that causes serious economic impacts, but the molecular mechanisms of resistance toA. alternatainP. davidiana × P. bollenaare still unclear.

Results

In this study, the transcriptomic response ofP. davidiana × P. bollenatoA. alternatainfection was determined via RNA-Seq. Twelve cDNA libraries were generated from RNA isolated from three biological replicates at four time points (0, 2, 3, and 4 d post inoculation), and a total of 5,930 differentially expressed genes (DEGs) were detected (| log2fold change |≥ 1 and FDR values < 0.05). Functional analysis revealed that the DEGs were mainly enriched for the “plant hormone signal transduction” pathway, followed by the “phenylpropanoid biosynthesis” pathway. In addition, DEGs that encode defense-related proteins and are related to ROS metabolism were also identified. Numerous transcription factors, such as the bHLH, WRKY and MYB families, were also induced byA. alternatainfection. Among these DEGs, those related to JA biosynthesis and JA signal transduction were consistently activated. Therefore, the lipoxygenase genePdbLOX2, which is involved in JA biosynthesis, was selected for functional characterization. Overexpression ofPdbLOX2enhanced the resistance ofP. davidiana × P. bollenatoA. alternata,whereas silencing this gene enhanced susceptibility toA. alternatainfection.

Conclusions

These results provide new insight into the molecular mechanisms of poplar resistance toA. alternatainfection and provide candidate genes for breeding resistant cultivars using genetic engineering.
Introducing quality clusters in general practice – a qualitative study of the experiences of cluster coordinators
Authors: Kousgaard Marius Brostrøm , Mikkelsen Thorbjørn Hougaard , Bundgaard Maria , Madsen Marie Henriette , Klausen Morten Bonde , Kristensen Mads Toft , Kjellberg Pia Kürstein , Søndergaard Jens
Published: August 2022

Background

In 2018, the concept of clusters was introduced as a new model for data-driven quality improvement in general practice in Denmark. However, there is little research on the development and implementation of general practice clusters. The study explores how the cluster coordinators responsible for leading the clusters forward enacted and experienced their role during the early years of the clusters with attention to the challenges and enablers perceived in the process.

Methods

Qualitative, semi-structured interviews with 25 cluster coordinators from clusters that had carried out at least two meetings on a specific professional topic. The coordinators represented clusters of varying sizes and different geographic locations. Key topics in the interview guide were the development and structure of the cluster, the role of the coordinator, obtainment of data for the meetings, the role of external support, the form and content of the meetings, the participation and engagement of the members. A thematic analysis – shaped by the original aims and categories of the study while also being open to emerging themes – was performed on the transcribed interview material.

Results

Important enablers in the process of developing the clusters included the positive engagement of the GPs, the support offered by regional quality units and a national quality organisation for general practice, and the funding provided by the formal cluster framework. Challenges initially included setting up the clusters administratively and translating the open cluster concept into a local, workable model; and later obtaining relevant data for the cluster meetings and facilitating peer discussions about the data.

Conclusion

The coordinators generally experienced that the development of the clusters had progressed relatively fast with engagement from most of the participating GPs. Still, challenges with data obtainment, data analysis, and facilitation will have to be addressed ongoingly. Future research should investigate learning processes at the cluster meetings and how the clusters impact clinical practice and collaborative relations between general practice and other health care providers.
The value of diffusion kurtosis imaging and intravoxel incoherent motion quantitative parameters in predicting synchronous distant metastasis of rectal cancer
Authors: Ding Xue , Sun Danqi , Guo Qiuchen , Li Yeting , Chen Hao , Dai Xiaoxiao , Fan Guohua , Wu Yongyou , Chen Guangqiang , Li Yonggang
Published: August 2022

Background

The incidence and mortality rate of rectal cancer are still high, the metastasis of rectal cancer are main causes of death. The control of the distant metastasis is one of the main concerns in the treatment of locally advanced rectal cancer, but there are few studies on predicting synchronous distant metastasis (SDM) of rectal cancer.

Method

The data of patients with rectal adenocarcinoma confirmed by endoscopic biopsy or postoperative pathology from September 2015 to May 2020 in hospital A (center 1) and hospital B (center 2) were analyzed retrospectively, including age, sex, carcinoembryonic antigen, carbohydrate antigen 19–9, tumor location, tumor length, image staging and characteristics. The average age of the 169 patients consisting of 105 males and 64 females in study is 61.2 years. All patients underwent rectal routine rectal MRI, DKI and IVIM examinations on a 3.0-T scanner. Two radiologists sketched regions of interest (ROIs) on b = 1000 s/mm2 DKI and IVIM images to obtain quantitative parameters with FireVoxel manually. We evaluated the difference of histogram analysis, clinical and image data between SDM group and non-SDM group, and evaluated the efficacy of each index in predicting SDM of rectal cancer.

Results

The 90th percentile of f values in the SDM group is lower than that in the non-SDM group (29.4 ± 8.4% vs. 35 ± 17.8%, P = 0.005). CA19-9 in the SDM group is higher than that in the non-SDM group (P = 0.003). Low and high rectal cancer are more likely to develop SDM than middle rectal cancer (P = 0.05 and P = 0.047). The combination of these three indexes has a greater area under the curve (AUC) than any one index (0.801 vs. 0.685 (f (90th percentile)) and 0.627 (CA19-9), P = 0.0075 and 0.0058, respectively), and its specificity and sensitivity are 80.0% and 71.6%, respectively. When this combination is incorporated into the predictive nomogram model, the c-index is 0.801 (95% confidence interval (CI): 0.730–0.871).

Conclusions

IVIM quantitative parameters combine with CA19-9 and tumor location can better predict the risk of SDM of rectal cancer.
The impact of the COVID-19 pandemic on children with medical complexity
Authors: Diskin Catherine , Buchanan Francine , Cohen Eyal , Dewan Tammie , Diaczun Tessa , Gordon Michelle , Lee Esther , MooreHepburn Charlotte , Major Nathalie , Orkin Julia , Patel Hema , Gill Peter J.
Published: August 2022

Background

Descriptions of the COVID-19 pandemic’s indirect consequences on children are emerging. We aimed to describe the impacts of the pandemic on children with medical complexity (CMC) and their families.

Methods

A one-time survey of Canadian paediatricians using the Canadian Paediatric Surveillance Program (CPSP) was conducted in Spring 2021.

Results

A total of 784 paediatricians responded to the survey, with 70% (n = 540) providing care to CMC. Sixty-seven (12.4%) reported an adverse health outcome due to a COVID-19 pandemic-related disruption in healthcare delivery. Disruption of the supply of medication and equipment was reported by 11.9% of respondents (n = 64). Respondents reported an interruption in family caregiving (47.5%,n = 252) and homecare delivery (40.8%,n = 218). Almost 47% of respondents (n = 253) observed a benefit to CMC due to COVID-19 related changes in healthcare delivery, including increased availability of virtual care and reduction in respiratory illness. Some (14.4%) reported that CMC were excluded from in-person learning when their peers without medical complexity were not.

Conclusion

Canadian paediatricians reported that CMC experienced adverse health outcomes during the COVID-19 pandemic, including disruptions to family caregiving and community supports. They also describe benefits related to the pandemic including the expansion of virtual care. These results highlight the need for healthcare, community and education policymakers to collaborate with families to optimize their health.
Access, utilization, and barriers to using malaria protection tools in migrants to Iran
Authors: Okati-Aliabad Hassan , Ansari-Moghaddam Alireza , Mohammadi Mahdi , Nejati Jalil , Ranjbar Mansour , Raeisi Ahmad , Kolifarhood Goodarz , Shahraki-Sanavi Fariba , Khorram Alireza
Published: August 2022

Background

Imported malaria cases could be considered one of the threats to malaria elimination. Therefore, increasing migrants’ access to malaria preventive measures can play an essential role in maintaining appropriate conditions and preventing malaria outbreaks. This study aimed to provide detailed information about access, utilization, and barriers to using malaria protection tools in migrants to Iran.

Methods

This study was conducted in a vast region consisting of 4 provinces and 38 cities located in the south and southeast of the country. Study participants were migrants who moved to the study area in the past three months. A sample of 4163 migrants participated in the study. They were selected through a multi-stage sampling method to obtain a representative community sample. Data were collected through interviewer-administered questionnaires about participants’ socio-demographic specification, commuting characteristics, travel aim, access, ways of preparing, and reasons to use or not to use malaria protection tools. Quantitative and qualitative variables were described and analyzed finally.

Results

The mean age of individuals was 28.6 ± 10.8, with a range of 3–88 years old. Migrants’ country of origin was Afghanistan (56.6%), Pakistan (38.4%), and Iran (5%). Most migrants (69.2%) did not have malaria protection tools while staying in Iran. Among those who procured the protection tools, 74% used long-lasting insecticidal nets (LLINs), 13.4% used mosquito repellent sticks and coil, and 12.7% did not use any tools. Respectively, lack of knowledge about where they can get LLINs, followed by being expensive, unavailability in the market, not cooperation of health officer, and no need to use were expressed as the causes for having no access. The main reasons for non-using the tools were lack of knowledge about their application, followed by a defect in protection tools, ineffectiveness, and being harmful, respectively. Migrants who were supported by an employer accessed more to LLINs.

Conclusions

This study reveals significant shortcomings in knowledge, access, and utilization of malaria protection tools among migrants in Iran. Inequitable access to public health services is predictable during migration; however, access to sustainable protection tools is recommended.