bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor VIII Trafficking to CD4+ T cells Shapes its Immunogenicity and Requires Several Types of Antigen Presenting Cells
Authors: Kaczmarek Radoslaw , Pineros Annie R. , Patterson Paige E , Bertolini Thais B. , Perrin George Q , Sherman Alexandra , Born Jameson , Arisa Sreevani , Arvin Matthew C , Kamocka Malgorzata M. , Martinez Irizarry Michelle M. , Dunn Kenneth W. , Quinn Sean M. , Morris Johnathan J. , Wilhelm Amelia R. , Kaisho Tsuneyasu , Munoz-Melero Maite , Biswas Moanaro , Kaplan Mark H , Linnemann Amelia K. , George Lindsey A. , Camire Rodney M. , Herzog Roland W
Published: May 2023

Despite over 80 years of clinical experience with coagulation factor (F)VIII inhibitors, surprisingly little is known about the in vivo mechanism of this most serious complication of replacement therapy for hemophilia A. These neutralizing anti-drug alloantibodies arise in ~30% of patients. Inhibitor formation is T cell-dependent, but events leading up to helper T cell activation have been elusive due in part to the complex anatomy and cellular makeup of the spleen. Here, we show that FVIII antigen presentation to CD4+ T cells critically depends on a select set of several anatomically distinct antigen presenting cells, whereby marginal zone B cells, marginal zone and marginal metallophilic but not red pulp macrophages (RPMFs) participate in shuttling FVIII to the white pulp where conventional dendritic cells (DCs) prime helper T cells, which then differentiate into follicular helper T (Tfh) cells. Toll-like receptor 9 (TLR9) stimulation accelerated Tfh responses, Germinal Center and inhibitor formation, while systemic administration of FVIII alone in hemophilia A mice increased frequencies of monocyte-derived and plasmacytoid DCs. Moreover, FVIII enhanced T cell proliferation to another protein antigen (ovalbumin), and inflammatory signaling-deficient mice were less likely to develop inhibitors, indicating that FVIII may have intrinsic immunostimulatory properties. Ovalbumin, which, unlike FVIII, is absorbed into the RPMF compartment, fails to elicit T cell proliferative and antibody responses when administered at the same dose as FVIII. Altogether, we propose that an antigen trafficking pattern that results in efficient in vivo delivery to DCs and inflammatory signaling, shape the immunogenicity of FVIII.
Structure of coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor
Authors: Childers Kenneth C , Avery Nathan G , Estrada Alamo Kevin Alexander , Davulcu Omar , Haynes Rose Marie , Lollar Pete , Doering Christopher B. , Coxon Carmen Helena , Spiegel Paul Clinton
Published: May 2023

The development of pathogenic antibody inhibitors against coagulation factor VIII (FVIII) occurs in approximately 30% of congenital hemophilia A patients receiving FVIII replacement therapy as well as in all cases of acquired hemophilia A. KM33 is an anti-C1 domain antibody inhibitor previously isolated from a severe hemophilia A patient. In addition to potently blocking FVIII binding to von Willebrand factor and phospholipid surfaces, KM33 disrupts FVIII binding to lipoprotein receptor-related protein 1 (LRP1), which drives FVIII hepatic clearance and antigen presentation in dendritic cells. Here, we report on the structure of FVIII bound to NB33, a recombinant derivative of KM33, by single-particle cryo-electron microscopy. Structural analysis reveals the NB33 epitope localizes to FVIII residues R2090-S2094 and I2158-R2159 which constitute membrane-binding loops in the C1 domain. Further analysis reveals multiple FVIII lysine and arginine residues, previously shown to mediate binding to LRP1, dock onto an acidic cleft at the NB33 variable domain interface, thus blocking a putative LRP1 binding site. Together, these results demonstrate a novel mechanism of FVIII inhibition by a patient-derived antibody inhibitor and provide structural evidence toward engineering FVIII with reduced LRP1-mediated clearance.
Parahippocampus hypertrophy drives gray matter morphological alterations in migraine patients without aura
Authors: Yin Tao , Lan Lei , Tian Zilei , Li Zhengjie , Liu Mailan , Gao Yujie , Liang Fanrong , Zeng Fang
Published: May 2023

Background

The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure.

Methods

A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine.

Results

MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients.

Conclusion

The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.
The role of gut microbiota on cognitive development in rodents: a meta-analysis
Authors: Putri Siti Sarahdeaz Fazzaura , Irfannuddin Irfannuddin , Murti Krisna , Kesuma Yudianita , Darmawan Hardi , Koibuchi Noriyuki
Published: May 2023

Cognitive function includes learning, remembering and using acquired information. Emerging studies indicate the correlation between microbiota and cognitive function. Higher abundance of a specific gut microbiota, such as Bacteroidetes may improve cognitive abilities. However, another study reported different result. These results suggest that further systematic analysis is required to determine the effect of the gut microbiota abundance on cognitive development. The aim of this study is to summarize the abundance of the specific gut microbiota and cognitive development using meta-analysis. PubMed, ScienceDirect, and Clinical-Key were used as data bases to perform the literature search. Phylum Bacteroidetes, and family Lactobacillaceae were more abundant in cognitive-behavioral enhancement (CBE), whereas Firmicutes, Proteobacteria, Actinobacteria, and family Ruminococcaceae were less abundant in CBE. Differences in gut microbiota abundance are influenced by differences in stage of cognitive dysfunction, intervention, and strain of gut microbiota.
CysPresso: a classification model utilizing deep learning protein representations to predict recombinant expression of cysteine-dense peptides
Authors: Ouellet Sébastien , Ferguson Larissa , Lau Angus Z. , Lim Tony K. Y.
Published: May 2023

Background

Cysteine-dense peptides (CDPs) are an attractive pharmaceutical scaffold that display extreme biochemical properties, low immunogenicity, and the ability to bind targets with high affinity and selectivity. While many CDPs have potential and confirmed therapeutic uses, synthesis of CDPs is a challenge. Recent advances have made the recombinant expression of CDPs a viable alternative to chemical synthesis. Moreover, identifying CDPs that can be expressed in mammalian cells is crucial in predicting their compatibility with gene therapy and mRNA therapy. Currently, we lack the ability to identify CDPs that will express recombinantly in mammalian cells without labour intensive experimentation. To address this, we developed CysPresso, a novel machine learning model that predicts recombinant expression of CDPs based on primary sequence.

Results

We tested various protein representations generated by deep learning algorithms (SeqVec, proteInfer, AlphaFold2) for their suitability in predicting CDP expression and found that AlphaFold2 representations possessed the best predictive features. We then optimized the model by concatenation of AlphaFold2 representations, time series transformation with random convolutional kernels, and dataset partitioning.

Conclusion

Our novel model, CysPresso, is the first to successfully predict recombinant CDP expression in mammalian cells and is particularly well suited for predicting recombinant expression of knottin peptides. When preprocessing the deep learning protein representation for supervised machine learning, we found that random convolutional kernel transformation preserves more pertinent information relevant for predicting expressibility than embedding averaging. Our study showcases the applicability of deep learning-based protein representations, such as those provided by AlphaFold2, in tasks beyond structure prediction.
Genome-wide analysis of the cellulose toolbox of Primulina eburnea, a calcium-rich vegetable
Authors: Zhang Yi , Zhang Jie , Zou Shuaiyu , Liu Ziwei , Huang Hongwen , Feng Chen
Published: May 2023

Background

Human-guided crop domestication has lasted for more than 10,000 years. In terms of the domestication and breeding of vegetables, cellulose content in edible tissues is one of the most important traits. Primulina eburnea is a recently developed calcium-rich vegetable with a high soluble and bioavailable calcium content in its leaves. However, the high cellulose content in the leaves hampers the taste, and no research has been reported on the genetic basis of cellulose biosynthesis in this calcium-rich vegetable.

Results

We identified 36 cellulose biosynthesis-involved genes belonging to eight gene families in the P. eburnea genome. The cellulose accumulated decreasingly throughout leaf development. Nineteen genes were considered core genes in cellulose biosynthesis, which were highly expressed in buds but lowly expressed in mature leaves. In the nitrogen fertilization experiment, exogenous nitrogen decreased the cellulose content in the buds. The expressing pattern of 14 genes were consistent with phenotypic variation in the nitrogen fertilization experiment, and thus they were proposed as cellulose toolbox genes.

Conclusions

The present study provides a strong basis for the subsequent functional research of cellulose biosynthesis-involved genes in P. eburnea, and provides a reference for breeding and/or engineering this calcium-rich vegetable with decreased leaf cellulose content to improve the taste.
After COVID-19 vaccinations: what does living and working in nursing homes look like?
Authors: Urlings Judith H. J. , Backhaus Ramona , Verbeek Hilde , de Boer Bram , Koopmans Raymond T.C.M. , Gerritsen Debby L. , Hamers Jan P.H.
Published: May 2023

Background

Nursing homes were disproportionally affected by the COVID-19 pandemic. Vaccination was considered critical for the normalization of daily live of nursing home residents. The present study investigates the impact of the prolonged COVID-19 pandemic and the effect of vaccinations on the daily lives of residents and staff in Dutch nursing homes.

Setting and participants

The sample consisted of 78 nursing homes that participated in the Dutch national pilot on nursing home visits after the COVID-19 pandemic. One contact person per nursing home was approached for participation in this mixed-methods cross-sectional study.

Methods

Data was collected twice through questionnaires in April and December 2021. Quantitative questions focused on recent COVID-19 outbreaks, progress of vaccination, effects of vaccination on daily living in the nursing home and burden experienced by staff. Open-ended questions addressed the prolonged effect of the pandemic on residents, family members and staff.

Results

The overall vaccination rate of residents across nursing homes appeared to be high among both residents and staff. However, daily living in the nursing home had not returned to normal concerning personal interactions, visits, the use of facilities and work pressure. Nursing homes continued to report a negative impact of the pandemic on residents, family members and staff.

Conclusions

Restrictions to the daily lives of residents in nursing homes were stricter than restrictions imposed on society as a whole. Returning to a normal daily living and working was found to be complex for nursing homes. With the emergence of new variants of the virus, policies strongly focusing on risk aversion were predominantly present in nursing homes.
Risk factors for SARS-CoV-2 seropositivity in a health care worker population during the early pandemic
Authors: Schubl Sebastian D. , Figueroa Cesar , Palma Anton M. , de Assis Rafael R. , Jain Aarti , Nakajima Rie , Jasinskas Algimantas , Brabender Danielle , Hosseinian Sina , Naaseh Ariana , Hernandez Dominguez Oscar , Runge Ava , Skochko Shannon , Chinn Justine , Kelsey Adam J. , Lai Kieu T. , Zhao Weian , Horvath Peter , Tifrea Delia , Grigorian Areg , Gonzales Abran , Adelsohn Suzanne , Zaldivar Frank , Edwards Robert , Amin Alpesh N. , Stamos Michael J. , Barie Philip S. , Felgner Philip L. , Khan Saahir
Published: May 2023

Background

While others have reported severe acute respiratory syndrome-related coronavirus 2(SARS-CoV-2) seroprevalence studies in health care workers (HCWs), we leverage the use of a highly sensitive coronavirus antigen microarray to identify a group of seropositive health care workers who were missed by daily symptom screening that was instituted prior to any epidemiologically significant local outbreak. Given that most health care facilities rely on daily symptom screening as the primary method to identify SARS-CoV-2 among health care workers, here, we aim to determine how demographic, occupational, and clinical variables influence SARS-CoV-2 seropositivity among health care workers.

Methods

We designed a cross-sectional survey of HCWs for SARS-CoV-2 seropositivity conducted from May 15th to June 30th 2020 at a 418-bed academic hospital in Orange County, California. From an eligible population of 5,349 HCWs, study participants were recruited in two ways: an open cohort, and a targeted cohort. The open cohort was open to anyone, whereas the targeted cohort that recruited HCWs previously screened for COVID-19 or work in high-risk units. A total of 1,557 HCWs completed the survey and provided specimens, including 1,044 in the open cohort and 513 in the targeted cohort. Demographic, occupational, and clinical variables were surveyed electronically. SARS-CoV-2 seropositivity was assessed using a coronavirus antigen microarray (CoVAM), which measures antibodies against eleven viral antigens to identify prior infection with 98% specificity and 93% sensitivity.

Results

Among tested HCWs (n = 1,557), SARS-CoV-2 seropositivity was 10.8%, and risk factors included male gender (OR 1.48, 95% CI 1.05–2.06), exposure to COVID-19 outside of work (2.29, 1.14–4.29), working in food or environmental services (4.85, 1.51–14.85), and working in COVID-19 units (ICU: 2.28, 1.29–3.96; ward: 1.59, 1.01–2.48). Amongst 1,103 HCWs not previously screened, seropositivity was 8.0%, and additional risk factors included younger age (1.57, 1.00-2.45) and working in administration (2.69, 1.10–7.10).

Conclusion

SARS-CoV-2 seropositivity is significantly higher than reported case counts even among HCWs who are meticulously screened. Seropositive HCWs missed by screening were more likely to be younger, work outside direct patient care, or have exposure outside of work.
ACSL4 serves as a novel prognostic biomarker correlated with immune infiltration in Cholangiocarcinoma
Authors: Liu Shuochen , Fan Shilong , Wang Yirui , Chen Ruixiang , Wang Ziyi , Zhang Yaodong , Jiang Wangjie , Chen Yananlan , Xu Xiao , Yu Yue , Li Changxian , Li Xiangcheng
Published: May 2023

Background

Cholangiocarcinoma (CHOL) is the second most common primary hepatic malignant tumor, following hepatocellular carcinoma (HCC). CHOL is highly aggressive and heterogeneous resulting in poor prognosis. The diagnosis and prognosis of CHOL has not improved in the past decade. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is reported to be associated with tumors, however, its role in CHOL has not been revealed. This study is mainly for exploring the prognostic values and potential function of ACSL4 in CHOL.

Methods

We investigated the expression level and prognostic value of ACSL4 in CHOL based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. TIMER2.0, TISIDB and CIBERSORT databases were utilized to assess the associations between ACSL4 and immune infiltration cells in CHOL. Single-cell sequencing data from GSE138709 was analyzed to study the expression of ACSL4 in different types of cells. ACSL4 co-expressed genes were analyzed by Linkedomics. Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and wound healing assay were performed to further confirm the roles of ACSL4 in the pathogenesis of CHOL.

Results

We found that the level of ACSL4 was higher in CHOL and it was correlated with the diagnosis and prognosis of CHOL patients. Then, we observed that the infiltration level of immune cells was related to the level of ACSL4 in CHOL. Moreover, ACSL4 and its co-expressed genes were mainly enriched in metabolism-related pathway and ACSL4 is also a key pro-ferroptosis gene in CHOL. Finally, knockdown of ACSL4 could reverse the tumor-promoting effect of ACSL4 in CHOL.

Conclusions

The current findings demonstrated ACSL4 may as a novel biomarker for CHOL patients, which might regulate immune microenvironment and metabolism resulting in poor prognosis.
Cardiovascular risk profiles clusters among children and adolescents with disabilities
Authors: Yehuda Maayan Bar , Barak Sharon , Hutzler Yeshayahu , Ng Kwok , Giladi Ariela , Meir Lilach Bar , Marques Adilson , Zigdon Avi , Zwilling Moti , Reges Orna , Fisch Yossi Harel , Tesler Riki
Published: May 2023

Background

Cardiovascular diseases (CVD) are a precursor for disabilities and death worldwide. Being overweight or obese in combination with physical inactivity and smoking habits may increase the risk for CVD and other health problems such as lower limb osteoarthritis, diabetes, stroke, and various cancer types among children and adolescents. The literature emphasizes the need to follow such groups and evaluate the risk of individuals developing CVD diseases. Therefore, the current study explores the variety of cardiovascular risks in children and adolescents’ profiles clusters with and without disabilities.

Methods

Data from 42 countries including Israel, was collected with the support of the world health organization (WHO, Europe) through a questionnaire from 11–19 years old school-aged.

Results

The study finding shows that children and adolescents with disabilities demonstrated a higher prevalence of overweight than those who completed the HBSC youth behavior survey. Moreover, the prevalence of tobacco smoking and alcohol use was statisticaly significantly higher among the disabled group than the non-disabled group. In addition, socioeconomic status of responders who presented a very high CVD risk was found as significantly lower than those from the first and second low risk groups.

Conclusion

This led to the conclusion that children and adolescents with disability were at a higher risk of developing CVDs than their non-disabled peers. In addition, intervention programs tailored to the needs of adolescents with disability should consider lifestyle habit change and promoting healthy living thus improving their quality of life as well as reducing their risk of being exposed to severe CVD diseases.
Left parathyroid carcinoma with secondary hyperparathyroidism: a case report
Authors: Yokoyama Ko , Suganuma Nobuyasu , Rino Yasushi
Published: May 2023

Background

Parathyroid carcinoma is a rare disease with a frequency of 0.005% of all malignancies [1, 2]. Various aspects of its pathogenesis, diagnosis, and treatment remain poorly understood. Furthermore, cases with secondary hyperparathyroidism are fewer. In this case report, we describe a case of left parathyroid carcinoma with secondary hyperparathyroidism.

Case presentation

The patient was a 54-year-old woman who had been on hemodialysis since the age of 40 years. At 53 years of age, her calcium levels were high, and she was diagnosed with drug-resistant secondary hyperparathyroidism and was referred to our hospital for surgical treatment. Blood tests revealed calcium levels of 11.4 mg/dL and intact parathyroid hormone (PTH) levels of 1007 pg/mL. Neck ultrasonography revealed a 22-mm large round hypoechoic mass, partially indistinct margins, and D/W ratio > 1 at the left thyroid lobe. Computed tomography scans revealed a 20-mm nodule at the left thyroid lobe. No enlarged lymph nodes or distant metastases were noted. 99mTc-hexakis-2-methoxyisobutylisonitrile scintigraphy revealed an accumulation at the superior pole of the left thyroid lobe. Laryngeal endoscopy revealed paralysis of the left vocal cord, signifying recurrent nerve palsy due to parathyroid carcinoma. Based on these results, a diagnosis of secondary hyperparathyroidism and suspected left parathyroid carcinoma was made, and the patient underwent surgery. Pathology results revealed hyperplasia in the right upper and lower parathyroid glands. The left upper parathyroid gland showed capsular and venous invasion, and the diagnosis was left parathyroid carcinoma. At 4 months post-surgery, calcium levels improved to 8.7 mg/dL and intact PTH levels to 20 pg/mL, with no signs of recurrence.

Conclusions

We report a case of left parathyroid carcinoma associated with secondary hyperparathyroidism. Concomitant secondary hyperparathyroidism may cause mild hypercalcemia compared to parathyroid carcinoma alone due to the added modification of dialysis. Although our patient also presented with mild hypercalcemia, a D/W ratio > 1 on preoperative echocardiography and presence of recurrent nerve palsy on laryngoscopy led to the suspicion and treatment of parathyroid carcinoma preoperatively.
Effects of crown-to-implant ratio on marginal bone level and bone density in non-splinted single implants: a cross-sectional study
Authors: Chen Ziyuan , Li Weiting , Li Peng
Published: May 2023

Background

Few studies have evaluated the effects of the crown-to-implant (C/I) ratio on the marginal bone level (MBL) and bone density in non-splinted single implants. The aim of this study was to assess the effect of C/I ratio on MBL and density of peri-implant bone in non-splinted posterior implants.

Methods

The C/I ratio, MBL, and grayscale values (GSVs) for bone density were measured from X-rays. Four areas of interest (two at the apical area and two at the middle of the peri-implant area) and two control areas were selected for evaluation. Follow-up radiographs were calibrated according to the control areas.

Results

In all, 117 non-splinted posterior implants in 73 patients followed up for a mean duration of 36.23 ± 10.40 (range 24–72) months were considered. The mean anatomical C/I ratio was 1.78 ± 0.43 (range 0.93 to 3.06). The mean change in MBL was 0.28 ± 0.97 mm. There were no significant associations between the C/I ratio and MBL changes (r = -0.028, p = 0.766). Pearson correlation showed a significant correlation between changes in GSV and the C/I ratio in the middle peri-implant area (r = 0.301, p = 0.001) and apical area (r = 0.247, p = 0.009).

Conclusions

A higher C/I ratio of single non-splinted posterior implants is associated with increased peri-implant bone density, but not correlated with changes in MBL.
e-PBL with multimedia animations: a design-based research
Authors: Budakoğlu Işıl İrem , Coşkun Özlem , Özeke Vildan
Published: May 2023

Background

This study was conducted to explore the effectiveness of online problem-based learning (e-PBL) with multimedia animation scenarios by comparing the face-to-face (f2f) PBL method with paper-based scenarios. Adapting different f2f teaching methodologies to online environments is a significant problem that urgently needs attention, particularly in health education.

Methods

This study is part of design-based research and consists of three phases, which comprise design, analysis, and re-design. First, the animation-based problem scenarios were developed, and the learning environment (e-PBL) elements were organized. Then animation-based scenarios and the e-PBL environment were used, and problems related to the use of the environment were determined with an experimental study which was based on a pretest-posttest control group design. Finally, we used the following three measurement tools in the data collection process: a scale to determine the effectiveness of PBL, an attitude scale toward PBL, and the Clinical Objective Reasoning Exams (CORE). The study group in this research comprised 92 medical undergraduates (47 female and 45 male).

Results

There were similar scores between the two groups (e-PBL and f2f) in terms of the effectiveness of the platforms, the attitudes of the medical undergraduates, and the CORE scores. Also, there were positive relationships between the attitude scores, grade point average (GPA), and PBL scores of the undergraduates. Another significant positive relationship was found between the CORE scores and the GPA.

Conclusions

The animation-supported e-PBL environment positively effects the participants’ knowledge, skills, and attitude. Students who have high academic scores attitude positively towards e-PBL. Providing problem scenarios as multimedia animations is the innovative face of the research. They have been produced inexpensively with off-the-shelf web-based animation apps. These technological advances may democratize the production of video-based cases in the future. Although the results of this study were obtained before the pandemic, they showed no differences between e-PBL and f2f-PBL in terms of effectiveness.
Exploring lemology teaching with “internet plus” flipped classroom pedagogy
Authors: Cao Yu-Xin , Xia Shu-Lin , Zhu Zheng-Yun , Zeng Fan-Rong , Li Hai-Ning , Zhang Ting-Ting , Liu Yong-Juan
Published: May 2023

Background

To investigate the use of flipped classroom pedagogy based on “Internet plus” in teaching viral hepatitis in the lemology course during the COVID-19 epidemic.

Methods

This study included students from the clinical medicine general practitioner class at Nanjing Medical University’s Kangda College, with the observation group consisting of 67 students from the 2020–2021 school year and the control group consisting of 70 students from the 2019–2020 school year. The observation group used “Internet plus” flipped classroom pedagogy, while the control group used conventional offline instruction. The theory course and case analysis ability scores from the two groups were compared and analyzed, and questionnaire surveys were administered to the observation group.

Result

After the flipped classroom, the observation group had significantly higher theoretical test scores (38.62 ± 4.52) and case analysis ability scores (21.08 ± 3.58) than the control group (37.37 ± 2.43) (t = 2.024, P = 0.045) and (19.16 ± 1.15) (t = 4.254, P < 0.001), respectively. The questionnaire survey in the observation group revealed that the “Internet plus” flipped classroom pedagogy approach can help enhance students’ enthusiasm to learn, clinical thinking ability, practical application ability, and learning efficiency, with satisfaction rates of 81.7%, 85.0%, 83.3%, and 78.8%, respectively; 89.4% of students expressed hope that whenever physical classes resumed, the offline courses could be combined with this pedagogy approach.

Conclusion

The use of the “Internet plus” flipped classroom pedagogy technique for teaching viral hepatitis in a lemology course boosted students’ theory learning ability as well as their case analysis ability. The majority of students were pleased with this type of instruction and hoped that whenever physical classes resumed, the offline courses may be integrated with the “Internet plus” flipped classroom pedagogical approach.
Adaptation and psychometric testing of the end-of-life professional caregiver survey in Jamaica
Authors: Edwards Rebecca L. , Bakitas Marie , Li Peng , Spence Dingle , Kahwa Eulalia , Stoltenberg Mark , Ivankova Nataliya V. , Thomas Kaesha , Segree Kammar , Kodilinye Syed Matthew , Markaki Adelais
Published: May 2023

Background

Using a validated instrument to measure palliative care (PC) educational needs of health professionals is an important step in understanding how best to educate a well-versed PC workforce within a national health system. The End-of-life Professional Caregiver Survey (EPCS) was developed to measure U.S. interprofessional PC educational needs and has been validated for use in Brazil and China. As part of a larger research project, this study aimed to culturally adapt and psychometrically test the EPCS among physicians, nurses, and social workers practicing in Jamaica.

Methods

Face validation involved expert review of the EPCS with recommendations for linguistic item modifications. Content validation was carried out by six Jamaica-based experts who completed a formal content validity index (CVI) for each EPCS item to ascertain relevancy. Health professionals practicing in Jamaica (n = 180) were recruited using convenience and snowball sampling to complete the updated 25-item EPCS (EPCS-J). Internal consistency reliability was assessed using Cronbach’s$$\alpha$$coefficient and McDonald’s$$\phi$$. Construct validity was examined through confirmatory factor analysis (CFA) and exploratory factor analysis (EFA).

Results

Content validation led to elimination of three EPCS items based on a CVI < 0.78. Cronbach’s$$\alpha$$ranged from 0.83 to 0.91 and McDonald’s$$\phi$$ranged from 0.73 to 0.85 across EPCS-J subscales indicating good internal consistency reliability. The corrected item-total correlation for each EPCS-J item was > 0.30 suggesting good reliability. The CFA demonstrated a three-factor model with acceptable fit indices (RMSEA = 0.08, CFI = 0.88, SRMR = 0.06). The EFA determined a three-factor model had the best model fit, with four items moved into theeffective patient caresubscale from the other two EPCS-J subscales based on factor loading.

Conclusions

The psychometric properties of the EPCS-J resulted in acceptable levels of reliability and validity indicating that this instrument is suitable for use in measuring interprofessional PC educational needs in Jamaica.
Cost-utility analysis of different venous access devices in breast cancer patients: a decision-based analysis model
Authors: Chen Na , Yang Qing , Li Yin Feng , Guo Qin , Huang De Yu , Peng Jia Ling
Published: May 2023

Background

Venous access devices commonly used in clinical practice for long-term chemotherapy of breast cancer include central venous catheters (CVCs), peripherally inserted central venous catheters (PICCs), and implantable venous access ports (IVAPs). CVCs and PICCs are less costly to place but have a higher complication rate than IVAPs. However, there is a lack of cost-utility comparisons among the three devices. The aim of this study was to assess the cost-effectiveness of three catheters for long-term chemotherapy in breast cancer patients.

Methods

This study used propensity score matching (PSM) to establish a retrospective cohort. Decision tree models were used to compare the cost-effectiveness of three different intravenous lines in breast cancer chemotherapy patients. Cost parameters were derived from data extracted from the outpatient and inpatient charging systems, and total costs included costs of placement, maintenance, extraction, and handling of complications; utility parameters were derived from previous cross-sectional survey results of the research group; and complication rates were derived from breast cancer catheterization patient information as well as follow-up information. Quality-adjusted life years (QALYs) were measured for efficacy outcomes. Incremental cost-effectiveness ratios (ICERs) were used to compare the three strategies. To assess uncertainty in model parameters, sensitivity analyses (univariate sensitivity analysis and probabilistic sensitivity analysis) were performed.

Results

A total of 10,718 patients (3780 after propensity score matching) were included. IVAPs had the smallest cost-utility ratio, and PICCs had the largest cost-utility ratio when left in place for more than 12 months. The incremental cost-utility ratio of PICC to CVC was $2375.08/QALY, IVAP to PICC was $522.01/QALY, and IVAP to CVC was $612.98/QALY. Incremental cost-effectiveness ratios showed that IVAPs were more effective than CVCs and PICCs. Model regression analysis showed that the IVAP was recommended as the best regimen regardless of the catheter indwelling time (6 months, 12 months or more than 12 months). The reliability and stability of the model were verified by single-factor sensitivity analysis and Monte Carlo simulation (probabilistic sensitivity analysis).

Conclusion

This study provides economic evidence for the selection of vascular access in breast cancer chemotherapy patients. In the case of limited resources in China, establishing a decision tree model comparing the cost-effectiveness of three vascular access devices for breast cancer chemotherapy patients determined that the IVAP was the most cost-effective regimen.
Safety culture in the operating room: translation, validation of the safety attitudes questionnaire – operating room version
Authors: Pevec Teodor , Albreht Tit , Turk Eva
Published: May 2023

Background

Measuring the safety culture in Healthcare is an important step in improving patient safety. One of the most commonly used instruments to measure the safety climate is the Safety Attitudes Questionnaire (SAQ). The aim of the current study was to establish the validity and reliability of the Slovenian version of the SAQ for the operating room SAQ-OR.

Methods

The SAQ, consisting of six dimensions, was translated and adapted to the Slovenian context and applied in operating rooms from seven out of ten Slovenian regional hospitals. Cronbach’s alpha and confirmatory factor analysis (CFA) was used to evaluate the reliability and validity of the instrument.

Results

The sample consisted of 243 health care professionals who hold positions in the OR, divided into 4 distinct professional classes, namely, 76 surgeons (31%), 15 anesthesiologists (6%), 140 nurses (58%) and 12 auxiliary persons (5%). It was observed a very good Cronbach's alpha (0.77 to 0.88). The CFA and its goodness-of-fit indices (CFI 0.912, TLI 0.900, RMSE 0.056, SRMR 0.056) showed an acceptable model fit. There are 28 items in the final model.

Conclusions

The Slovenian version of the SAQ-OR revealed good psychometric properties for studying the organisational safety culture.
Epigenetic reprogramming of Runx3 reinforces CD8 + T-cell function and improves the clinical response to immunotherapy
Authors: Liu Zongzhi , Li Xiang , Gao Yibo , Liu Jiejie , Feng Yating , Liu Yang , Wang Junyun , Wang Chunmeng , Wang Dongrui , He Jie , Han Weidong , Mei Qian , Sun Yingli
Published: May 2023

Background

Checkpoint blockade immunotherapy, represented by PD-1 or PD-L1 antibody treatment, has been of tremendous success in clinical practice. However, the low clinical response rate and lack of biomarkers for prediction of the immune response limit the clinical application of anti-PD-1 immunotherapy. Our recent work showed that a combination of low-dose decitabine and PD-1-ab significantly improved the complete response (CR) rate of cHL patients from 32 to 71%, which indicates that there is a significant correlation between epigenetic regulation and the clinical response to immunotherapy.

Methods

We recruited two groups of Hodgkin lymphoma patients who were treated with anti-PD-1 and DAC+anti-PD-1. CD8+ T cells were isolated from the patients' peripheral blood, DNA methylation was analyzed by EPIC, the expression profile was analyzed by RNA-seq, and multigroup analysis was performed with IPA and GSEA functional annotations. We explored the effect of DAC on the function of CD8+ T cells in the blood, spleen, tumor and lymph nodes using a mouse model. Furthermore, we explored the function of Tils in the tumor microenvironment. Then, we constructed Runx3-knockout mice to confirm the T-cell-specific function of Runx3 in CD8+ T cells and analyzed various subtypes of T cells and cytokines using mass cytometry (CyTOF).

Results

Multiomics analysis identified that DNA methylation reprogramming of Runx3 was a crucial mediator of CD8+ T-cell function. Multiomics data showed that reversal of methylation of the Runx3 promoter promoted the infiltration of CD8+ TILs and mitigated the exhaustion of CD8+ T cells. Furthermore, experiments on tissue-specific Runx3-knockout mice showed that Runx3 deficiency reduced CD8+ T infiltration and the differentiation of effector T and memory T cells. Furthermore, Runx3 deficiency significantly decreased CCR3 and CCR5 levels. Immunotherapy experiments in Runx3 conditional knockout mice showed that DAC could not reverse the resistance of anti-PD-1 in the absence of Runx3. Moreover, both our clinical data and data from TISIDB showed that Runx3 could be a potential biomarker for immunotherapy to predict the clinical response rate.

Conclusion

We demonstrate that the DNA methylation of Runx3 plays a critical role in CD8+ T-cell infiltration and differentiation during decitabine-primed PD-1-ab immunotherapy, which provides a supporting mechanism for the essential role of epiregulation in immunotherapy.
Manipulating facial musculature with functional electrical stimulation as an intervention for major depressive disorder: a focused search of literature for a proposal
Authors: Demchenko Ilya , Desai Naaz , Iwasa Stephanie N. , Gholamali Nezhad Fatemeh , Zariffa José , Kennedy Sidney H. , Rule Nicholas O. , Cohn Jeffrey F. , Popovic Milos R. , Mulsant Benoit H. , Bhat Venkat
Published: May 2023

Background

Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new “mind-body” intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD.

Methods

A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD.

Results

A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury may enhance central neuroplasticity, restoring lost sensorimotor function. These neuroplastic effects suggest that FES may be a promising innovative intervention for psychiatric disorders of disrupted brain connectivity, such as MDD. Recent pilot data on repetitive FES applied to the facial muscles in healthy participants and patients with MDD show early promise, suggesting that FES may attenuate the negative interoceptive bias associated with MDD by enhancing positive facial feedback. Neurobiologically, the amygdala and nodes of the emotion-to-motor transformation loop may serve as potential neural targets for facial FES in MDD, as they integrate proprioceptive and interoceptive inputs from muscles of facial expression and fine-tune their motor output in line with socio-emotional context.

Conclusions

Manipulating facial muscles may represent a mechanistically novel treatment strategy for MDD and other disorders of disrupted brain connectivity that is worthy of investigation in phase II/III trials.
Pathological characteristics and immune microenvironment of SMARCA4-deficient undifferentiated uterine sarcoma
Authors: Gao Jie , Fan Ruirui , Chen Dahong , Hou Jinlin , Chen Hanlin , Lu Mingzhi
Published: May 2023

SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a highly invasive single-gene malignant tumor caused by mutations in the SMARCA4 gene. SDUS has a poor prognosis, with no established treatment strategy at present. Further, there is a lack of relevant research on the role of the immune microenvironment in SDUS worldwide. Here, we report a case of SDUS that was diagnosed and analysed using morphological, immunohistochemical, and molecular detection techniques, along with the analysis of the immune microenvironment. By immunohistochemistry, the tumor cells showed retained INI-1 expression, focal CD10 expression, and loss of BRG1, CK-pan, synaptophysin, desmin, and ER expression. Further, some of the immune cells expressing CD3 and CD8 had infiltrated into the SDUS, but no PD-L1 expression was detected. The multiple immunofluorescent staining results showed that a proportion of the immune cells and SDUS cells expressed CD8/CD68/PD-1/PD-L1. Therefore, our report will help in the diagnostic awareness of SDUS.
Comparison of postoperative analgesic effects of erector spinae plane block and quadratus lumborum block in laparoscopic liver resection: study protocol for a randomized controlled trial
Authors: Bang Yu Jeong , Kwon Ji-Hye , Kang RyungA , Kim Gaab Soo , Jeong Ji Seon , Kim Myungsuk , Choi Gyu-Seong , Kim Jong Man , Ko Justin Sangwook
Published: May 2023

Background

Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection.

Methods

One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared.

Discussion

This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population.

Trial registration

Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599.
Potential distribution of Leptotrombidium scutellare in Yunnan and Sichuan Provinces, China, and its association with mite-borne disease transmission
Authors: Song Wen-Yu , Lv Yan , Yin Peng-Wu , Yang Yi-Yu , Guo Xian-Guo
Published: May 2023

Background

Leptotrombidium scutellare is one of the six main vectors of scrub typhus in China and is a putative vector of hemorrhagic fever with renal syndrome (HFRS). This mite constitutes a large portion of the chigger mite community in southwest China. Although empirical data on its distribution are available for several investigated sites, knowledge of the species’ association with human well-being and involvement in the prevalence of mite-borne diseases remains scarce.

Methods

Occurrence data on the chigger mite were obtained from 21 years (2001–2021) of field sampling. Using boosted regression tree (BRT) ecological models based on climate, land cover and elevation variables, we predicted the environmental suitability for L. scutellare in Yunnan and Sichuan Provinces. The potential distribution range and shifts in the study area for near-current and future scenarios were mapped and the scale of L. scutellare interacting with human activities was evaluated. We tested the explanatory power of the occurrence probability of L. scutellare on incidences of mite-borne diseases.

Results

Elevation and climate factors were the most important factors contributing to the prediction of the occurrence pattern of L. scutellare. The most suitable habitats for this mite species were mainly concentrated around high-elevation areas, with predictions for the future showing a trend towards a reduction. Human activity was negatively correlated with the environmental suitability of L. scutellare. The occurrence probability of L. scutellare in Yunnan Province had a strong explanatory power on the epidemic pattern of HFRS but not scrub typhus.

Conclusions

Our results emphasize the exposure risks introduced by L. scutellare in the high-elevation areas of southwest China. Climate change may lead to a range contraction of this species towards areas of higher elevation and lessen the associated exposure risk. A comprehensive understanding of the transmission risk requires more surveillance efforts.

Graphical Abstract