bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmasking the suppressed immunopeptidome of EZH2-mutated diffuse large B-cell lymphomas through combination drug treatment
Authors: Bourne Christopher M. , Mun Sung Soo , Dao Tao , Aretz Zita E. H. , Molvi Zaki , Gejman Ron S. , Daman Andrew , Takata Katsuyoshi , Steidl Christian , Klatt Martin G. , Scheinberg David A.
Published: May 2022

Exploring the repertoire of peptides presented on major histocompatibility complexes (MHCs) helps identify targets for immunotherapy in many hematologic malignancies. However, there is a paucity of such data for diffuse large B-cell lymphomas (DLBCLs), which might be explained by the profound downregulation of MHC expression in many DLBCLs, and in particular in the enhancer of zeste homolog 2 (EZH2)-mutated subgroup. Epigenetic drug treatment, especially in the context of interferon-γ (IFN-γ), restored MHC expression in DLBCL. In DLBCL, peptides presented on MHCs were identified via mass spectrometry after treatment with tazemetostat or decitabine alone or in combination with IFN-γ. Such treatment synergistically increased the expression of MHC class I surface proteins up to 50-fold and the expression of class II surface proteins up to threefold. Peptides presented on MHCs increased to a similar extent for both class I and class II MHCs. Overall, these treatments restored the diversity of the immunopeptidome to levels described in healthy B cells for 2 of 3 cell lines and allowed the systematic search for new targets for immunotherapy. Consequently, we identified multiple MHC ligands from the regulator of G protein signaling 13 (RGS13) and E2F transcription factor 8 (E2F8) on different MHC alleles, none of which have been described in healthy tissues and therefore represent tumor-specific MHC ligands that are unmasked only after drug treatment. Overall, our results show that EZH2 inhibition in combination with decitabine and IFN-γ can expand the repertoire of MHC ligands presented on DLBCLs by revealing suppressed epitopes, thus allowing the systematic analysis and identification of new potential immunotherapy targets.
Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study
Authors: Jang Jun Ho , Wong Lily , Ko Bor-Sheng , Yoon Sung-Soo , Li Katie , Baltcheva Irina , Nidamarthy Prasanna Kumar , Chawla Raghav , Junge Guido , Yap Eng Soo
Published: May 2022

Iptacopan (LNP023) is a novel, oral selective inhibitor of complement factor B under clinical development for paroxysmal nocturnal hemoglobinuria (PNH). In this ongoing open-label phase 2 study, PNH patients with active hemolysis were randomized to receive single-agent iptacopan twice daily at a dose of either 25 mg for 4 weeks followed by 100 mg for up to 2 years (cohort 1) or 50 mg for 4 weeks followed by 200 mg for up to 2 years (cohort 2). At the time of interim analysis, of 13 PNH patients enrolled, all 12 evaluable for efficacy achieved the primary endpoint of reduction in serum lactate dehydrogenase (LDH) levels by ≥60% by week 12 compared with baseline; mean LDH levels dropped rapidly and durably, namely by 77% and 85% at week 2 and by 86% and 86% at week 12 in cohorts 1 and 2, respectively. Most patients achieved a clinically meaningful improvement in hemoglobin (Hb) levels, and all but 1 patient remained transfusion-free up to week 12. Other markers of hemolysis, including bilirubin, reticulocytes, and haptoglobin, showed consistent improvements. No thromboembolic events were reported, and iptacopan was well tolerated, with no severe or serious adverse events reported until the data cutoff. In addition to the previously reported beneficial effect of iptacopan add-on therapy to eculizumab, this study showed that iptacopan monotherapy in treatment-naïve PNH patients resulted in normalization of hemolytic markers and rapid transfusion-free improvement of Hb levels in most patients. This trial was registered at www.clinicaltrials.gov as #NCT03896152.
Studies on pre-treatment by compression for wood impregnation III: effects of the solid content of low-molecular-weight phenol formaldehyde resin on the impregnation
Authors: Wang Huifang , Zhao Youke
Published: May 2022

There is increasing interests in the significant improvement of impregnation amount and efficiency in wood by the pre-treatment of compression. Thus, attention is paid to pre-treatment by compression for harder impregnation with resin because of the large viscosity and relatively large molecular weight of the resin. Low-molecular-weight phenol formaldehyde (PF) resin of solid content of 10–48% were impregnated by pre-treatment of compression at a compression ratio of 60% and 40% for poplar and Chinese fir, respectively, to systematically study the effects of solid content on the impregnation amount, weight gain percentage (WGP). In addition, the distribution of resin in wood was analyzed by profile density and was observed by confocal laser scanning microscope (CLSM), and the change of crystallinity index (CrI) of resin-impregnated wood was investigated by X-ray diffractometer. The results showed: (1) compared with immersion impregnation without compression, the impregnation by pre-treatment of compression, was much larger in amount and higher in efficiency for resins in all solid contents. In a solid content range of 10–48% and at a molecular weight of about 517, there was no significant difference of impregnation amount by compression among the resins at different solid content. (2) The WGP of poplar and Chinese fir increased with the increase of resin solid content. When the resin solid content increased from 10 to 48%, the WGP increased from 8.9 to 44.2% and from 5.2 to 24.9% for poplar and Chinese fir, respectively. (3) Resin is mainly distributed in vessels and tracheids despite a few being distributed in the fiber near the longitudinal end of the poplar specimens. With the increase of solid content, the resin distribution gradually changed from diffusing on the wall to depositing in the vessel or tracheid, while the resin distribution evenness along the longitudinal direction decreased. There was more resin deposited near the longitudinal end of Chinese fir at deeper depth than that of poplar. (4) The resin can be impregnated into the amorphous area of wood without causing any change in the crystallization area. The CrI decreases with the increase of resin solid content. After all, it is concluded that the pre-treatment by compression for wood impregnation with low-molecular-weight PF resin is effective for all the solid contents for both poplar and Chinese fir. The WGP increased with the increase of resin solid content, despite the decrease of evenness of resin distribution at high solid content.
Lectins and lectibodies: potential promising antiviral agents
Authors: Nabi-Afjadi Mohsen , Heydari Morteza , Zalpoor Hamidreza , Arman Ibrahim , Sadoughi Arezoo , Sahami Parisa , Aghazadeh Safiyeh
Published: May 2022

In nature, lectins are widely dispersed proteins that selectively recognize and bind to carbohydrates and glycoconjugates via reversible bonds at specific binding sites. Many viral diseases have been treated with lectins due to their wide range of structures, specificity for carbohydrates, and ability to bind carbohydrates. Through hemagglutination assays, these proteins can be detected interacting with various carbohydrates on the surface of cells and viral envelopes. This review discusses the most robust lectins and their rationally engineered versions, such as lectibodies, as antiviral proteins. Fusion of lectin and antibody’s crystallizable fragment (Fc) of immunoglobulin G (IgG) produces a molecule called a “lectibody” that can act as a carbohydrate-targeting antibody. Lectibodies can not only bind to the surface glycoproteins via their lectins and neutralize and clear viruses or infected cells by viruses but also perform Fc-mediated antibody effector functions. These functions include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell-mediated phagocytosis (ADCP). In addition to entering host cells, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein S1 binds to angiotensin-converting enzyme 2 (ACE2) and downregulates it and type I interferons in a way that may lead to lung disease. The SARS-CoV-2 spike protein S1 and human immunodeficiency virus (HIV) envelope are heavily glycosylated, which could make them a major target for developing vaccines, diagnostic tests, and therapeutic drugs. Lectibodies can lead to neutralization and clearance of viruses and cells infected by viruses by binding to glycans located on the envelope surface (e.g., the heavily glycosylated SARS-CoV-2 spike protein).
Diagnostic and prognostic values of pyroptosis-related genes for the hepatocellular carcinoma
Authors: Xing Mindan , Li Jia
Published: May 2022

Background

Due to the high heterogeneity, the early diagnosis and prognostic prediction of hepatic cellular cancer (HCC) is challenging. In this study, we explored the diagnostic and prognostic value of pyroptosis-related genes (PRGs) in HCC. We downloaded the mRNA expression profiles of HCC and the corresponding clinical data from the TCGA and ICGC databases. Fifty-one PRGs were extracted from Genecards, MsigDB, and relevant literature. The area under the receiver operating characteristic (AUC) was used to explore the diagnostic value of the PRGs.

Results

The results revealed that BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC, and GSDMD had higher diagnostic values for HCC (AUCs > 0.8, P < 0.05). Then, univariate and multivariate analyses of 51 PRGs were performed for HCC samples, and 4 PRGs (TP53, GPX4, GSDMC, BAK1) associated with HCC prognosis were obtained and used to construct a pyroptosis-related risk model. HCC samples were divided into high-risk and low-risk groups based on the risk score’s cut-off. Kaplan–Meier curve and Log-rank test were used to compare the overall survival (OS) of two risk groups. The OS was lower in the high-risk group than in the low-risk group. In addition, the time-dependent receiver operating characteristics revealed that the risk model could be used to predict the prognosis of HCC more accurately. The risk score also resulted as an independent risk factor for HCC prognosis (TCGA: HR = 2.45, 95% CI 1.53–3.92; ICGC: HR = 2.19, 95% CI 1.39–3.46). Moreover, the AUC of the risk score for diagnosing HCC was relatively higher (TCGA: AUC = 0.840, P < 0.05; ICGC: AUC = 0.795, P < 0.05).

Conclusions

In a word, BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC, GSDMD, and the pyroptosis-related risk model could be used to diagnose the HCC, and the risk score also resulted as an independent risk factor for the HCC prognosis.
Usefulness of echocardiographic myocardial work in evaluating the microvascular perfusion in STEMI patients after revascularization
Authors: Jin Wenying , Wang Lan , Zhu Tiangang , Ma Yuliang , Yu Chao , Zhang Feng
Published: May 2022

Background

Left ventricular myocardial work (MW) assessed by echocardiography has recently been introduced as a new index of global and regional myocardial performance. The presence of microvascular obstruction after revascularization in ST-segment elevation myocardial infarction (STEMI) patients predicts poor clinical outcomes. This study aimed to explore the usefulness of MW in identifying impaired microvascular perfusion (MVP) in the patients with STEMI after revascularization.

Methods

One hundred and sixty STEMI patients who underwent myocardial contrast echocardiography (MCE) within 48 h after percutaneous coronary intervention (PCI) were included. Patients were divided into normal MVP and impaired MVP groups according to the myocardial perfusion score. The clinical data, coronary angiography results and echocardiographic data including Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were collected.

Results

Impaired MVP was found in 60% of patients. Compared with the normal MVP group, GWI (909.2 ± 287.6 mmHg% vs. 1191.2 ± 378.2 mmHg%), GCW (1198.3 ± 339.6 mmHg% vs. 1525.9 ± 420.5 mmHg%), GWE (82.7 ± 7.8% vs. 86.8 ± 5.6%) and GLS (− 11.0 ± 3.4% vs. − 14.4 ± 3.8%) were significantly reduced in the impaired MVP group. Whereas there was no statistically significant difference in left ventricular ejection fraction (LVEF) and GWW, multivariate logistic regression analysis showed that peak troponin I (OR 1.017, 95% CI 1.006–1.029; P = 0.004), final TIMI flow ≤ 2 (OR 16.366, 95% CI 1.998–134.06; P = 0.009), left ventricular end-diastolic volume index (LVEDVi) (OR 1.139 95% CI 1.048–1.239; P = 0.002), and GWI (OR 0.997 95% CI 0.994–1.000; P = 0.029) were independently associated with impaired MVP. GWI showed a good sensitivity (86.8%) but low specificity (53.7%) in identifying impaired MVP (AUC 0.712, 95% CI 0.620–0.804; P < 0.001). Combination with GWI can improve the diagnostic value of TNI or LVEVi for impaired MVP.

Conclusion

Impaired MVP is relatively common in STEMI patients after revascularization and independently associated with left ventricular GWI assessed by echocardiography. GWI confer incremental value to MVP assessment in STEMI patients.
Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial
Authors: Wang Cunliang , Zhu Shouhui , Miao Chuanwang , Wang Yu , Chen Jiazhen , Yuan Shuanghu , Hu Xudong
Published: May 2022

Objective

To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC).

Methods

We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up.

Results

The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 109/L) on day 1 and peaked 6.81 ± 2.37 (× 109/L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 109/L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 109/L) on day 10 (P < 0.05). The experimental group had a lower FN incidence than the control group (P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time.

Conclusion

PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.
Do different foot types affect the 6-min walk test capacity of younths with Charcot-Marie-Tooth neuropathy ?
Authors: Rogean de Jesus Alves de Baptista Cyntia , Garcia Beatriz , Cardoso Juliana , Nascimento Elias Adriana , Parra Buzzetti Beatriz , Claudia Mattiello-Sverzut Ana
Published: May 2022

Background

The present study aimed to assess the gait capacity of youths with Charcot Marie Tooth disease (CMT), considering the different foot postures as a grouping variable. 

Methods

The total distance, the predicted distance, and gait velocity obtained during the six-minute walking test (6MWT) were compared between participants with and without CMT. In addition, part of the CMT group completed a 12-month follow-up. The study evaluated 63 participants (CMT group = 31; Non-CMT group = 32) aged 6 to 18, both sexes. Data included anthropometric measures, foot posture index (FPI), the distance (D6), percentage of predicted distance (%D6), and walking velocity(V) in 6MWT.

Results

The D6% presented no significant difference between the types of feet in CMT or Non-CMT (p < 0.05, Kruskal Wallis test). CMT presented reduced values of D6, %D6, and V when compared to Non-CMT.

Conclusions

These findings indicate that gait performance was decreased in youths with CMT in comparison to non-CMT. Contrary to what was expected, the cavus foot type did not show lower gait capacity than the flatfoot, suggesting that the types of feet alone did not determine differences in gait capacity within the CMT group
Birth weight influences differently on systolic and diastolic blood pressure in children and adolescents aged 8–15
Authors: Huang Rui , Yang Shengxiang , Lei Yuhua
Published: May 2022

Aim

Globally, hypertension is one of the main threats to public health and a significant risk factor predisposing individuals to various cardiovascular conditions. Hypertension in the young is particularly complex and challenging. Accumulating evidence has implicated that low birth weight is vital for elevated blood pressure, and birth weight was negatively correlated with blood pressure. However, fewer studies with conflicting results have addressed the associations between birth weight and blood pressure in children and adolescents, and there is no relevant research conducted in the NHANES population. The principal objective of this project was to investigate the relationship between birth weight and blood pressure in children and adolescents in NHANES.

Methods

A total of 7600 subjects aged 8 to15 were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Outcome variables were systolic blood pressure(SBP) and diastolic blood pressure(DBP). Birth weight was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were performed to examine the association between birth weight and SBP or DBP.

Results

Birth weight was negatively correlated with SBP in the fully-adjusted model(β = -0.02, 95%CI: -0.04 to -0.04, p = 0.0013), especially in non-Hispanic White (β = -0.03, 95%CI: -0.06 to -0.00,p = 0.0446), aged between 13 to 15(β = -0.03, 95%CI: -0.04 to -0.01, p = 0.0027), and male individuals(β = -0.03, 95%CI: -0.05 to -0.01, p = 0.0027). However, there was no unidirectional association between birth weight and DBP in the fully adjusted model(β = -0.01, 95%CI: -0.03 to 0.02, p = 0.5668) and in sub-analysis. An inverted U-shaped and J-shaped relationship was uncovered between birth weight and DBP in those aged 13 or above and Mexican Americans, respectively. The inflection point calculated by a recursive algorithm of birth weight in these groups was all 105 oz.

Conclusions

The current study identified that birth weight was negatively related to SBP but not significantly related to DBP in children and adolescents aged 8 to 15, highlighting different potential mechanisms behind high SBP and high DBP in the young. However, an inverted U-shaped and J-shaped relationship between birth weight and DBP was observed, suggesting that targeted intervention measures should be taken for different groups of people rather than generalizations.
Preventing male suicide through a psychosocial intervention that provides psychological support and tackles financial difficulties: a mixed method evaluation
Authors: Jackson Joni , Farr Michelle , Birnie Kate , Davies Philippa , Mamluk Loubaba , O’Brien Marina , Spencer Jez , Morgan Rebecca , Costello Christian , Smith John , Banks Jonathan , Redaniel Maria Theresa
Published: May 2022

Background

To help resolve high suicide rates in Bristol, North Somerset and South Gloucestershire, the charity Second Step was commissioned to roll-out the Hope service offering a psychosocial intervention for men, supporting them through acute distress and addressing financial difficulties. This study evaluated the impact of the Hope service on men at risk of suicide experiencing financial and other difficulties.

Methods

Mixed methods study using: (i) a prospective cohort study design to compare depression, suicidal ideation and financial self-efficacy scores of men aged 30–64, referred to the service between October 2018 and July 2020, at baseline and 6 months follow-up and between low and moderate to high-intensity service users; and (ii) a qualitative interview study to evaluate the acceptability and impact of the Hope service to Hope service users.

Results

There was a 49% reduction in depression score (mean reduction − 10.0, 95% CI − 11.7 to − 8.3) and in the proportion of service users with suicidal ideation (percent reduction − 52.5, 95% CI − 64.1% to − 40.9%) at 6 months follow-up compared to baseline. Financial self-efficacy scores increased by 26% (mean increase 2.9, 95% CI 1.8 to 3.9). Qualitative accounts illustrated how ‘Hope saved my life’ for several men interviewed; most respondents described being able to move forward and tackle challenges with more confidence following the Hope intervention. Professional advice to tackle financial and other difficulties such as housing helped to relieve anxiety and stress and enable practical issues to be resolved.

Conclusions

The Hope service offered practical and emotional support to men who have experienced suicidal feelings, redundancy, homelessness and poverty and occupies an important space between mental health and social care provision. Hope demonstrates the value of an intervention which cuts across traditional boundaries between psychiatric care and social advice agencies to provide, what is, in effect, an integrated care service.
Modeling the effects of physical activity, education, health, and subjective wealth on happiness based on Indonesian national survey data
Authors: Patria Bhina
Published: May 2022

Background

Studies on physical activity’s psychological benefits are generally fewer than those on its physiological benefits, and these limited studies have mostly investigated its impact on cognitive functions. Studies exclusively investigating physical activity’s effects on happiness are rare. This study aims to investigate the effect of physical activity on psychological functions, especially on happiness.

Methods

Analysis was based on a large field of nationally representative Indonesian adult data. Data were compiled based on face-to-face interviews with 12,051 adults. Participants provided measures of physical activity, subjective health, and happiness, and responses were recorded with computer-assisted personal interviewing (CAPI) software. Demographic data, including gender, subjective wealth, education, and age, were also included in the analysis. Structural equation modeling (SEM) was conducted to determine the relationship between physical activity, health, subjective wealth, and happiness.

Results

The tested model of the association between physical activity, health, subjective wealth, and happiness indicated a good fit, based on χ2 (1, n = 12,051) = 48.733, p = .001, RMSEA = .063, and CFI = .97. Path analysis results showed that health conditions mediated the effects of physical activity on happiness. The result also showed positive effects of education level and subjective wealth on happiness.

Conclusion

This study provides evidence that engagement in physical activity has a positive impact on happiness. Indonesian adults should engage in more active lifestyles since more than one-third of Indonesians did not get enough physical activity.
Food insecurity and SNAP use among sexual minority people: analysis of a population-based sample from National Health Interview Survey, 2017
Authors: Jabson Tree Jennifer M. , Russomanno Jennifer , Bartmess Marissa , Anderson Joel G.
Published: May 2022

Background

Food insecurity is a pressing public health problem. Lesbian, gay, and bisexual (LGB) people are at increased risk for food insecurity, yet this issue remains grossly understudied among this population. The purpose of this study was to add to the existing literature surrounding food insecurity and the use of federal food assistance programs (SNAP) among LGB people.

Methods

This study used publicly available, de-identified data from the 2017 National Health Interview Survey (NHIS). Primary variables were sexual orientation, food security status, and receipt of SNAP. Food security was assessed using the 10-item USDA Family Food Security measure.

Results

In our sample, people who identified as bisexual had the highest rates of food insecurity (23.8%, n = 76). Female sexual minorities were 52% more likely to experience food insecurity (aOR = 1.518, 95% CI 1.105–2.087, p = .01) and 44% more likely to report household SNAP assistance than their heterosexual counterparts (aOR = 1.441, 95% CI 1.025–2.028, p = .03). SNAP partially mediated the association between sexual orientation and food insecurity for LGB females.

Conclusions

Our findings add to the growing empirical evidence documenting food insecurities among sexual minority adults. Our results reiterate the need for sexual orientation to be included in nationally representative federal food security measures.
The progression of the vertebral body bruise associated with a spinal fracture
Authors: Kim Young-Woo , Moon Seong-Hwan , Koh Sung Hye , Tae Kim Ki , Yoon Won Yong , Lee Jeong Hwan , Kim Seonghyeon , Sung Paul S. , Park Moon Soo
Published: May 2022

Background

Advances in magnetic resonance imaging (MRI) have made it possible to find the vertebral body bruise (VBB), which was not found in computed tomography (CT) after trauma. There has been only one study with adult patients about whether traumatic VBB will cause a collapse of the vertebral body or not. The purpose is to elucidate the progression of VBB in non-osteoporotic adult patients and to identify the possible factors influencing the progression.

Method

The VBB was defined on MRI as band-like or diffuse zones of high signal intensity on T2-weighted sequences without fracture of the cortex based on CT. The study population with traumatic VBB associated with non-osteoporotic spinal fracture was composed of 15 females and 21 males. The minimal follow-up period was 6 months. The ratio of anterior to posterior heights of the VBB, the ratio of anterior heights of the VBB to the average of those of cranial and caudal adjacent vertebral bodies, the anterior wedge angle of the VBB, and the focal angle around the VBB were compared between the initial and final visits. We evaluated the age of the patients, the C2 plumb line distance, the regional location of VBB, the etiology of VBB, and the treatment methods of the fractures as possible risk factors influencing the progression.

Results

There was no difference in the ratios and angles between the initial and final visits. The differences in the ratios and angles between the initial and final visits were not dependent on the possible risk factors. The anterior superior area is the most common in the distribution of VBB.

Conclusions

Unlike compression fractures, the vertebral body with traumatic VBB found in adult patients with non-osteoporotic spinal fractures of AO classification A or B types did not develop collapse. In clinical practice, it is reasonable to diagnose it as a spinal fracture rather than a VBB if the collapse of a possible VBB occurs.
Changes in salivary matrix metalloproteinase-3, -8, and -9 concentrations after 6 weeks of non-surgical periodontal therapy
Authors: Kim Han-Na
Published: May 2022

Background

Studies using salivary inflammatory biomarkers for diagnosing and monitoring the progression of periodontal disease have garnered increased attention in recent years. The present study aimed to identify changes in clinical parameters and concentrations of salivary matrix metalloproteinases (MMPs) following 6 weeks of non-surgical periodontal therapy (NSPT).

Methods

A 6-week NSPT program was applied to 51 adults aged ≥ 20 years. The program involved scaling, root planing, and professional toothbrushing for healthy participants and those with periodontal disease. Patients with periodontal disease underwent professional toothbrushing during all three visits. Periodontal pocket depth (PD) and gingival bleeding were assessed at week 0, week 3, and week 6, and saliva samples were collected to measure the concentrations of MMP-3, -8, and -9.

Results

All clinical parameters were improved in the periodontal disease groups following the NSPT course. Compared with healthy participants, the patients with periodontal disease showed increased concentrations of salivary MMP-3, -8, and -9. During the 6-week program, patients with periodontal disease also showed significant reductions in PD and gingival bleeding during the third week; no significant reduction was found during the sixth week. Significant reductions in the concentrations of salivary MMP-3, -8, and -9 were also noted in the periodontal disease group at week 3. The sensitivity and specificity of MMP-3 for predicting periodontitis were 81.8% and 55.5%, respectively.

Conclusion

The present study found that NSPT resulted in reductions of salivary MMP-3, -8, and -9, and identified the potential of MMP-3 as a biomarker in the diagnosis of periodontal disease. These findings may serve as foundational data for future studies into the development of diagnostic kits for periodontal disease.
Improving access to medicines by popularising generics: a study of ‘India’s People’s Medicine’ scheme in two districts of Maharashtra
Authors: Lavtepatil Sonam , Ghosh Soumitra
Published: May 2022

Background

In spite of being the ‘pharmacy of the world’, access to essential medicines for a large majority of Indians is constrained by both physical and financial reasons. According to an estimate, medicines account for 69% of household out-of-pocket spending on health care. To make quality generic medicine affordable, India’s People’s Medicine Scheme (Jan Aushadhi) was launched in 2008 and then revamped and rebranded as Pradhan Mantri Bhartiya Jan Ausadhi Pariyojana (PMBJP) in 2015. The current study focuses on the availability, affordability and acceptability aspects of PMBJP essential medicines.

Methods

We have used a mixed-methods approach, with the survey-based quantitative component supplemented by a qualitative component consisting of in-depth interviews (IDIs). The survey was conducted in 11 PMBJP pharmacies in Mumbai and Palghar. Data were gathered on the availability, stock-outs, price and affordability of 35 essential medicines and 2 consumables.

Results

Apart from the limited coverage of essential medicines and the significant presence of Fixed dose combinations (FDCs) in the PMBJP medicine list, the availability of surveyed essential drugs was also found to be low (47%) in PMBJP outlets. Across Mumbai and Palghar districts, around 50% and 42% of medicines were found to be out of stock for the period of 3–6 months respectively. The cost of generic medicines of PMBJP outlets for treating various conditions range from 0.01 days’ wages to 0.47 days’ wages for the lowest paid unskilled worker in Maharashtra.

Conclusions

The study findings show that PMBJP’s unbranded generics offer great opportunities for substantial cost savings. But, in order to fully realise the potential of this scheme, some policy actions are urgently required. First, the PMBJP drug list must include all essential drugs that feature in NLEM. Second, BPPI should procure only those drugs that pass the bioequivalence test. Third, compulsory de-branding of generics should be done in a phased manner. Fourth, PMBJP’s medicine procurement and distribution policies must be reviewed to address the supply chain issues. Moreover, there is a need for major pharmaceutical policy reforms to promote generic medicines in a big way. Regulations to support mandatory generic prescribing and generic substitution by pharmacists are needed.
Roles of airway basal stem cells in lung homeostasis and regenerative medicine
Authors: Wu Meirong , Zhang Xiaojing , Lin Yijian , Zeng Yiming
Published: May 2022

Airway basal stem cells (BSCs) in the proximal airways are recognized as resident stem cells capable of self-renewing and differentiating to virtually every pseudostratified epithelium cell type under steady-state and after acute injury. In homeostasis, BSCs typically maintain a quiescent state. However, when exposed to acute injuries by either physical insults, chemical damage, or pathogen infection, the remaining BSCs increase their proliferation rate apace within the first 24 h and differentiate to restore lung homeostasis. Given the progenitor property of airway BSCs, it is attractive to research their biological characteristics and how they maintain homeostatic airway structure and respond to injury. In this review, we focus on the roles of BSCs in lung homeostasis and regeneration, detail the research progress in the characteristics of airway BSCs, the cellular and molecular signaling communications involved in BSCs-related airway repair and regeneration, and further discuss the in vitro models for airway BSC propagation and their applications in lung regenerative medicine therapy.
Lifetime ovulatory years and ovarian cancer gene expression profiles
Authors: Sasamoto Naoko , Stewart Paul A. , Wang Tianyi , Yoder Sean J. , Chellappan Srikumar , Hecht Jonathan L. , Fridley Brooke L. , Terry Kathryn L. , Tworoger Shelley S.
Published: May 2022

Background

Greater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways.

Methods

RNA sequencing data was generated on 234 invasive ovarian cancer tumors that were high-grade serous, poorly differentiated, or high-grade endometrioid from the Nurses’ Health Study (NHS), NHSII, and the New England Case Control Study. We used linear regression to identify differentially expressed genes by estimated ovulatory years, adjusted for birth decade and cohort, overall and stratified by menopausal status at diagnosis. We used false discovery rates (FDR) to account for multiple testing. Gene set enrichment analysis (GSEA) with Cancer Hallmarks, KEGG, and Reactome databases was used to identify biological pathways associated with ovulatory years.

Results

No individual genes were significantly differentially expressed by ovulatory years (FDR > 0.19). However, GSEA identified several pathways that were significantly associated with ovulatory years, including downregulation of pathways related to inflammation and proliferation (FDR < 1.0 × 10–5). Greater ovulatory years were more strongly associated with downregulation of genes related to proliferation (e.g., E2F targets, FDR = 1.53 × 10–24; G2M checkpoints, FDR = 3.50 × 10–22) among premenopausal versus postmenopausal women at diagnosis. The association of greater ovulatory years with downregulation of genes involved in inflammatory response such as interferon gamma response pathways (FDR = 7.81 × 10–17) was stronger in postmenopausal women.

Conclusions

Our results provide novel insight into the biological pathways that link ovulatory years to ovarian carcinogenesis, which may lead to development of targeted prevention strategies for ovarian cancer.
Patient-individualized resection planning in liver surgery using 3D print and virtual reality (i-LiVR)—a study protocol for a prospective randomized controlled trial
Authors: Huber Tobias , Hanke Laura Isabel , Boedecker Christian , Vradelis Lukas , Baumgart Janine , Heinrich Stefan , Bartsch Fabian , Mittler Jens , Schulze Alicia , Hansen Christian , Hüttl Florentine , Lang Hauke
Published: May 2022

Background

A multitude of different diseases—benign and malign—can require surgery of the liver. The liver is an especially challenging organ for resection planning due to its unique and interindividually variable anatomy. This demands a high amount of mental imagination from the surgeon in order to plan accordingly - a skill, which takes years of training to acquire and which is difficult to teach. Since the volume of the functional remnant liver is of great importance, parenchyma sparing resections are favoured. 3D reconstructions of computed tomography imaging enable a more precise understanding of anatomy and facilitate resection planning. The modality of presentation of these 3D models ranges from 2D monitors to 3D prints and virtual reality applications.

Methods

The presented trial compares three different modes of demonstration of a 3D reconstruction of CT scans of the liver, which are 3D print, a demonstration on a regular computer screen or using a head-mounted virtual reality headset, with the current gold standard of viewing the CT scan on a computer screen. The group size was calculated with n=25 each. Patients with major liver resections in a laparoscopic or open fashion are eligible for inclusion. Main endpoint is the comparison of the quotient between planned resection volume and actual resection volume between these groups. Secondary endpoints include usability for the surgical team as well as patient specifics and perioperative outcome measures and teaching issues.

Discussion

The described study will give insight in systematic planning of liver resections and the comparison of different demonstration modalities of 3D reconstruction of preoperative CT scans and the preference of technology. Especially teaching of these demanding operations is underrepresented in prior investigations.

Trial registration

Prospective trials registration at the German Clinical Trials register with the registration number DRKS00027865. Registration Date: January 24, 2022.
Optimization of extraction process parameters of caffeic acid from microalgae by supercritical carbon dioxide green technology
Authors: Pyne Smritikana , Paria Kishalay
Published: May 2022

Purpose

In this study, the optimization of extraction process parameters of caffeic acid content from Spirulina platensis is performed by supercritical green technology.

Methods

Especially, the optimization of supercritical carbon dioxide (SC-CO2) extraction parameters was carried out employing Box-Behnken design (BBD) and response surface methodology (RSM). Alongside, the three levels of extraction parameters i.e. extraction pressure, extraction time and temperature have been fixed. As a response, the caffeic acid content of the extracts was determined by HPLC. The statistical analysis (ANOVA) of developed mathematical models was used in the process.

Results

The extract exhibited the highest content of caffeic acid as 72.11 µg/g of dw at the optimized extraction conditions of 360.08 bar pressure for 57.13 min extraction time at 38.31 °C temperature. Simultaneously this extract exhibited the highest content of total phenolic content (76.87 µg GAE/g dw), reducing power (2278 µg BHT/g dw), FRAP value (4.19 mM FeSO4 equivalent/g dw) and IC50 for DPPH activity (89.28 µg/mL).

Conclusion

It has been also noted that supercritical fluid extract can significantly retard the growth of microorganisms in litchi beverage. Consequently, we can also predict that isolated SC-CO2 antioxidant containing fraction would have hopeful for foodstuff preservative.
The effect of expertise on postural control in elite sport ju-jitsu athletes
Authors: Akbaş Anna , Marszałek Wojciech , Drozd Sławomir , Czarny Wojciech , Król Paweł , Warchoł Krzysztof , Słomka Kajetan J. , Rzepko Marian
Published: May 2022

Background

Due to the high postural control demands of sport ju-jitsu, it is likely that long-term sport ju-jitsu training may induce sport-specific adaptations in postural control, especially in positions directly related to combat. The aim of the study was to assess the differences in postural control between elite sport ju-jitsu athletes and untrained controls in non-ecological and ecological conditions and to investigate the relative contribution of spinal and supraspinal mechanisms to postural control in expert athletes.

Methods

The study was conducted on eleven male elite ju-jitsu athletes and ten non-athletes. The data was collected with the use of a force plate under two conditions: quiet standing and ju-jitsu combat stance. Apart from the standard analysis of the spatial–temporal parameters of center of foot pressure, non-linear measures were used, namely rambling-trembling and sample entropy. The non-parametric Mann–Whitney U test was used to compare both groups.

Results

The main findings of the study showed that in quiet standing, elite ju-jitsu athletes and non-athletes had comparable postural control in both the anterior–posterior and mediolateral planes. In contrast, in the combat stance, elite athletes had lower values of postural sway and rambling component (range and rms) and higher values of sample entropy in comparison to the non-athletes (p < 0.05). No differences were found in the trembling component of sway between groups in the combat stance (p < 0.05).

Conclusions

Smaller postural sway and its rambling component in sport ju-jitsu athletes may indicate the more precise control of center of foot pressure and improved ability in estimating its position. The sample entropy results confirmed that the displacement of center of foot pressure for sport ju-jitsu athletes was more irregular, which demonstrates greater automatization in postural control. The results also confirm the importance of ecological validity in investigating postural adaptations associated with sports expertise.
Strain-dependent motility defects and suppression by a flhO mutation for B. subtilis bactofilins
Authors: Holtrup Sven , Graumann Peter L.
Published: May 2022

Objective

Bactofilins can assemble into polymeric structures and play important roles in cell shape maintenance, chromosome segregation and motility. Bacillus subtilis bactofilins BacE and BacF were shown to be important for swimming motility in strain PY79, and single gene deletions were reported to be lethal, in contrast to a double bacEF deletion.

Results

Extending this work, we show that motility defects vary between different B. subtilis strains, with strain 168 showing no defect in motility, and 3610 showing delayed induction of swimming. Generation of single gene deletions in PY79 was possible by transferring corresponding deletions from 168. In the natural isolate 3610, gene deletions also showed a negative effect on biofilm formation, revealing an additional function for BacE and BacF. A spontaneous arising suppressor mutation in PY79 was mapped to the flhO gene, a constituent of the flagellum, which obtained an 18 amino acid extension at its C-terminus. Our findings show that bactofilin gene deletions lead to different motility phenotypes dependent on the strain background, and affect biofilm formation in the natural isolate 3610. Our data reinforce the idea of a connection between bactofilins and motion via the flagellum, and suggest that they operate in a switch like manner.
Development of a quantitative methylation-specific droplet digital PCR assay for detecting Dickkopf-related protein 3
Authors: Araki Kenji , Kurosawa Ai , Kumon Hiromi
Published: May 2022

Objective

The detection and monitoring of DNA methylation status in circulating tumor cell DNA (ctDNA) provides critical insights into cancer diagnosis and progression. The methylation status of the Dickkopf-related protein 3 (DKK3) promoter region is correlated with the metastasis and recurrence of multiple cancers. Thus, detecting the methylation status via non-invasive methods is essential for the diagnosis and prognosis of cancers. Using a droplet digital polymerase chain reaction approach, we have developed a highly sensitive and quantitative measurement of methylated and unmethylated DKK3 derived from circulating cell-free DNA (ccfDNA).

Results

We confirmed the specificity of droplet digital methylation specific polymerase chain reaction (ddMSP). We selected the optimal bisulfite conversion method using commercially available kits. We validated the ddMSP analysis system by analyzing the methylation status of genomic DNA extracted from cultured mesothelioma cells and mesothelial cells. Our system quantified approximately 30 copies of cell-free DNA per 4 mL, which is sufficient for detecting ctDNA. Finally, we quantified methylated and unmethylated DKK3 copies in ccfDNA from 21 patients with malignant mesothelioma.
Elucidating the role of the gut microbiota in the physiological effects of dietary fiber
Authors: Deehan Edward C. , Zhang Zhengxiao , Riva Alessandra , Armet Anissa M. , Perez-Muñoz Maria Elisa , Nguyen Nguyen K. , Krysa Jacqueline A. , Seethaler Benjamin , Zhao Yuan-Yuan , Cole Janis , Li Fuyong , Hausmann Bela , Spittler Andreas , Nazare Julie-Anne , Delzenne Nathalie M. , Curtis Jonathan M. , Wismer Wendy V. , Proctor Spencer D. , Bakal Jeffrey A. , Bischoff Stephan C. , Knights Dan , Field Catherine J. , Berry David , Prado Carla M. , Walter Jens
Published: May 2022

Background

Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25–35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX;n= 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC;n= 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamineN-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers.

Results

AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC.

Conclusion

This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization.

Trial registration

Clinicaltrials.gov,NCT02322112, registered on July 3, 2015.