bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Epidural and Subgaleal Abscesses in Pediatric Craniosynostosis Surgery
Authors: Arslan Muhammad , Smola Cassi , Soto Edgar , Rahman AKM F. , Grant John H. , Johnston James M.
Published: May 2023

Introduction:

Epidural/subgaleal abscesses in craniosynostosis surgery are rare but serious complications that may compromise neurological functioning in pediatric craniofacial populations. We evaluated the risk and evolution of management of post-operative subgaleal/epidural abscesses in craniosynostosis patients treated over 20 years by a single surgeon.

Methods:

Pediatric patients who underwent transcranial procedures for craniosynostosis by a single surgeon from 1997 to 2018 were included. The patients were stratified into groups based on the development of post-op abscess. The primary outcome measure was bone salvage success. Post-op abscesses were drained in the following manner: either open packing with delayed closure or no elevation of the scalp flap, followed by copious irrigation and deep (epidural) drain placement plus long-term intravenous antibiotics.

Results:

A total of 384 patients underwent 413 cases in this period: 177 sagittal, 85 unicoronal, 49 metopic, 4 lambdoid, and 69 cases of multiple suture synostosis. In this cohort, epidural/subgaleal abscess were found in 6 patients (1.5%) who all had bilateral fronto-orbital advancement ( P = .03). Bone salvage was attempted in all 6 patients with only minor bone resorption seen in 3 of the patients who presented with abscess.

Conclusion:

This study found that patients undergoing bilateral fronto-orbital advancement were at increased risk of a deep space infections, while those undergoing clavarial vault remodeling with barrel staves alone, were not. We were able to salvage the bone grafts and prevent neurological sequela with surgical washout, placement of drains and intravenous antibiotic therapy.
Vrančiceite, Cu10Hg3S8, a new Cu–Hg sulfide mineral from Vrančice, Czech Republic
Authors: Sejkora Jiří , Biagioni Cristian , Škácha Pavel , Mauro Daniela
Published: May 2023

Vrančiceite is a new mineral species discovered in a sample collected from the old mine dumps of the abandoned Vrančice deposit near Příbram, central Bohemia, Czech Republic. Vrančiceite occurs as rare anhedral grains, up to 100 μm in size, in a calcite gangue, associated with cinnabar, djurleite, galena and hedyphane. Vrančiceite is black, with metallic lustre. Mohs hardness is ca. 2–3, calculated density is 6.652 g.cm–3. In reflected light, vrančiceite is light grey with a yellowish shade; bireflectance, pleochroism and anisotropy are all weak. Internal reflections were not observed. Reflectance values for the four Commission on Ore Mineralogy wavelengths of vrančiceite in air [Rmax, Rmin (%) (λ in nm)] are: 33.6, 31.2 (470); 33.9, 30.6 (546); 31.1, 30.0 (589); and 32.1, 29.1 (650). The empirical formula, based on electron-microprobe analyses, is Cu10.11(4)Ag0.01(1)Hg2.87(4)Sb0.01(1)Bi0.01(1)S7.99(8). The ideal formula is Cu10Hg3S8 (Z = 2), which requires (in wt.%) Cu 42.54, Hg 40.29 and S 17.17, total 100.00. Vrančiceite is triclinic, P$\bar{1}$, with unit-cell parameters a = 7.9681(2), b = 9.7452(3), c = 10.0710(3) Å, α = 77.759(1), β = 76.990(1), γ = 79.422(1)°, V = 737.01(4) Å3 and Z = 2. The strongest reflections of the calculated powder X-ray diffraction pattern [d, Å (I) hkl] are: 3.354 (76) $\bar{2}$01, 3.111 (68) 222, 2.833 (100) 213, 2.733 (93) 231, 2.705 (76) 2$\bar{2}$1 and 2.647 (71) $\bar{2}\bar{1}$2. According to the single-crystal X-ray diffraction data (R1 = 0.0262), the crystal structure of vrančiceite can be described as comprising Cu–S layers, connected through CuS3 polyhedra, giving rise to a three-dimensional framework with channels running along the a axis and hosting linearly coordinated Hg atoms. Structural relations with gortdrumite are discussed. Vrančiceite is named after its type locality, the Vrančice deposit near Příbram. The mineral and its name have been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA2022–114).
Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias
Authors: Fierro-Pineda Juan C. , Tsai Hua-Ling , Blackford Amanda , Cluster Andrew , Caywood Emi , Dalal Jignesh , Davis Jeffrey , Egeler Maarten , Huo Jeffrey , Hudspeth Michelle , Keating Amy , Kelly Susan S. , Krueger Joerg , Lee Dean , Lehmann Leslie , Madden Lisa , Oshrine Benjamin , Pulsipher Michael A. , Fry Terry , Symons Heather J.
Published: May 2023

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) at 180 days was 0%. The cumulative incidence (CuI) of grade 2 acute graft-versus-host disease (aGVHD) on day 100 was 13%. No patients developed grades 3-4 aGVHD. The CuI of moderate-to-severe chronic GVHD (cGVHD) at 1 year was 4%. Donor engraftment occurred in 27 patients (84%). Primary graft failures included 3 patients who received suboptimal bone marrow grafts; all successfully engrafted after second transplants. The CuI of relapse at 1 year was 32%, with more relapse among patients MRD positive pre-BMT vs MRD negative. Overall survival rates at 1 and 2 years were 77% and 73%, and event-free survival rate at 1 and 2 years were 68% and 64%. There was no TRM or severe aGVHD, low cGVHD, and favorable relapse and survival rates. This successful pilot trial has led to a phase 3 trial comparing MAC haploBMT vs HLA-matched unrelated donor BMT in the Children’s Oncology Group. This trial was registered at www.clinicaltrials.gov as #NCT02120157.
An Fc-muted bispecific antibody targeting PD-L1 and 4-1BB induces antitumor immune activity in colorectal cancer without systemic toxicity
Authors: Cheng Lian-sheng , Zhu Min , Gao Yan , Liu Wen-ting , Yin Wu , Zhou Pengfei , Zhu Zhongliang , Niu Liwen , Zeng Xiaoli , Zhang Dayan , Fang Qing , Wang Fengrong , Zhao Qun , Zhang Yan , Shen Guodong
Published: May 2023

Background

Resistance to immune checkpoint inhibitor (ICI) therapy narrows the efficacy of cancer immunotherapy. Although 4-1BB is a promising drug target as a costimulatory molecule of immune cells, no 4-1BB agonist has been given clinical approval because of severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods

HK010 was generated by antibody engineering, and the Fab/antigen complex structure was analyzed using crystallography. The affinity and activity of HK010 were detected by multiple in vitro bioassays, including enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), flow cytometry, and luciferase-reporter assays. Humanized mice bearing human PD-L1-expressing MC38 (MC38/hPDL1) or CT26 (CT26/hPDL1) tumor transplants were established to assess the in vivo antitumor activity of HK010. The pharmacokinetics (PK) and toxicity of HK010 were evaluated in cynomolgus monkeys.

Results

HK010 was generated as an Fc-muted immunoglobulin (Ig)G4 PD-L1x4-1BB bispecific antibody (BsAb) with a distinguished Fab/antigen complex structure, and maintained a high affinity for human PD-L1 (KD: 2.27 nM) and low affinity for human 4-1BB (KD: 493 nM) to achieve potent PD-1/PD-L1 blockade and appropriate 4-1BB agonism. HK010 exhibited synergistic antitumor activity by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously, and being strictly dependent on the PD-L1 receptor in vitro and in vivo. In particular, when the dose was decreased to 0.3 mg/kg, HK010 still showed a strong antitumor effect in a humanized mouse model bearing MC38/hPDL1 tumors. Strikingly, HK010 treatment enhanced antitumor immunity and induced durable antigen-specific immune memory to prevent rechallenged tumor growth by recruiting CD8+ T cells and other lymphocytes into tumor tissue and activating tumor-infiltrating lymphocytes. Moreover, HK010 not only did not induce nonspecific production of proinflammatory cytokines but was also observed to be well tolerated in cynomolgus monkeys in 5 week repeated-dose (5, 15, or 50 mg/kg) and single-dose (75 or 150 mg/kg) toxicity studies.

Conclusion

We generated an Fc-muted anti-PD-L1x4-1BB BsAb, HK010, with a distinguished structural interaction with PD-L1 and 4-1BB that exhibits a synergistic antitumor effect by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously. It is strictly dependent on the PD-L1 receptor with no systemic toxicity, which may offer a new option for cancer immunotherapy.
Utility of urinary presepsin in the diagnosis of pyelonephritis: a cross-sectional study
Authors: Yamashita Ryo , Izumi Yusuke , Nakada Koji , Hiramoto Jun
Published: May 2023

Background

Presepsin is produced during the phagocytosis of bacteria by granulocytes. Presepsin increases at the site of infection; however, the significance of urinary presepsin in pyelonephritis is unknown. This study aimed to evaluate whether measuring urinary presepsin can distinguish between pyelonephritis and nonpyelonephritis.

Methods

A cross-sectional study of patients with suspected pyelonephritis was conducted. Urinary presepsin at admission was compared between the pyelonephritis and nonpyelonephritis groups using the Mann–Whitney test. The predictive accuracy of urinary presepsin for diagnosing pyelonephritis was evaluated by the area under the receiver operating characteristics (ROC) analysis curve.

Results

A total of 35 eligible participants were included in the pyelonephritis group and 25 in the nonpyelonephritis group. The median urinary presepsin level was 2232.0 (interquartile range [IQR], 1029.0–3907.0) pg/mL in the pyelonephritis group and 1348.0 (IQR, 614.5–2304.8) pg/mL in the nonpyelonephritis group. Urinary presepsin concentrations were significantly higher in the pyelonephritis group than in the nonpyelonephritis group (P = 0.023). ROC analysis of urinary presepsin revealed a cutoff value of 3650 pg/mL to distinguish between the pyelonephritis and nonpyelonephritis groups. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for the diagnosis of pyelonephritis were 0.40 (95% confidence interval [CI], 0.24–0.58), 0.96 (95% CI, 0.79–1.00), 0.93 (95% CI, 0.68–1.00), 0.52 (95% CI, 0.37–0.68), 9.60 (95% CI, 1.35–68.23), and 0.62 (95% CI, 0.47–0.83), respectively.

Conclusions

The measurement of urinary presepsin is useful in differentiating pyelonephritis from other diseases.
Correlation between overall survival and quality of life in colon cancer patients with chemotherapy
Authors: Murakawa Yasuko , Ootsuka Kazunori , Kusaka Jun , Miura Kou
Published: May 2023

Background

Patients presenting with inoperable colon cancer at first onset (ICF) or at time of relapse (ICR) are considered in unrecoverable. The therapeutic goal for unrecoverable cancer is to prolong overall survival (OS) and maintain a high quality of life (QOL). As data on objective indicators of QOL in cancer patients, such as length of hospitalisation (LOH), outpatient consultation times (OCT), and hospital-free survival (HFS), is limited, this study compared ICF and ICR with respect to OS and QOL over the entire clinical course.

Methods

We retrospectively evaluated 90 inoperable colon cancer patients with chemotherapy and compared ICF and ICR in terms of OS, LOH, OCT, and HFS.

Results

Patients with ICF had a worse OS than those with ICR. In patients with ICF and ICR, OS and LOH were not correlated but OS and OCT and OS and HFS were strongly correlated. In patients with ICF and ICR, OCT and HFS accounted for approximately 8% and 90% of their OS, respectively.

Conclusions

The LOH, OCT, and HFS are important factors for evaluating objective QOL of patients with inoperable colon cancer and should be considered when making treatment decisions.
A novel predictive model for phthisis bulbi following facial hyaluronic acid cosmetic injection
Authors: Si Shancheng , Su Wei , Wang Lei , Ji Yicong , Chen Anming , Hu Yuntao
Published: May 2023

Purpose

To observe long-term prognosis of anterior segment ischemia (ASI) following hyaluronic acid (HA) injection, propose a severity grading system for ASI and a predictive model for phthisis bulbi (PB) based on long-term secretion dysfunction of ciliary process.

Methods

This is a retrospective case–control study. All enrolled 20 patients were divided into two groups and followed for at least 6 months to observe the formation and transformation characteristics of ASI and long-term prognosis based on the degrees of ciliary function damage.

Results

The severity of ASI following HA injection could be subdivided into 4 grades according to the degrees of ciliary function damage, comprising ASI grades 0, 1, 2 and 3. In 20 patients, ophthalmoplegia at 1-month follow-up, ASI within 1 month, ASI at 1-month follow-up, hypotony within 6 months were all significantly more common in study group than in control group (60% vs. 0%, P = 0.011; 100% vs. 20%, P = 0.001; 100% vs. 0%, P < 0.001; 80% vs. 0%, P = 0.001, respectively). Sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) for predicting subsequent PB at 2-year follow-up through the co-occurrence of ophthalmoplegia at 1-month follow-up and hypotony within 6 months was 100%, 100% and 1.00, respectively.

Conclusions

The new grading system for ASI and novel predictive model for PB we proposed could predict the long-term prognosis and probability of subsequent PB due to ASI following HA injection through several dynamic assessments within 6 months.

Level of Evidence

Level IV, observational prognostic study.
Vaccination against influenza in pregnant women in a maternity hospital in the Czech Republic in the season 2020–2021
Authors: Kynčl Jan , Liptáková Monika , Košťálová Jana , Malý Marek , Křížová Marcela , Heřman Hynek , Fabiánová Kateřina
Published: May 2023

Objectives

Pregnant women are among the priority groups to receive influenza vaccines in the Czech Republic since 2011, data on vaccination coverage are not yet available. The aim of the study was to determine the influenza vaccination coverage (IVC) and provide source data for further activities.

Methods

A prospective observational study was performed in a large maternity hospital in Prague. The self-completed questionnaire was distributed to 5,475 pregnant women between September 1, 2020 and August 31, 2021. Questions included maternal sociodemographic characteristics, influenza vaccination status and sources of maternal vaccination recommendations during pregnancy.

Results

A total of 4,617 completed questionnaires have been analysed. The median age of study participants (N = 4,592) was 33 years (range: 18–51 years). The majority (69.7%) of women had completed their university education, most women were childless (58.5%) or had one child (32.5%) before the start of the study. Less than 2% of women reported being vaccinated against influenza during their pregnancy (1.5%; 95% CI, 1.1–1.9%). Only 21% of women knew that it’s possible to get vaccinated against influenza during pregnancy. Participants considered influenza vaccination in pregnancy as important (3.3%), useful (41.1%) and useless (44.4%). Out of 959 pregnant women who had information about influenza vaccination during pregnancy, only 6.9% were vaccinated, while among those who did not have this information, 0.1% were vaccinated during pregnancy (p < 0.001). The most frequent source of information was Internet, then media and a general practitioner.

Conclusions

The IVC during pregnancy in our study was extremely low. In order to improve IVC among pregnant women, it is necessary to increase awareness of recommendations and vaccination options among the public and professionals and incorporating vaccination recommendation in routine antenatal practice.
Thematic analysis of national online narratives on regular asymptomatic testing for Covid-19 in schools in England
Authors: Taylor-Egbeyemi Jo , Carter Holly , Robin Charlotte
Published: May 2023

Objective

To understand the public perceptions of the schools Covid-19 testing programme in England.

Design

Qualitative social media analysis.

Setting

Online users of parenting forums (Mumsnet and Netmums), Facebook newspaper pages and Daily Mail online readers, who responded to posts or articles about the schools testing programme in England, between 1 and 31 March, 2021.

Results

Overall, seven main themes were identified, these were divided into barriers and facilitators to engaging in testing for Covid-19. Barriers were: uncertainty around testing in the absence of symptoms; concerns about testing; implications about testing positive; mistrust in the Government. Facilitators were: desire to protect others; desire to return to normality; and hearing others’ positive experiences.

Conclusions

Our analysis highlighted that alongside well-established barriers to engaging in asymptomatic testing, parents were having to negotiate additional complex decisions around balancing their child’s anxiety over testing alongside acknowledgement of the implications of regular testing, such as return to normality and protecting others. Parents and children would benefit from additional practical and social support to facilitate engagement with the schools testing programme.
Dysbiosis of the intestinal fungal microbiota increases lung resident group 2 innate lymphoid cells and is associated with enhanced asthma severity in mice and humans
Authors: Kanj Amjad N. , Kottom Theodore J. , Schaefbauer Kyle J. , Choudhury Malay , Limper Andrew H. , Skalski Joseph H.
Published: May 2023

Background

The gut-lung axis is the concept that alterations of gut microbiota communities can influence immune function in the lungs. While studies have explored the relationship between intestinal bacterial dysbiosis and asthma development, less is understood about the impact of commensal intestinal fungi on asthma severity and control and underlying mechanisms by which this occurs.

Methods

Wild-type mice were treated with Cefoperazone to deplete gut bacteria and administered Candida albicans or water through gavage. Mice were then sensitized to house dust mite (HDM) and their lungs were analyzed for changes in immune response. Humans with asthma were recruited and stool samples were analyzed for Candida abundance and associations with asthma severity and control.

Results

Mice with intestinal Candida dysbiosis had enhanced Th2 response after airway sensitization with HDM, manifesting with greater total white cell and eosinophil counts in the airway, and total IgE concentrations in the serum. Group 2 innate lymphoid cells (ILC2) were more abundant in the lungs of mice with Candida gut dysbiosis, even when not sensitized to HDM, suggesting that ILC2 may be important mediators of the enhanced Th2 response. These effects occurred with no detectable increased Candida in the lung by culture or rtPCR suggesting gut-lung axis interactions were responsible. In humans with asthma, enhanced intestinal Candida burden was associated with the risk of severe asthma exacerbation in the past year, independent of systemic antibiotic and glucocorticoid use.

Conclusions

Candida gut dysbiosis may worsen asthma control and enhance allergic airway inflammation, potentially mediated by ILC2. Further studies are necessary to examine whether microbial dysbiosis can drive difficult-to-control asthma in humans and to better understand the underlying mechanisms.
A novel ROS-Related chemiluminescent semiconducting polymer nanoplatform for acute pancreatitis early diagnosis and severity assessment
Authors: Li Yuhang , Yin Baoli , Song Yinghui , Chen Kang , Chen Xu , Zhang Yujing , Yu Nanhui , Peng Chuang , Zhang XiaoBing , Song Guosheng , Liu Sulai
Published: May 2023

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future.
Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study
Authors: Gu Yifei , Jin Qianmei , Hu Jinquan , Wang Xinwei , Yu Wenchao , Wang Zhanchao , Wang Chen , Liu Yang , Chen Yu , Yuan Wen
Published: May 2023

Background

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility.

Methods

A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software.

Results

In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis.

Conclusion

The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.
Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2
Authors: Chen Cong , Wang Jie , Liu Yong-Mei , Hu Jun
Published: May 2023

Background

The distribution of ACE2 and accessory proteases (ANAD17 and CTSL) in cardiovascular tissue and the host cell receptor binding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial to understanding the virus’s cell invasion, which may play a significant role in determining the viral tropism and its clinical manifestations.

Methods

We conducted a comprehensive analysis of the cell type-specific expression of ACE2, ADAM17, and CTSL in myocardial tissue from 10 patients using RNA sequencing. Our study included a meta-analysis of 2 heart single-cell RNA-sequencing studies with a total of 90,024 cells from 250 heart samples of 10 individuals. We used co-expression analysis to locate specific cell types that SARS-CoV-2 may invade.

Results

Our results revealed cell-type specific associations between male gender and the expression levels of ACE2, ADAM17, and CTSL, including pericytes and fibroblasts. AGT, CALM3, PCSK5, NRP1, and LMAN were identified as potential accessory proteases that might facilitate viral invasion. Enrichment analysis highlighted the extracellular matrix interaction pathway, adherent plaque pathway, vascular smooth muscle contraction inflammatory response, and oxidative stress as potential immune pathways involved in viral infection, providing potential molecular targets for therapeutic intervention. We also found specific high expression of IFITM3 and AGT in pericytes and differences in the IFN-II signaling pathway and PAR signaling pathway in fibroblasts from different cardiovascular comorbidities.

Conclusions

Our data indicated possible high-risk groups for COVID-19 and provided emerging avenues for future investigations of its pathogenesis.

Trial registration

(Not applicable).
Differences between leukemic arthritis and juvenile idiopathic arthritis
Authors: Torres Jimenez Alfonso Ragnar , Solis Vallejo Eunice , Cespedes Cruz Adriana Ivonne , Ramirez Miramontes Julia Veronica , Cortina Olvera Guadalupe del Consuelo , Velazquez Cruz Alejandra , Sanchez Jara Berenice
Published: May 2023

Objectives

To determine the clinical and laboratory differences between leukemic arthritis (LA) and juvenile idiopathic arthritis (JIA) at the onset of the disease.

Material and methods

Patients under 16 years of age, both genders, who presented for the first time to the pediatric rheumatology service with a diagnosis of probable JIA, with arthritis and without peripheral blood blasts, in which the final diagnosis was acute lymphoblastic leukemia (ALL) or JIA. The clinical and laboratory characteristics of the patients were compared, chi-square and relative risk were used for categorical variables, and the Mann–Whitney U and T-test for the comparison of means between groups. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA.

Results

A total of 76 patients, 14 with LA and 62 with JIA, were analyzed. The mean age at diagnosis was lower in the leukemic arthritis group, the female gender prevailed in the JIA group, and the time to onset of symptoms was lower in the leukemic arthritis group. Patients with leukemic arthritis showed increased pain intensity, fever, weight loss, nocturnal diaphoresis, lymph node enlargement, hepatosplenomegaly, and pain that did not improve with analgesic administration. Laboratory parameters with statistical significance were the presence of anemia, leukopenia, and neutropenia. The platelet count was significant but in a low normal value, compared to the JIA. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. The probability associated with the statistic (Chi-square) was 0.000, and the Cox and Snell R2 and Nagelkerke R2 values were 0.615 and 1, respectively. The developed model correctly classified 100% of the cases.

Conclusions

The diagnosis of acute lymphoblastic leukemia should be ruled out in patients who present with arthritis and hematological alterations, mainly leukopenia and neutropenia, with joint pain disproportionate to the degree of arthritis, predominantly at night and that does not improve with the use of analgesics, fever, lymph nodes, and hepatosplenomegaly. Criteria are suggested to differentiate both diseases.
B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells
Authors: Dwyer Liam J. , Maheshwari Saumya , Levy Emily , Poznansky Mark C. , Whalen Michael J. , Sîrbulescu Ruxandra F.
Published: May 2023

Traumatic brain injury (TBI) remains a major cause of death and severe disability worldwide. We found previously that treatment with exogenous naïve B cells was associated with structural and functional neuroprotection after TBI. Here, we used a mouse model of unilateral controlled cortical contusion TBI to investigate cellular mechanisms of immunomodulation associated with intraparenchymal delivery of mature naïve B lymphocytes at the time of injury. Exogenous B cells showed a complex time-dependent response in the injury microenvironment, including significantly increased expression of IL-10, IL-35, and TGFβ, but also IL-2, IL-6, and TNFα. After 10 days in situ, B cell subsets expressing IL-10 or TGFβ dominated. Immune infiltration into the injury predominantly comprised myeloid cells, and B cell treatment did not alter overall numbers of infiltrating cells. In the presence of B cells, significantly more infiltrating myeloid cells produced IL-10, TGFβ, and IL-35, and fewer produced TNFα, interferon-γ and IL-6 as compared to controls, up to 2 months post-TBI. B cell treatment significantly increased the proportion of CD206+ infiltrating monocytes/macrophages and reduced the relative proportion of activated microglia starting at 4 days and up to 2 months post-injury. Ablation of peripheral monocytes with clodronate liposomes showed that infiltrating peripheral monocytes/macrophages are required for inducing the regulatory phenotype in exogenous B cells. Reciprocally, B cells specifically reduced the expression of inflammatory cytokines in infiltrating Ly6C+ monocytes/macrophages. These data support the hypothesis that peripheral myeloid cells, particularly infiltrating monocyte/macrophages, are key mediators of the neuroprotective immunomodulatory effects observed after B cell treatment.
Image-based plant wilting estimation
Authors: Yang Changye , Baireddy Sriram , Méline Valérian , Cai Enyu , Caldwell Denise , Iyer-Pascuzzi Anjali S. , Delp Edward J.
Published: May 2023

Background

Environmental stress due to climate or pathogens is a major threat to modern agriculture. Plant genetic resistance to these stresses is one way to develop more resilient crops, but accurately quantifying plant phenotypic responses can be challenging. Here we develop and test a set of metrics to quantify plant wilting, which can occur in response to abiotic stress such as heat or drought, or in response to biotic stress caused by pathogenic microbes. These metrics can be useful in genomic studies to identify genes and genomic regions underlying plant resistance to a given stress.

Results

We use two datasets: one of tomatoes inoculated with Ralstonia solanacearum, a soilborne pathogen that causes bacterial wilt disease, and another of soybeans exposed to water stress. For both tomato and soybean, the metrics predict the visual wilting score provided by human experts. Specific to the tomato dataset, we demonstrate that our metrics can capture the genetic difference of bacterium wilt resistance among resistant and susceptible tomato genotypes. In soybean, we show that our metrics can capture the effect of water stress.

Conclusion

Our proposed RGB image-based wilting metrics can be useful for identifying plant wilting caused by diverse stresses in different plant species.
Chemoradiation for oesophageal cancer: the choice of treatment modality
Authors: Kitti Pauliina M. , Faltinova Maria , Kauppi Juha , Räsänen Jari , Saarto Tiina , Seppälä Tiina , Anttonen Anu M.
Published: May 2023

Background

Locally advanced oesophageal cancer can be treated with definitive chemoradiation (dCRT) or with neoadjuvant chemoradiation followed by surgery (nCRT + S), but treatment modality choice is not always clear. The aim of this study was to investigate the factors associated with the choice of treatment modality in locally advanced oesophageal cancer.

Methods

This was a retrospective cohort study of 149 patients treated with dCRT(n = 85) or nCRT + S (n = 64) for oesophageal cancer in Helsinki University Hospital in 2008–2018. Logistic regression was used to analyse factors associated with choice of treatment modality and to compare dosimetric factors with postoperative complications. Multivariate analyses identified factors associated with survival.

Results

Surgery was performed after chemoradiation as planned on 64/91 patients (70%). 28/64 had pathological complete response (44%). Probability of nCRT + S was higher in stages I-III versus IV (OR 3.62, 95% CI 1.53–8.53; P = .003), ECOG 0–1 versus 2 (OR 6.99, 95% CI 1.81–26.96; P = .005) or in the middle/lower vs upper oesophageal tumours (OR 5.61, 95% CI 1.83–17.16, P = .003). Probability for surgery was lower, if patient had lost > 10% of body weight (OR 0.46, 95% CI 0.21–0.98, P = 0.043). Patients in the nCRT + S group had significantly better median overall survival (mOS) and local control than the dCRT group (60 vs. 10 months, P < .001 and 53 vs. 6 months, P < 0.0001, respectively). 10/85 (12%) patients died within three months after dCRT. In multivariate analysis, nCRT + S was associated with improved mOS (HR 0.28, 95% CI 0.17–0.44, P < .001). Current smokers had worse mOS (HR 2.02, 95% CI 1.04–3.92, P = .037) compared to never-smokers. No significant dosimetric factor associated with postoperative complications was found.

Conclusion

The overall clinical status of the patients and the stage of the cancer guide the choice of treatment modalities, leading to overtreatment. Patients with better prognoses were more likely operated after chemoradiation, although there is no evidence of OS benefit in previous randomized trials. On the other hand, the prognosis was poor for patients with poor general health and advanced cancers, despite the chemoradiation. Thus, there are signs of overtreatment. MDT practice should be recommended to optimise the choice of treatment modalities. Smoking status is an independent factor associated with survival.
New insights in the genetic variant spectrum of SLC34A2 in pulmonary alveolar microlithiasis; a systematic review
Authors: Jönsson Åsa Lina M. , Hilberg Ole , Simonsen Ulf , Christensen Jane Hvarregaard , Bendstrup Elisabeth
Published: May 2023

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in theSLC34A2gene encoding the sodium-dependent phosphate transport protein 2B, NaPi-2b. PAM is characterized by deposition of calcium phosphate crystals in the alveoli. Onset and clinical course vary considerably; some patients remain asymptomatic while others develop severe respiratory failure with a significant symptom burden and compromised survival. It is likely that PAM is under-reported due to lack of recognition, misdiagnosis, and mild clinical presentation. Most patients are genetically uncharacterized as the diagnostic confirmation of PAM has traditionally not included a genetic analysis. Genetic testing may in the future be the preferred tool for diagnostics instead of invasive methods. This systematic review aims to provide an overview of the growing knowledge of PAM genetics. Rare variants inSLC34A2are found in almost all genetically tested patients. So far, 34 allelic variants have been identified in at least 68 patients. A majority of these are present in the homozygous state; however, a few are found in the compound heterozygous form. Most of the allelic variants involve only a single nucleotide. Half of the variants are either nonsense or frameshifts, resulting in premature termination of the protein or decay of the mRNA. There is currently no cure for PAM, and the only effective treatment is lung transplantation. Management is mainly symptomatic, but an improved understanding of the underlying pathophysiology will hopefully result in development of targeted treatment options. More standardized data on PAM patients, including a genetic diagnosis covering larger international populations, would support the design and implementation of clinical studies to the benefit of patients. Further genetic characterization and understanding of how the molecular changes influence disease phenotype will hopefully allow earlier diagnosis and treatment of the disease in the future.
Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling
Authors: Chang Yin-Hsi , Kang Eugene Yu-Chuan , Liu Laura , Jenny Laura A. , Khang Rin , Seo Go Hun , Lee Hane , Chen Kuan-Jen , Wu Wei-Chi , Hsiao Meng-Chang , Wang Nan-Kai
Published: May 2023

Background

Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions.

Results

We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband’s unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before.

Conclusions

In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1. Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.
Looking for answers far away from the soma—the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS
Authors: Ionescu Ariel , Altman Topaz , Perlson Eran
Published: May 2023

Axon degeneration and Neuromuscular Junction (NMJ) disruption are key pathologies in the fatal neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Despite accumulating evidence that axons and NMJs are impacted at a very early stage of the disease, current knowledge about the mechanisms leading to their degeneration remains elusive. Cytoplasmic mislocalization and accumulation of the protein TDP-43 are considered key pathological hallmarks of ALS, as they occur in ~ 97% of ALS patients, both sporadic and familial. Recent studies have identified pathological accumulation of TDP-43 in intramuscular nerves of muscle biopsies collected from pre-diagnosed, early symptomatic ALS patients. These findings suggest a gain of function for TDP-43 in axons, which might facilitate early NMJ disruption. In this review, we dissect the process leading to axonal TDP-43 accumulation and phosphorylation, discuss the known and hypothesized roles TDP-43 plays in healthy axons, and review possible mechanisms that connect TDP-43 pathology to the axon and NMJ degeneration in ALS.
Disulfidptosis: a new form of programmed cell death
Authors: Zheng Tingjin , Liu Qingbo , Xing Feiyue , Zeng Chong , Wang Weidong
Published: May 2023

Disulfidptosis, a new form of cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to the intracellular accumulation of disulfides. This discovery will eventually aid in the development of therapeutic strategies against cancer.
Relationship between the morphology of osteophytes and cartilage lesions in anterior ankle impingement in athletes: a cross‐sectional study
Authors: Yabiku Hiroki , Matsui Tomohiro , Sugimoto Takeshi , Mase Yasuyoshi , Higa Kotaro , Uehara Fuminari , Toma Takashi , Azuma Chinatsu , Tome Yasunori , Nishida Kotaro , Kumai Tsukasa
Published: May 2023

Background

The present study aimed to describe the frequency and severity of tram‐track lesions in anterior ankle impingement in athletes and to evaluate the association between osteophyte morphology and severity of tram‐track lesions, the distinctive cartilage lesions associated with tibial osteophytes in anterior ankle impingement syndrome.

Methods

We evaluated 34 athletes who underwent arthroscopic osteophyte resection for anterior ankle impingement between January 2017 and March 2021.

Results

We found tram‐track lesions in 26 athletes (76.5%). Arthroscopic findings revealed the distribution of the International Cartilage Repair Society grades of tram‐track lesions (grade 0, eight; grade 1, seven; grade 2, ten; grade 3, nine; grade 4, zero). These findings indicate that athletes with anterior ankle impingement syndrome may have more severe cartilage lesions than non‐athletes. There was a positive correlation between the International Cartilage Repair Society grade and osteophyte size (r = 0.393, p = 0.021). We divided athletes into two groups according to the presence or absence of osteophyte protrusion into the joint space. Osteophyte protrusion was present in 14 athletes (41.2%). All athletes in the protrusion‐type group had tram‐track lesions; seven (50%) had International Cartilage Repair Society grade 3. The protrusion‐type group's International Cartilage Repair Society grade was significantly higher than that of the non‐protrusion‐type group (p = 0.008). The osteophyte sizes in the two groups were not significantly different (p = 0.341).

Conclusions

Based on these findings, osteophyte protrusion should be assessed when an indication of arthroscopic treatment for anterior ankle impingement syndrome is considered, particularly in athletes.
Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial
Authors: George Shane , Gibbons Kristen , Williams Tara , Humphreys Susan , Gelbart Ben , Le Marsney Renate , Craig Simon , Tingay David , Chavan Arjun , Schibler Andreas ,   for the Kids THRIVE Investigators, Cronin Joanna , Pearson Kylie , Rasmussen Katie , Acworth Jason , Hickey Leah , Delzoppo Carmel , Perkins Elizabeth , Oberender Felix , Waghorn Jessica , McCahill Courtney , Singhal Nitesh , Harper Gail , Ganu Subodh , Letton Georiga , Erikson Simon , Thomson Hannah , Schlapbach Luregn J. , Burren Juerg , Zimmerman Elisa , Ganeshalingham Anusha , Dalziel Stuart , Sherring Clarie ,   Paediatric Research in Emergency Departments International Collaborative (PREDICT),   the Australia, New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG)
Published: May 2023

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.
Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Authors: Lin Chenhong , Chen Yeda , Zhang Feng , Zhu Peng , Yu Liangliang , Chen Wenbiao
Published: May 2023

Background

Cancer-associated fibroblasts (CAFs) are essential stromal components in the tumor microenvironment of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection induces pathological changes such as liver fibrosis/cirrhosis and HCC. The aim of this research was to explore the novel mediators of CAFs to modulate HBV cirrhosis-HCC progression.

Methods

The single-cell transcriptome data of HCC were divided into subsets, and the significant subset related to fibrotic cells, along with biological function, and clinical information of HCC was revealed by integrated data analyses. The cell communication, cells communicated weight analysis of signaling pathways, and key genes in signaling pathways analysis of significant CAFs subclasses were conducted to discover the novel gene of CAFs. Bioinformatics, vitro and HBV transfection assays were used to verify the novel gene is an important target for promoting the progression HBV cirrhosis-HCC progression.

Results

Fibroblasts derived from HCC single-cell data could be separated into three cell subclasses (CAF0-2), of which CAF2 was associated with the HCC clinical information. Fibroblasts have opposite developmental trajectories to immune B cells and CD8 + T cells. CAF0-2 had strong interaction with B cells and CD8 + T cells, especially CAF2 had the highest interaction frequency and weight with B cells and CD8 + T cells. Moreover, PTN participated in CAF2-related pathways involved in the regulation of cell communication, and the interactions among CAF2 and PTN contributed the most to B cells and CD8 + T cells. Furthermore, the genes of PTN, SDC1, and NCL from PTN signaling were highest expression in CAF2, B cells, and CD8 + T cells, respectively, and the interaction of PTN- SDC1 and PTN- NCL contributed most to the interaction of CAF2- B cells and CAF2-CD8 + T cells. Bioinformatics and vitro experiments confirm PTN was upregulated in HCC and promoted the proliferation of tumor cells, and HBV infection could initiate PTN to perform cirrhosis-HCC progression.

Conclusion

Our findings revealed CAF was associated with hepatocarcinogenesis, and the functional importance of B cells and CD8 + T cells in modulating CAF in HCC. Importantly, PTN maybe a novel mediator of CAF to mediate HBV cirrhosis-HCC progression.