bluuebunny/crossref_metadata_2025 huggingface dataset:
Health care workers’ need for support from managers during the initial phase of the COVID-19 pandemic
Authors: Skogsberg Matilda , Jarl Gustav , Matérne Marie
Published: December 2022

Background

The COVID-19 pandemic placed great pressure on health care workers and increased the risk of these workers developing mental illness. Effective leadership is essential to prevent mental illness from developing. The study aim was to investigate health care workers’ perceptions of the support given by their managers, their need for such support, and their levels of anxiety during the initial phase of the COVID-19 pandemic.

Methods

An electronic study-specific questionnaire was sent to health care workers. A convergent mixed-methods design was used, in which data were analyzed with descriptive statistics, t-tests, and qualitative content analysis.

Results

The majority of the 1074 participants experienced support from a manager who was physically present, caring, and sensitive to their needs, who provided information, and listened to their opinions. Those who did not receive this support experienced more anxiety, and the majority of them expressed a need for this support. A minority of the participants had a manager who scheduled reflection time; few asked for this support, and it was not found to be associated with lower anxiety levels. The qualitative analysis resulted in four themes: 1) A physically present and responsive manager who provides support based on the workers’ needs, 2) The workers understand their manager’s tough work situation and lack of resources, 3) There is a need for clear dissemination of information and participation in organizing the work, and 4) The care of patients is carried out with good cooperation.

Conclusions

The majority of the health care workers received adequate support from their managers. A manager has to be physically present, caring, and supportive to meet the workers’ needs and potentially reduce anxiety levels.
Guest edited collection serological study of SARS-CoV-2 antibodies in japanese cats using protein-A/G-based ELISA
Authors: Imanishi Ichiro , Asahina Ryota , Hayashi Shunji , Uchiyama Jumpei , Hisasue Masaharu , Yamasaki Masahiro , Murata Yoshiteru , Morikawa Shigeru , Mizutani Tetsuya , Sakaguchi Masahiro
Published: December 2022

Background

Little is known about the epidemic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cats in Japan due to insufficiently reliable seroepidemiological analysis methods that are easy to use in cats.

Results

We developed a protein-A/G-based enzyme-linked immunosorbent assay (ELISA) to detect antibodies against SARS-CoV-2 in cats. The assay was standardized using positive rabbit antibodies against SARS-CoV-2. The ELISA results were consistent with those of a conventional anti-feline-immunoglobulin-G (IgG)-based ELISA. To test the protein-A/G-based ELISA, we collected blood samples from 1,969 cats that had been taken to veterinary clinics in Japan from June to July 2020 and determined the presence of anti-SARS-CoV-2 antibodies. Nine cats were found to have SARS-CoV-2 S1-specific IgG, of which 4 had recombinant receptor-binding domain-specific IgG. Of those 9 samples, one showed neutralizing activity. Based on these findings, we estimated that the prevalence of SARS-CoV-2 neutralizing antibodies in cats in Japan was 0.05% (1/1,969 samples). This prevalence was consistent with the prevalence of neutralizing antibodies against SARS-CoV-2 in humans in Japan according to research conducted at that time.

Conclusions

Protein-A/G-based ELISA has the potential to be a standardized method for measuring anti-SARS-CoV-2 antibodies in cats. The infection status of SARS-CoV-2 in cats in Japan might be linked to that in humans.
Identification of key genes and miRNAs related to polycystic ovary syndrome by comprehensive analysis of microarray
Authors: Sun Ziqian , Wang Yang , Wei Tianshu , Liu Li
Published: December 2022

Background

We aimed to explore mechanisms of development and progression of polycystic ovary syndrome (PCOS).

Methods

The microRNA expression microarray GSE37914 and gene expression profiles GSE43264 and GSE98421 were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were screened using Limma package. Then, the DEGs and DEmiRNAs were combined to use for the subsequent analysis, including the functional enrichment analysis, protein–protein interaction (PPI) network and module analysis, drug–gene interaction network analysis, and DEmiRNAs–DEGs interactive network construction.

Results

A total of 26 DEmiRNAs and 80 DEGs were screened. The PPI network contained 68 nodes and 259 interactions. A significant clustering module with 8 nodes and 25 interactions was obtained. Three PCOS-related overlapping pathways were obtained based on PPI-degree top10 and module genes, including prion diseases, Staphylococcus aureus infection, and Chagas disease (American trypanosomiasis). A total of 44 drug–gene interaction pairs were obtained, which included 2 up-regulated genes (LDLR and VCAM1), 4 down-regulated genes (C1QA, C1QB, IL6 and ACAN) and 26 small molecules drugs. A total of 52 nodes and 57 interactions were obtained in the DEmiRNA–DEGs regulatory network, LDLR was regulated by miR-152-3p, miR-1207-5p, miR-378a-5p and miR-150-5p.

Conclusions

Our research has identified several key genes and pathways related to PCOS. These results can improve our understanding of PCOS and provide new basis for drug target research.
Clinical findings and genetic analysis of patients with copy number variants involving 17p13.3 using a single nucleotide polymorphism array: a single-center experience
Authors: Liang Bin , Yu Donghong , Zhao Wantong , Wang Yan , Wu Xiaoqing , Chen Lingji , Lin Na , Huang Hailong , Xu Liangpu
Published: December 2022

Background

17p13.3 microdeletions or microduplications (collectively known as copy number variants or CNVs) have been described in individuals with neurodevelopmental disorders. However, 17p13.3 CNVs were rarely reported in fetuses. This study aims to investigate the clinical significance of 17p13.3 CNVs with varied sizes and gene content in prenatal and postnatal samples.

Methods

Eight cases with 17p13.3 CNVs out of 8806 samples that had been subjected to single nucleotide polymorphism array analysis were retrospectively analyzed, along with karyotyping, clinical features, and follow-up.

Results

Eight cases with 17p13.3 CNVs consisted of five fetuses, one aborted embryo and two probands manifested severe congenital defects. The indications of prenatal testing varied considerably for the five fetuses, including ultrasound abnormalities (n = 3), segmental deletions indicated by non-invasive prenatal testing (n = 1), and intellectual disability in the mother of one fetus (n = 1). Of them, two and six harbored copy number gains and losses involving 17p13.3, respectively. The size of the detected 17p13.3 CNVs ranged from 576 kb to 5.7 Mb. Case 1 was diagnosed with 17p13.3 duplication syndrome, and cases 4, 6, and 7 with Miller–Dieker syndrome (MDS). Microdeletions of the 17p13.3 region in two cases (cases 5 and 8) involving YWHAE and CRK, sparing PAFAH1B1, were classified as pathogenic. Case 2 harbored a 576 kb microduplication, encompassing YWHAE and CRK but not PAFAH1B1, which was of maternal origin and considered a variant of uncertain significance. Case 3 carried one 74.2 Mb mosaic duplication of approximately 3.5 on chromosome 17p13.2q25.3, and two deletions at 17p13.3p13.2 and 17q25.3. The karyotype of case 3 was 46,XY,r(17)(p13q25). For five fetuses, only case 2 continued gestation and showed normal development at the age of 15 months; the others were subjected to termination of pregnancy.

Conclusion

The clinical findings of 17p13.3 microdeletions or microduplications varied among subjects, and 17p13.3 CNVs often differ in size and gene content. Microdeletions or microduplications containing the typical MDS region, as well as the microdeletions involving YWHAE and CRK, could be classified as pathogenic. The clinical significance of small duplications including YWHAE and CRK but not PAFAH1B1 remains uncertain, for which parental testing and clinical heterogeneity should be considered in genetic counseling.
Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
Authors: Liu Ning , Huang Shuo , Guo Fang , Zhai Shafei , Wang Danyang , Li Fang , Liu Changkui
Published: December 2022

Background

Icariin (ICA), a main active ingredient of Herba Epimedium, could promote bone formation, inhibit bone resorption and alleviate inflammatory responses. The aim of this study was to investigate the effect of ICA on the inhibition of bacteria associated with peri-implantitis, and fabricate a calcium phosphate cement (CPC) with ICA-loaded gelatin microspheres (GMs) as a local drug delivery system efficiently promoting bone formation and alleviating inflammation.

Results

In this study, ICA exhibited antibacterial activity against P. gingivalis with a MIC value of 1 × 10–4 mol/L. When the concentration of ICA was 0.5 mM, the encapsulation efficiency of GMs reached the maximum value of 76.26 ± 3.97%. GMs with ICA revealed a controlled release profile, 0.5 mM ICA exhibited a higher ICA release profile than the other groups during a 21 d monitoring span. The results of SEM and XRD demonstrated successful fabrication of a calcium phosphate cement with ICA-loaded GMs. ICA released from CPC/GMs (ICA) was slower than ICA released from GMs within 10 days. CPC/GMs (ICA) exhibited antibacterial activity against P. gingivalis, but the antibacterial rate of CPC/GMs (ICA) was only 17.15 ± 6.06%. In addition, CPC/GMs (ICA) promoted the proliferation of BMSCs and significantly stimulated the differentiation and maturation of BMSCs. In vivo, H&E and Masson staining experiments demonstrated that CPC/GMs (ICA) exhibited better capacity for bone regeneration than CPC/GMs and CPC, and the expression of TNF-α and IL-1β in the tissue around CPC/GMs (ICA) was significantly lower than CPC/GMs and CPC in IHC staining (P < 0.05).

Conclusion

In this study, ICA exhibited limited antibacterial activity against bacteria associated with peri-implantitis. A composite material of calcium phosphate cement with ICA-loaded gelatin microspheres was developed, which not only promoting osteoinductivity and bone formation, but also alleviating inflammation, demonstrating its potential as a promising bone substitute material for treatment of peri-implantitis.
Extracellular vesicle microRNAs contribute to Notch signaling pathway in T-cell acute lymphoblastic leukemia
Authors: Colangelo Tommaso , Panelli Patrizio , Mazzarelli Francesco , Tamiro Francesco , Melocchi Valentina , De Santis Elisabetta , Cuttano Roberto , Palumbo Orazio , Rossi Giovanni , Bianchi Fabrizio , Giambra Vincenzo
Published: December 2022

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy characterized by genotypically-defined and phenotypically divergent cell populations, governed by adaptive landscapes. Clonal expansions are associated to genetic and epigenetic events, and modulation of external stimuli that affect the hierarchical structure of subclones and support the dynamics of leukemic subsets. Recently, small extracellular vesicles (sEV) such as exosomes were also shown to play a role in leukemia. Here, by coupling miRNome, bulk and single cell transcriptome profiling, we found that T-ALL-secreted sEV contain NOTCH1-dependent microRNAs (EV-miRs), which control oncogenic pathways acting as autocrine stimuli and ultimately promoting the expansion/survival of highly proliferative cell subsets of human T-cell leukemias. Of interest, we found that NOTCH1-dependent EV-miRs mostly comprised members of miR-17-92a cluster and paralogues, which rescued in vitro the proliferation of T-ALL cells blocked by γ-secretase inhibitors (GSI) an regulated a network of genes characterizing patients with relapsed/refractory early T-cell progenitor (ETP) ALLs. All these findings suggest that NOTCH1 dependent EV-miRs may sustain the growth/survival of immunophenotypically defined cell populations, altering the cell heterogeneity and the dynamics of T-cell leukemias in response to conventional therapies.
The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus
Authors: Alibolandi Zahra , Ostadian Amirreza , Sayyah Saeed , Haddad Kashani Hamed , Ehteram Hassan , Banafshe Hamid Reza , Hajijafari Mohammad , Sepehrnejad Mahdi , Riahi Kashani Narjes , Azadchehr Mohammd-Javad , Nikzad Hossein , Seyed Hosseini Elahe
Published: December 2022

Objectives

This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity.

Methods

IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission.

Results

The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital.

Conclusion

Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.
Biomimetic cell-derived nanocarriers in cancer research
Authors: Soprano Enrica , Polo Ester , Pelaz Beatriz , del Pino Pablo
Published: December 2022

Nanoparticles have now long demonstrated capabilities that make them attractive to use in biology and medicine. Some of them, such as lipid nanoparticles (SARS-CoV-2 vaccines) or metallic nanoparticles (contrast agents) are already approved for their use in the clinic. However, considering the constantly growing body of different formulations and the huge research around nanomaterials the number of candidates reaching clinical trials or being commercialized is minimal. The reasons behind being related to the “synthetic” and “foreign” character of their surface. Typically, nanomaterials aiming to develop a function or deliver a cargo locally, fail by showing strong off-target accumulation and generation of adverse responses, which is connected to their strong recognition by immune phagocytes primarily. Therefore, rendering in negligible numbers of nanoparticles developing their intended function. While a wide range of coatings has been applied to avoid certain interactions with the surrounding milieu, the issues remained. Taking advantage of the natural cell membranes, in an approach that resembles a cell transfer, the use of cell-derived surfaces has risen as an alternative to artificial coatings or encapsulation methods. Biomimetic technologies are based on the use of isolated natural components to provide autologous properties to the nanoparticle or cargo being encapsulated, thus, improving their therapeutic behavior. The main goal is to replicate the (bio)-physical properties and functionalities of the source cell and tissue, not only providing a stealthy character to the core but also taking advantage of homotypic properties, that could prove relevant for targeted strategies. Such biomimetic formulations have the potential to overcome the main issues of approaches to provide specific features and identities synthetically. In this review, we provide insight into the challenges of nano-biointerfaces for drug delivery; and the main applications of biomimetic materials derived from specific cell types, focusing on the unique strengths of the fabrication of novel nanotherapeutics in cancer therapy.

Graphical Abstract
Downregulation of SMIM3 inhibits growth of leukemia via PI3K-AKT signaling pathway and correlates with prognosis of adult acute myeloid leukemia with normal karyotype
Authors: Liu Yu , Chen Yufei , Liu Yajun , Li Mengya , Zhang Yu , Shi Luyao , Yang Lu , Li Tao , Li Yafei , Jiang Zhongxing , Liu Yanfang , Wang Chong , Wang Shujuan
Published: December 2022

Background

Acute myeloid leukemia (AML) patients with normal karyotype (NK-AML) have significant variabilities in outcomes. The European Leukemia Net stratification system and some prognostic models have been used to evaluate risk stratification. However, these common standards still have some limitations. The biological functions and mechanisms of Small Integral Membrane Protein 3 (SMIM3) have seldomly been investigated. To this date, the prognostic value of SMIM3 in AML has not been reported. This study aimed to explore the clinical significance, biological effects and molecular mechanisms of SMIM3 in AML.

Methods

RT-qPCR was applied to detect the expression level of SMIM3 in bone marrow specimens from 236 newly diagnosed adult AML patients and 23 healthy volunteers. AML cell lines, Kasumi-1 and THP-1, were used for lentiviral transfection. CCK8 and colony formation assays were used to detect cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to explore relevant signaling pathways. The biological functions of SMIM3 in vivo were validated by xenograft tumor mouse model. Survival rate was evaluated by Log-Rank test and Kaplan–Meier. Cox regression model was used to analyze multivariate analysis. The correlations between SMIM3 and drug resistance were also explored.

Results

Through multiple datasets and our clinical group, SMIM3 was shown to be significantly upregulated in adult AML compared to healthy subjects. SMIM3 overexpression conferred a worse prognosis and was identified as an independent prognostic factor in 95 adult NK-AML patients. Knockdown of SMIM3 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. The reduced SMIM3 expression significantly suppressed tumor growth in the xenograft mouse model. Western blot analysis showed downregulation of p-PI3K and p-AKT in SMIM3-knockdown AML cell lines. SMIM3 may also be associated with some PI3K-AKT and first-line targeted drugs.

Conclusions

SMIM3 was highly expressed in adult AML, and such high-level expression of SMIM3 was associated with a poor prognosis in adult AML. Knockdown of SMIM3 inhibited the proliferation of AML through regulation of the PI3K-AKT signaling pathway. SMIM3 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
The YTHDF1–TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray
Authors: Ouyang Handong , Zhang Jianxing , Chi Dongmei , Zhang Kun , Huang Yongtian , Huang Jingxiu , Huang Wan , Bai Xiaohui
Published: December 2022

Long-term use of opioids such as morphine has negative side effects, such as morphine analgesic tolerance and morphine-induced hyperalgesia (MIH). These side effects limit the clinical use and analgesic efficacy of morphine. Elucidation of the mechanisms and identification of feasible and effective methods or treatment targets to solve this clinical phenomenon are important. Here, we discovered that YTHDF1 and TNF receptor-associated factor 6 (TRAF6) are crucial for morphine analgesic tolerance and MIH. The m6A reader YTHDF1 positively regulated the translation of TRAF6 mRNA, and chronic morphine treatments enhanced the m6A modification of TRAF6 mRNA. TRAF6 protein expression was drastically reduced by YTHDF1 knockdown, although TRAF6 mRNA levels were unaffected. By reducing inflammatory markers such as IL-1β, IL-6, TNF-α and NF-κB, targeted reduction of YTHDF1 or suppression of TRAF6 activity in ventrolateral periaqueductal gray (vlPAG) slows the development of morphine analgesic tolerance and MIH. Our findings provide new insights into the mechanism of morphine analgesic tolerance and MIH indicating that YTHDF1 regulates inflammatory factors such as IL-1β, IL-6, TNF-α and NF-κB by enhancing TRAF6 protein expression.
Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma
Authors: Potkrajcic Vlatko , Kolbenschlag Jonas , Sachsenmaier Saskia , Daigeler Adrien , Ladurner Ruth , Golf Alexander , Gani Cihan , Zips Daniel , Paulsen Frank , Eckert Franziska
Published: December 2022

Background

Standard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (± chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and postoperative complications in patients treated with multimodal treatment.

Methods

Oncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in 74 patients with localized high-risk soft tissue sarcoma of extremities and trunk undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant vs. adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications.

Results

Oncologic outcomes were dependent on number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. Slightly higher MWC-rates were observed in patients treated with neoadjuvant therapy, compared to adjuvant radiotherapy, although only with a trend to statistical significance (31.8% vs. 13.3%, p = 0.059). However, except for wound infections, no significant difference for other subclasses of postoperative complications was observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications.

Conclusion

Rates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Tumor localization, patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence DMFS. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.
Effect of mechanical ventilation during cardiopulmonary bypass on end-expiratory lung volume in the perioperative period of cardiac surgery: an observational study
Authors: Trancart Léa , Rey Nathalie , Scherrer Vincent , Wurtz Véronique , Bauer Fabrice , Aludaat Chadi , Demailly Zoe , Selim Jean , Compère Vincent , Clavier Thomas , Besnier Emmanuel
Published: December 2022

Background

Many studies explored the impact of ventilation during cardiopulmonary bypass (CPB) period with conflicting results. Functional residual capacity or End Expiratory Lung Volume (EELV) may be disturbed after cardiac surgery but the specific effects of CPB have not been studied. Our objective was to compare the effect of two ventilation strategies during CPB on EELV.

Methods

Observational single center study in a tertiary teaching hospital. Adult patients undergoing on-pump cardiac surgery by sternotomy were included. Maintenance of ventilation during CPB was left to the discretion of the medical team, with division between "ventilated" and "non-ventilated" groups afterwards. Iterative intra and postoperative measurements of EELV were carried out by nitrogen washin-washout technique. Main endpoint was EELV at the end of surgery. Secondary endpoints were EELV one hour after ICU admission, PaO2/FiO2 ratio, driving pressure, duration of mechanical ventilation and post-operative pulmonary complications.

Results

Forty consecutive patients were included, 20 in each group. EELV was not significantly different between the ventilated versus non-ventilated groups at the end of surgery (1796 ± 586 mL vs. 1844 ± 524 mL, p = 1) and one hour after ICU admission (2095 ± 562 vs. 2045 ± 476 mL, p = 1). No significant difference between the two groups was observed on PaO2/FiO2 ratio (end of surgery: 339 ± 149 vs. 304 ± 131, p = 0.8; one hour after ICU: 324 ± 115 vs. 329 ± 124, p = 1), driving pressure (end of surgery: 7 ± 1 vs. 8 ± 1 cmH2O, p = 0.3; one hour after ICU: 9 ± 3 vs. 9 ± 3 cmH2O), duration of mechanical ventilation (5.5 ± 4.8 vs 8.2 ± 10.0 h, p = 0.5), need postoperative respiratory support (2 vs. 1, p = 1), occurrence of pneumopathy (2 vs. 0, p = 0.5) and radiographic atelectasis (7 vs. 8, p = 1).

Conclusion

No significant difference was observed in EELV after cardiac surgery between not ventilated and ventilated patients during CPB.
Growth hormone treatment improves final height in children with X-linked hypophosphatemia
Authors: André Julia , Zhukouskaya Volha V. , Lambert Anne-Sophie , Salles Jean-Pierre , Mignot Brigitte , Bardet Claire , Chaussain Catherine , Rothenbuhler Anya , Linglart Agnès
Published: December 2022

Background/aim

Despite optimal conventional treatment (oral phosphate supplements and active vitamin D analogs), about 40–50% of children with well-controlled X-linked hypophosphatemia (XLH) show linear growth failure, making them less likely to achieve an acceptable final height. Here, we studied the hypothesis that rhGH treatment improves final height in children with XLH and growth failure.

Methods

Two cohorts of children with XLH were included in this retrospective longitudinal analysis: (1) a cohort treated with rhGH for short stature (n = 34) and (2) a cohort not treated with rhGH (n = 29). The mean duration of rhGH treatment was 4.4 ± 2.9 years. We collected the auxological parameters at various time points during follow-up until final height.

Results

In rhGH-treated children, 2 years of rhGH therapy was associated with a significant increase in height from − 2.4 ± 0.9 to − 1.5 ± 0.7 SDS (p < 0.001). Their mean height at rhGH discontinuation was − 1.2 ± 0.9 SDS and at final height was − 1.3 ± 0.9 SDS corresponding to 165.5 ± 6.4 cm in boys and 155.5 ± 6.3 cm in girls. Notably, the two groups had similar final heights; i.e., the final height in children not treated with rhGH being − 1.2 ± 1.1 SDS (165.4 ± 6.8 cm in boys and 153.7 ± 7.8 cm in girls), p = 0.7.

Conclusion

Treatment with rhGH permits to improve final height in children with XLH and growth failure, despite optimal conventional treatment. We propose therefore that rhGH therapy could be considered as an option for short stature in the context of XLH.
Predictors of chronic loneliness during adolescence: a population-based cohort study
Authors: Hosozawa Mariko , Cable Noriko , Yamasaki Syudo , Ando Shuntaro , Endo Kaori , Usami Satoshi , Nakanishi Miharu , Niimura Junko , Nakajima Naomi , Baba Kaori , Oikawa Nao , Stanyon Daniel , Suzuki Kazuhiro , Miyashita Mitsuhiro , Iso Hiroyasu , Hiraiwa-Hasegawa Mariko , Kasai Kiyoto , Nishida Atsushi
Published: December 2022

Background

Adolescent loneliness is a growing public health issue owing to its adverse health impact. Although adolescent loneliness is common, its trajectories can show distinct patterns over time. However, there is limited knowledge regarding their determinants, particularly for chronic loneliness. We aimed to determine the predictors of loneliness trajectories across early-to-mid adolescence and examine their association with later suicidality.

Methods

Data were collected from 3165 participants from the population-based Tokyo Teen Cohort. Participants reported their loneliness at 10, 12, 14, and 16 years. Loneliness trajectories were identified using latent class growth analysis. We examined the predictive role of bullying victimization and parental psychological distress at age 10 via a multinomial logistic regression. Sociodemographic and child-related factors (i.e., chronic health conditions and cognitive delay) were included as covariates. The association between the trajectories, self-harm, and suicidal ideation by age 16 was investigated using Poisson regression.

Results

Four trajectories were identified: “consistently low” (2448, 77.3%), “moderate–decreasing” (185, 5.8%), “moderate–increasing” (508, 16.1%), and “consistently high” (24, 0.8%). Taking “consistently low” as a reference, experiences of bullying victimization predicted all the remaining trajectories [adjusted relative risk ratio 1.64, 95% confidence interval (CI) 1.18–2.28 for “moderate–decreasing,” 1.88, 1.52–2.33 for “moderate–increasing,” and 4.57, 1.97–10.59 for “consistently high”]. Parental psychological distress predicted the “moderate–increasing” (1.84, 1.25–2.71) and “consistently high” (5.07, 1.78–14.42) trajectories. The “consistently high” trajectory showed the greatest risk for self-harm and suicidal ideation (adjusted relative risk ratio 6.01, 95% CI 4.40–8.22; 2.48, 1.82–3.37, respectively); however, the “moderate–increasing” and “moderate–decreasing” trajectories were also at increased risk (moderate–increasing: 2.71, 2.23–3.30 for self-harm, 1.93, 1.69–2.19 for suicidal ideation; moderate–decreasing: 2.49, 1.91–3.26 for self-harm, 1.59, 1.33–1.91 for suicidal ideation).

Conclusions

Bullying victimization and parental psychological distress at age 10 were independent determinants of increased and chronic loneliness trajectories across early-to-mid adolescence. Compared with “consistently low,” all other loneliness trajectories were associated with an increased risk of adolescent suicidality. Interventions targeting adolescent loneliness should include approaches to mitigate bullying and parental psychological distress. These strategies may help prevent adolescent suicidality.
Chronic skin ultraviolet irradiation induces transcriptomic changes associated with microglial dysfunction in the hippocampus
Authors: Yoon Kyeong-No , Kim Yujin , Cui Yidan , Ji Jungeun , Park Gunhyuk , Chung Jin Ho , Lee Yong-Seok , An Joon-Yong , Lee Dong Hun
Published: December 2022

Recent evidence indicates that ultraviolet (UV) exposure of the skin can affect brain functions such as learning and memory, addictive behavior, and hippocampal neurogenesis. These changes are closely associated with hippocampal function, which plays a pivotal role in learning and memory formation. However, the molecular mechanisms underlying these UV-induced skin-brain interactions remain unclear. To elucidate the molecular signature associated with UV-induced neurobehavioral changes, we analyzed the hippocampal transcriptome in a well-established mouse skin aging model, which showed thickened skin and impaired hippocampal memory. Transcriptome analysis revealed that significantly downregulated genes in UV-irradiated mice are enriched in neuroimmune-related signaling pathways. Furthermore, cell-type analysis showed that DEGs are also enriched in microglia. Consistently, immunofluorescence imaging showed an increased number of Iba1-positive microglia in the hippocampi of UV-irradiated mice. Collectively, our findings highlight that chronic UV irradiation of the skin causes significant changes in the neuroimmune system in the hippocampus, accompanied by microglial dysfunction and cognitive impairment.
T-cell repertoire diversity: friend or foe for protective antitumor response?
Authors: Porciello Nicla , Franzese Ornella , D’Ambrosio Lorenzo , Palermo Belinda , Nisticò Paola
Published: December 2022

Profiling the T-Cell Receptor (TCR) repertoire is establishing as a potent approach to investigate autologous and treatment-induced antitumor immune response. Technical and computational breakthroughs, including high throughput next-generation sequencing (NGS) approaches and spatial transcriptomics, are providing unprecedented insight into the mechanisms underlying antitumor immunity. A precise spatiotemporal variation of T-cell repertoire, which dynamically mirrors the functional state of the evolving host-cancer interaction, allows the tracking of the T-cell populations at play, and may identify the key cells responsible for tumor eradication, the evaluation of minimal residual disease and the identification of biomarkers of response to immunotherapy. In this review we will discuss the relationship between global metrics characterizing the TCR repertoire such as T-cell clonality and diversity and the resultant functional responses. In particular, we will explore how specific TCR repertoires in cancer patients can be predictive of prognosis or response to therapy and in particular how a given TCR re-arrangement, following immunotherapy, can predict a specific clinical outcome. Finally, we will examine current improvements in terms of T-cell sequencing, discussing advantages and challenges of current methodologies.
Perspective: the top 11 priorities to improve trauma outcomes, from system to patient level
Authors: Reade Michael C.
Published: December 2022

Background

The Haemorrhage, Airway, Breathing, Circulation, Disability, Exposure/Environmental control approach to individual patient management in trauma is well established and embedded in numerous training courses worldwide. Further improvements in trauma outcomes are likely to result from a combination of system-level interventions in prevention and quality improvement, and from a sophisticated approach to clinical innovation.

Top eleven trauma priorities

Based on a narrative review of remaining preventable mortality and morbidity in trauma, the top eleven priorities for those working throughout the spectrum of trauma care, from policy-makers to clinicians, should be: (1) investment in effective trauma prevention (likely to be the most cost-effective intervention); (2) prioritisation of resources, quality improvement and innovation in prehospital care (where the most preventable mortality remains); (3) building a high-performance trauma team; (4) applying evidence-based clinical interventions that stop bleeding, open & protect the airway, and optimise breathing most effectively; (5) maintaining enough circulating blood volume and ensuring adequate cardiac function; (6) recognising the role of the intensive care unit in modern damage control surgery; (7) prioritising good intensive care unit intercurrent care, especially prophylaxis for thromboembolic disease; (8) conducting a thorough tertiary survey, noting that on average the intensive care unit is where approximately 15% of injuries are detected; (9) facilitating early extubation; (10) investing in formal quantitative and qualitative quality assurance and improvement; and (11) improving clinical trial design.

Conclusion

Dramatic reductions in population trauma mortality and injury case fatality rate over recent decades have demonstrated the value of a comprehensive approach to trauma quality and process improvement. Continued attention to these principles, targeting areas with highest remaining preventable mortality while also prioritising functional outcomes, should remain the focus of both clinician and policy-makers.
The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial
Authors: Ahlin Rebecca , Nybacka Sanna , Josefsson Andreas , Stranne Johan , Steineck Gunnar , Hedelin Maria
Published: December 2022

Background

A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERβ) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERβ gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERβ genotype on prostate tumor proliferation in patients with prostate cancer.

Method

The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERβ will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood.

Discussion

The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer.

Trial registration.

ClinicalTrials.gov NCT02759380. Registered on 3 May 2016.
Characterizing chromatin interactions of regulatory elements and nucleosome positions, using Hi-C, Micro-C, and promoter capture Micro-C
Authors: Lee Beoung Hun , Wu Zexun , Rhie Suhn K.
Published: December 2022

Background

Regulatory elements such as promoters, enhancers, and insulators interact each other to mediate molecular processes. To capture chromatin interactions of regulatory elements, 3C-derived methods such as Hi-C and Micro-C are developed. Here, we generated and analyzed Hi-C, Micro-C, and promoter capture Micro-C datasets with different sequencing depths to study chromatin interactions of regulatory elements and nucleosome positions in human prostate cancer cells.

Results

Compared to Hi-C, Micro-C identifies more high-resolution loops, including ones around structural variants. By evaluating the effect of sequencing depth, we revealed that more than 2 billion reads of Micro-C are needed to detect chromatin interactions at 1 kb resolution. Moreover, we found that deep-sequencing identifies additional long-range loops that are longer than 1 Mb in distance. Furthermore, we found that more than 50% of the loops are involved in insulators while less than 10% of the loops are promoter–enhancer loops. To comprehensively capture chromatin interactions that promoters are involved in, we performed promoter capture Micro-C. Promoter capture Micro-C identifies loops near promoters with a lower amount of sequencing reads. Sequencing of 160 million reads of promoter capture Micro-C resulted in reaching a plateau of identifying loops. However, there was still a subset of promoters that are not involved in loops even after deep-sequencing. By integrating Micro-C with NOMe-seq and ChIP-seq, we found that active promoters involved in loops have a more accessible region with lower levels of DNA methylation and more highly phased nucleosomes, compared to active promoters that are not involved in loops.

Conclusion

We determined the required sequencing depth for Micro-C and promoter capture Micro-C to generate high-resolution chromatin interaction maps and loops. We also investigated the effect of sequencing coverage of Hi-C, Micro-C, and promoter capture Micro-C on detecting chromatin loops. Our analyses suggest the presence of distinct regulatory element groups, which are differently involved in nucleosome positions and chromatin interactions. This study does not only provide valuable insights on understanding chromatin interactions of regulatory elements, but also present guidelines for designing research projects on chromatin interactions among regulatory elements.
Comparative study of stunting measurement in children using WHO procedure and Growth Length Mat in Ghana
Authors: Bukari Nafisatu , Danaa Alhassan , Mubarak Abdulai , Forfoe Wilfred W. , Gariba Ayishetu , Ali Zakari
Published: December 2022

Objective

Height data is not useful immediately without further processing. The Growth Length Mat (Stunting Mat) was designed to stunting directly. However, the Mat has not been validated for use in Ghana. This study compared stunting measured with the Mat and stunting measured following the WHO recommended procedure. We sampled 163 children aged 6–24 months in the Bono region of Ghana. We also explored the acceptability and interpretability of the two procedures among mothers and healthcare givers.

Results

The prevalence of stunting was 3.7% and 11.7% using the Mat and WHO procedures respectively. The Growth Length Mat had very low sensitivity (21.0%) but high specificity (98.6%) of detecting stunting in children. However, in younger aged children, the Mat was more accurate in detecting stunting. Both healthcare workers and caregivers found it easy to interpret the stunting status of children using the Mat. We conclude that the Growth Length Mat was less sensitive at detecting child stunting compared to the current gold standard of measuring stunting in younger children. There are possibilities to improve the accuracy and utility of the Mat for measuring stunting in low-resource settings by re-designing the mat to be more age appropriate.
Hypersensitivity reactions to folinic acid: mechanisms involved based on two case reports and a literature review
Authors: Apraxine Matveï , Van den Eynde Marc , De Cuyper Astrid , Pirson Françoise
Published: December 2022

Background

Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA.

Case presentation

Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly.

Conclusions

These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner’s attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.
Automatic segmentation of prostate zonal anatomy on MRI: a systematic review of the literature
Authors: Wu Carine , Montagne Sarah , Hamzaoui Dimitri , Ayache Nicholas , Delingette Hervé , Renard-Penna Raphaële
Published: December 2022

Objectives

Accurate zonal segmentation of prostate boundaries on MRI is a critical prerequisite for automated prostate cancer detection based on PI-RADS. Many articles have been published describing deep learning methods offering great promise for fast and accurate segmentation of prostate zonal anatomy. The objective of this review was to provide a detailed analysis and comparison of applicability and efficiency of the published methods for automatic segmentation of prostate zonal anatomy by systematically reviewing the current literature.

Methods

A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was conducted until June 30, 2021, using PubMed, ScienceDirect, Web of Science and EMBase databases. Risk of bias and applicability based on Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria adjusted with Checklist for Artificial Intelligence in Medical Imaging (CLAIM) were assessed.

Results

A total of 458 articles were identified, and 33 were included and reviewed. Only 2 articles had a low risk of bias for all four QUADAS-2 domains. In the remaining, insufficient details about database constitution and segmentation protocol provided sources of bias (inclusion criteria, MRI acquisition, ground truth). Eighteen different types of terminology for prostate zone segmentation were found, while 4 anatomic zones are described on MRI. Only 2 authors used a blinded reading, and 4 assessed inter-observer variability.

Conclusions

Our review identified numerous methodological flaws and underlined biases precluding us from performing quantitative analysis for this review. This implies low robustness and low applicability in clinical practice of the evaluated methods. Actually, there is not yet consensus on quality criteria for database constitution and zonal segmentation methodology.