bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy
Authors: Farooqui Naba , Subbiah Arunkumar , Chaturvedi Pradeep , Sati Hem , Singh Geetika , Bhowmik Dipankar , Agarwal Sanjay K. , Bagchi Soumita
Published: January 2023

Background

Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN).

Methods

In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency.

Results

Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 – 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50–6.34, p = 0.368).

Conclusion

There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.
A case report of autoimmune GFAP astrocytopathy presenting with abnormal heart rate variability and blood pressure variability
Authors: Wen Pu-yuan , Wang Guang-qiang , Dou Lian-wei , Chen Qi , Chen Xian-wen , Gong Li
Published: January 2023

Background

Autonomic dysfunctions including bladder dysfunction, gastrointestinal dysfunction and orthostasis are common symptoms of autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A); however, cardiac autonomic dysfunction and abnormal circadian rhythm of blood pressure, which can lead to poor prognosis and even sudden cardiac death, has never been reported in A-GFAP-A patient.

Case presentation

A 68-year-old male Chinese patient presented to our hospital with headache, fever, progressive disturbance of consciousness, dysuria, and limb weakness. Abnormal heart rate variability and non-dipper circadian rhythm of blood pressure gradually developed during hospitalization, which is rare in A-GFAP-A. He had positive GFAP IgG in cerebrospinal fluid (CSF). Enhanced brian MRI showed uneven enhancement and T2 hyperintense lesions of medulla oblongata; Cervical spine MRI showed T2 hyperintense lesions in medulla oblongata and upper margin of the T2 vertebral body. A contrast-enhanced thoracic spine MRI showed uneven enhancement and T2 hyperintense lesions of T1 to T6 vertebral segments. After treatment with intravenous immunoglobulin and corticosteroids, the patient’s symptoms, including autonomic dysfunction, alleviated dramatically. Finally, his heart rate variability and blood pressure variability became normal.

Conclusions

Our case broadens the spectrum of expected symptoms in A-GFAP- A syndromes as it presented with heart rate variability and blood pressure variability.
A comparative study of transscleral sutured intraocular lens fixation and sutureless flanged intraocular lens fixation
Authors: Cui Ying , Li Qiyan , Shi Xiangyu , Zhou Dan
Published: January 2023

Background

To compare the intraocular lens (IOL) tilt and decentration and visual outcomes of transscleral sutured IOL fixation and sutureless flanged IOL fixation. To investigate the influence of IOL tilt and decentration on internal higher-order aberrations (HOAs) in these two techniques.

Methods

Patients who received transscleral sutured or sutureless flanged IOL fixation procedures were included in this prospective, non-randomized, comparative study. Corrected distance visual acuity (CDVA) was measured at baseline and at every postoperative visit for 12 months. IOL tilt and decentration were measured using a second-generation anterior segment optical coherence tomography (Casia2) and internal HOAs were measured using iTrace Visual Function Analyzer at 3 months postoperatively.

Results

The study included 27 eyes from the transscleral sutured IOL fixation group and 26 eyes from the sutureless flanged IOL fixation group. There was no significant difference in CDVA between the two groups at all time points. The two groups did not differ in refractive difference from the predicted value, corneal endothelial cell loss, IOL tilt, IOL decentration, internal astigmatism or internal HOAs. Vertical IOL decentration significantly correlated with total internal optical aberration (r = 0.288, P = 0.036), total internal HOA (r = 0.440, P = 0.001), internal coma (r = 0.348, P = 0.001), vertical internal coma (r = 0.388, P = 0.004), average height of modulation transfer function (r = − 0.364, P = 0.007) and Strehl ratio (r = − 0.297, P = 0.031). Horizontal IOL decentration significantly correlated with horizontal internal coma (r = 0.312, P = 0.023).

Conclusions

Transscleral sutured IOL fixation and sutureless flanged IOL fixation had similar IOL positions and visual outcomes. IOL decentrations correlated with internal HOAs and thus should be avoided.
Do symptoms moderate the association between participation and executive functions outcomes among people with schizophrenia?
Authors: Kaizerman-Dinerman Alona , Roe David , Demeter Naor , Josman Naomi
Published: January 2023

Background

Literature explains participation limitations among people with schizophrenia through the context of metacognitive limitations, specifically in symptoms and in executive functions (EF). Research has shown mixed results regarding associations between symptoms and participation, reporting association with negative symptoms, positive symptoms, or only metacognitive limitations. The aim of this study was to deepen understanding of the symptoms’ impact on the association between participation and executive function among people with schizophrenia.

Methods

Forty-three participants with schizophrenia received 8 group sessions of focused metacognitive intervention (MCG) aimed at promoting participation by focusing on EF components (e.g., analyzing individual cognitive strategy use). Three measures were administered: the Positive and Negative Syndrome Scale (PANSS) to evaluate symptoms, the Weekly Calendar Planning Assessment (WCPA) to assess EF, and the Activity Card Sort (ACS) to measure participation at the baseline and 12 weeks following completion of the intervention. Scores were compared to a matched control group of 41 people with schizophrenia who instead received treatment as usual. The role of PANSS as moderator was examined using multiple hierarchical regressions, entering interactions between the PANSS scores and WCPA change scores in the final regression step.

Results

Relationships were not significant for participants with high PANSS scores. A positive relationship existed between change in WCPA and change in ACS for participants with low PANSS scores.

Conclusions

These results demonstrate that low PANSS scores moderate the association between EF and participation and highlight the importance of symptoms as a predictor of participation following the MCG intervention.

Trial registration

The trial was retrospectively registered at clinical.trial.gov. ClinicalTrials.gov Identifier: NCT05556941. Clinicaltrial.gov registration date: 27/09/2022.
Association between public health emergencies and sexual and reproductive health, gender-based violence, and early marriage among adolescent girls: a rapid review
Authors: Shukla Shruti , Ezebuihe Jessy Amarachi , Steinert Janina Isabel
Published: January 2023

Background

As COVID-19 continues to impact lives and livelihoods around the world, women and girls are disproportionately affected. Crisis situations and related response measures, such as lockdowns, school closures, and travel restrictions, often exacerbate the adversities and human rights violations faced by adolescent girls. We conducted a rapid review to synthesise evidence on the impact of public health emergencies (PHEs) related to gender-based inequalities among adolescent girls.

Methods

We systematically searched five major databases. Records were imported into the online screening tool Rayyan, and 10% of the records were triple screened for eligibility. We included qualitative, mixed-methods, and quantitative studies that assessed the relationship between PHEs and any of the following outcomes: (1) gender-based violence, (2) early/forced marriage, and (3) sexual and reproductive health. Due to the heterogeneity of included study designs, no meta-analysis was performed, and studies were summarised narratively.

Findings

Out the initial 6004 articles, 11 studies met our eligibility criteria. Five of these assessed the impact of natural disasters and six were focused on consequences of the COVID-19 pandemic. Seven studies focused on the impact of PHEs on gender-based violence, three focused on sexual and reproductive health, and only one study looked at early marriage. The main impacts highlighted by the studies included (1) increases in physical, psychological, and sexual abuse, (2) increase in the occurrence of teenage pregnancy, (3) poor menstruation hygiene management, and (4) occurrence of early marriages. Mechanisms underlying these impacts were PHE-specific response strategies like home confinement, closure of schools, the worsening of families’ financial situation such as the inability to pay for school fees or day-to-day living costs, and the disempowerment of and increased workloads for adolescent girls.

Conclusion

Although evidence on the impact of COVID-19 on gender-based violence, sexual and reproductive health, and especially forced or early marriage of adolescent girls is limited, results from studies on other PHEs indicate that during crises, these detrimental outcomes are exacerbated. Findings from our review have important implications for policies and programs providing life skills training, financial literacy training, credit support, and safe spaces for adolescent girls.
A retrospective study regarding the influence of COVID-19 disease on asthma
Authors: Muntean Ioana Adriana , Leru Polliana Mihaela , Pintea Irena , Bocsan Ioana Corina , Dobrican Carmen Teodora , Deleanu Diana
Published: January 2023

Background

During the Covid-19 pandemic patients suffering from asthma raised many concerns regarding the outcome ofthe impact of COVID-19 disease on their preexisting condition. The 2021 GINA report indicates that people with asthma do not appear to be at increased risk of a severe form of COVID-19.

Method

This study is a retrospective study of patients (n = 163) median age = 27.8 years, M:F = 1:1.26, with asthma evaluated using ACT (asthma control test) and VAS (visual analog scale) before and after COVID-19 disease. An ACT score over 20 points placed patients in the controlled asthma group.

Results

The overall evaluation for COVID-19 in our asthma patients revealed that 22.7% of the studied group had the COVID-19 disease (21.5% in the controlled asthma group and 24.5% in uncontrolled asthma group). Asthma disease history was longer in the uncontroled asthma group (128 ± 96.8 months vs. 296 ± 59.7 months, p = 0.05). Asthma treatment was conducted according to the GINA guideline, and 18.4% (30 pts) of the patients were on allergen immunotherapy treatment. Significantly more uncontrolled patients were significantly more in Step 1 and 5 of treatment (p = 0.05 and p = 0.03). During the COVID-19 pandemic, patients in the GINA step 5 of treatment experienced a worsening of asthma, often twice as severe as compared to patients with asthma in GINA step 1–4. In these patients, even mild COVID-19 disease led to worsened asthma symptoms, while severe COVID-19 led to a severe asthma impairment measured by ACT score (p = 0.03) and VAS scale (p = 0.02), with increased oral corticosteroids consumption.

Conclusion

Maintaining optimal asthma control should be able to reduce risk of severe outcomes after COVID-19 disease. Communication via phone with the specialist involved in their asthma care was very comforting for patients, thus confirming the necessity to include phone calls, smart phone’s application or online evaluations and counseling in long-term care of chronic diseases.
Health insurance is associated with dental care use among university students in Washington State
Authors: Hill Courtney M. , Kerr Darragh , Chi Donald L.
Published: January 2023

Background

The goal of this study was to examine the association of health insurance and preventive dental care use among university students.

Methods

This secondary analysis of cross-sectional data focused on students at University of Washington in Washington state (WA) who completed a health insurance survey in 2017 (n = 3768). The exposure was health insurance (private insurance in WA [reference group], not insured, Medicaid or Medicare [public insurance], university insurance, private insurance not in WA, other) and the outcome was receiving a dental cleaning in the past 6 months. Logistic regression was used to generate odds ratios and 95% confidence intervals (CI) adjusted for confounders.

Results

About 5% of university students did not have health insurance and 37% did not have a dental cleaning in the past 6 months. Compared to students with private health insurance based in WA, the odds of not receiving a dental cleaning were 3.90 times greater for university students with no health insurance (95% CI 2.74, 5.55; p < .001) and 3.08 times greater for publicly-insured university students (95% CI 2.52, 3.76; p < .001).

Conclusions

University students are at risk for poor oral health behaviors. Those without health insurance and those with public insurance face barriers to preventive dental care. Efforts should be made to connect uninsured university students with insurance, dental services, and other oral health promotion activities.
Impact of insecticide resistance on malaria vector competence: a literature review
Authors: Suh Pierre Fongho , Elanga-Ndille Emmanuel , Tchouakui Magellan , Sandeu Maurice Marcel , Tagne Darus , Wondji Charles , Ndo Cyrille
Published: January 2023

Since its first report in Anopheles mosquitoes in 1950s, insecticide resistance has spread very fast to most sub-Saharan African malaria-endemic countries, where it is predicted to seriously jeopardize the success of vector control efforts, leading to rebound of disease cases. Supported mainly by four mechanisms (metabolic resistance, target site resistance, cuticular resistance, and behavioural resistance), this phenomenon is associated with intrinsic changes in the resistant insect vectors that could influence development of invading Plasmodium parasites. A literature review was undertaken using Pubmed database to collect articles evaluating directly or indiretly the impact of insecticide resistance and the associated mechanisms on key determinants of malaria vector competence including sialome composition, anti-Plasmodium immunity, intestinal commensal microbiota, and mosquito longevity. Globally, the evidence gathered is contradictory even though the insecticide resistant vectors seem to be more permissive to Plasmodium infections. The actual body of knowledge on key factors to vectorial competence, such as the immunity and microbiota communities of the insecticide resistant vector is still very insufficient to definitively infer on the epidemiological importance of these vectors against the susceptible counterparts. More studies are needed to fill important knowledge gaps that could help predicting malaria epidemiology in a context where the selection and spread of insecticide resistant vectors is ongoing.
A pH-responsive metal-organic framework for the co-delivery of HIF-2α siRNA and curcumin for enhanced therapy of osteoarthritis
Authors: Zhang Zi-Jian , Hou Ying-Ke , Chen Ming-Wa , Yu Xue-Zhao , Chen Si-Yu , Yue Ya-Ru , Guo Xiong-Tian , Chen Jin-Xiang , Zhou Quan
Published: January 2023

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH2. Our vitro tests showed that MIL-101-NH2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.
Impacts of the preceding cancer-specific health-related quality of life instruments on the responses to the subsequent EQ-5D-5L
Authors: Izumi Shoki , Hagiwara Yasuhiro , Matsuyama Yutaka , Shiroiwa Takeru , Taira Naruto , Kawahara Takuya , Konomura Keiko , Noto Shinichi , Fukuda Takashi , Shimozuma Kojiro
Published: January 2023

Background

In clinical studies, the EQ-5D-5L is often employed with disease-specific health-related quality of life instruments. The questions in the former are more general than the latter; however, it is known that responses to general questions can be influenced by preceding specific questions. Thus, the responses to the EQ-5D-5L have the possibility of being influenced by the preceding disease-specific health-related quality of life instruments. This may lead to bias in the cost-effectiveness analysis results. Therefore, this study aimed to evaluate the impact of the preceding cancer-specific health-related quality of life instruments on the EQ-5D-5L responses.

Methods

We prepared questionnaire booklets containing the EQ-5D-5L, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Functional Assessment of Cancer Therapy General with different orders. Using a quasi-randomized design, they were distributed to the patients undergoing drug therapy for advanced cancer, who were classified into three groups: Groups 1, 2, and 3 (the EQ-5D-5L placed first, second, and last, respectively). We compared the EQ-5D-5L index and the missingness of EQ-5D-5L among the groups.

Results

The mean EQ-5D-5L index was 0.796, 0.760, and 0.789 for groups 1 (n = 300), 2 (n = 306), and 3 (n = 331), respectively. The difference between Groups 2 and 1 was − 0.036 (95% CI − 0.065 to − 0.007; p = 0.015). The proportion of patients with an incomplete EQ-5D-5L was 0.11, 0.11, and 0.05 for Groups 1, 2, and 3, respectively. The difference of the proportions between group 3 and 1 and between 3 and 2 was − 0.06 (95% CI − 0.10 to − 0.02; p = 0.003) and − 0.06 (95% CI − 0.10 to − 0.02; p = 0.003), respectively.

Conclusions

Although the EQ-5D-5L index differed according to the instrument orders, the difference size would not be considerably larger than the minimally important difference. The patients tended to complete the EQ-5D-5L when they were placed at the end of the questionnaire.
The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: likely intersectionality with other neurological conditions
Authors: Parthasarathy Geetha , Pattison Melissa B. , Midkiff Cecily C.
Published: January 2023

Background

Lyme neuroborreliosis, caused by the bacterium Borrelia burgdorferi affects both the central and peripheral nervous systems (CNS, PNS). The CNS manifestations, especially at later stages, can mimic/cause many other neurological conditions including psychiatric disorders, dementia, and others, with a likely neuroinflammatory basis. The pathogenic mechanisms associated with Lyme neuroborreliosis, however, are not fully understood.

Methods

In this study, using cultures of primary rhesus microglia, we explored the roles of several fibroblast growth factor receptors (FGFRs) and fibroblast growth factors (FGFs) in neuroinflammation associated with live B. burgdorferi exposure. FGFR specific siRNA and inhibitors, custom antibody arrays, ELISAs, immunofluorescence and microscopy were used to comprehensively analyze the roles of these molecules in microglial neuroinflammation due to B. burgdorferi.

Results

FGFR1-3 expressions were upregulated in microglia in response to B. burgdorferi. Inhibition of FGFR 1, 2 and 3 signaling using siRNA and three different inhibitors showed that FGFR signaling is proinflammatory in response to the Lyme disease bacterium. FGFR1 activation also contributed to non-viable B. burgdorferi mediated neuroinflammation. Analysis of the B. burgdorferi conditioned microglial medium by a custom antibody array showed that several FGFs are induced by the live bacterium including FGF6, FGF10 and FGF12, which in turn induce IL-6 and/or CXCL8, indicating a proinflammatory nature. To our knowledge, this is also the first-ever described role for FGF6 and FGF12 in CNS neuroinflammation. FGF23 upregulation, in addition, was observed in response to the Lyme disease bacterium. B. burgdorferi exposure also downregulated many FGFs including FGF 5, 7, 9, 11, 13, 16, 20 and 21. Some of the upregulated FGFs have been implicated in major depressive disorder (MDD) or dementia development, while the downregulated ones have been demonstrated to have protective roles in epilepsy, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, blood–brain barrier stability, and others.

Conclusions

In this study we show that FGFRs and FGFs are novel inducers of inflammatory mediators in Lyme neuroborreliosis. It is likely that an unresolved, long-term (neuro)-Lyme infection can contribute to the development of other neurologic conditions in susceptible individuals either by augmenting pathogenic FGFs or by suppressing ameliorative FGFs or both.
Development of an assay system for the analysis of host RISC activity in the presence of a potyvirus RNA silencing suppressor, HC-Pro
Authors: Hong Syuan-Fei , Fang Ru-Ying , Wei Wei-Lun , Jirawitchalert Supidcha , Pan Zhao-Jun , Hung Yu-Ling , Pham Thanh Ha , Chiu Yen-Hsin , Shen Tang-Long , Huang Chien-Kang , Lin Shih-Shun
Published: January 2023

Background

To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR.

Methods

Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency.

Results

Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity.

Conclusions

In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.
Achieving long-term goals through early personalized management of schizophrenia: expert opinion on the role of a new fast-onset long-acting injectable antipsychotic
Authors: Vita Antonio , Fagiolini Andrea , Maina Giuseppe , Mencacci Claudio , Spina Edoardo , Galderisi Silvana
Published: January 2023

Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient’s characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.
Circular RNA hsa_circ_0075323 promotes glioblastoma cells proliferation and invasion via regulation of autophagy
Authors: Zhang Wenrui , Shi Zhonggang , Chen Shouren , Shen Shaoshan , Tu Songjie , Yang Jian , Qiu Yongming , Lin Yingying , Dai Xuejun
Published: January 2023

Background

Protein p62 (sequestosome 1) encoded by gene SQSTM1 plays a vital role in mediating protectively selective autophagy in tumor cells under stressed conditions. CircSQSTM1 (hsa_circ_0075323) is a circular transcript generated from gene SQSTM1 (chr5:179260586–179260782) by back-splicing. However, the potential role of hsa_hsa_circ_0075323 in glioblastoma (GBM) remains unclear. Here, we aimed to explore the biological function of hsa_circ_0075323 in GBM and its relationship with autophagy regulation.

Results

Hsa_circ_0075323 is highly expressed in GBM cells and mainly locates in the cytoplasm. Inhibition of hsa_circ_0075323 in U87-MG and T98G cells attenuated proliferation and invasion ability significantly, while upregulation of has_ circ_0075323 enhanced proliferation and migration of U251-MG and A172 cells. Mechanistically, depletion of hsa_circ_0075323 in GBM cells resulted in impaired autophagy, as indicated by increased expression of p62 and decreased expression of LC3B.

Conclusions

Hsa_circ_0075323 regulates p62-mediated autophagy pathway to promote GBM progression and may serve as a prognostic biomarker potentially.
Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation
Authors: Zang Chengwu , Xian Hang , Zhang Hang , Che Min , Chen Yongxiang , Zhang Fanliang , Cong Rui
Published: January 2023

Objective

To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects.

Methods

From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed.

Results

A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05).

Conclusions

The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.
Study of the accuracy of a radial arterial pressure waveform cardiac output measurement device after cardiac surgery
Authors: Ordoñez-Rufat Pilar , Mancho-Fora Nuria , Tebe-Cordomi Cristian , Polit-Martinez Victoria , Abellan-Lencina Ricardo , Fernandez-Alvarez Joaquin , Lopez-Delgado Juan Carlos
Published: January 2023

Background

Less invasive monitoring, such as radial arterial pulse contour analysis (ProAQT® sensor), represents an alternative when hemodynamic monitoring is necessary to guide postoperative management and invasive monitoring is not technically feasible. The aim of the study is to evaluate the accuracy of the ProAQT® sensor cardiac output measurements in comparison with Pulmonary Artery Catheter (PAC) during the postoperative course of patients who underwent cardiac surgery with cardiopulmonary bypass.

Case presentation

Prospective observational study in a Surgical Intensive Care Unit of a tertiary university hospital. Ten patients with a mean age of 73.5 years were included. The main comorbidities were hypertension, diabetes, dyslipidemia and the preoperative left ejection fraction was 43.8 ± 14.5%. Regarding the type of surgery, six patients underwent valve surgery, two underwent coronary artery bypass grafting and two underwent aortic surgery. The cardiac index measured simultaneously by the ProAQT® sensor was compared with the PAC. The parameters were evaluated at predefined time points during the early postoperative courses (6 h, 12 h, 24 h, 48 h and 72 h). The degree of agreement with the cardiac index between the PAC and the ProAQT® sensor along the time points was measured using the concordance correlation coefficient, Bland–Altman analysis, and four-quadrant plot. Sixty-three pairs of measurements were analyzed. We showed that measurements of cardiac index were slightly higher with PAC (β ̂ = − 0.146, p-value = 0.094). The concordance correlation coefficient for the additive model of cardiac index was 0.64 (95% Confidence Interval: 0.36, 0.82), indicating a high concordance between both sensors. Bland-Altmann analysis showed a mean bias of 0.45 L·min−1·m−2, limits of agreement from − 1.65 to 2.3 L·min−1·m−2, and percentage of error was 82.5%. Four-quadrant plot of changes in cardiac index showed a good concordance rate (75%), which increases after applying the exclusion zone (87%).

Conclusions

In patients undergoing cardiac surgery, the ProAQT® sensor may be useful to monitor cardiac index during the postoperative period, especially when more invasive monitoring is not possible.
Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis
Authors: Pramparo Tiziano , Steiner Robert D. , Rodems Steve , Jenkinson Celia
Published: January 2023

Background

Cerebrotendinous xanthomatosis (CTX) is a rare recessive genetic disease characterized by disruption of bile acid synthesis due to inactivation of the CYP27A1 gene. Treatment is available in the form of bile acid replacement. CTX is likely underdiagnosed, and prevalence estimates based on case diagnosis are probably inaccurate. Large population-based genomic databases are a valuable resource to estimate prevalence of rare recessive diseases as an orthogonal unbiased approach building upon traditional epidemiological studies.

Methods

We leveraged the Hardy–Weinberg principle and allele frequencies from gnomAD to calculate CTX prevalence. ClinVar and HGMD were used to identify high-confidence pathogenic missense variants and to calculate a disease-specific cutoff. Variant pathogenicity was also assessed by the VarSome implementation of the ACMG/AMP algorithm and the REVEL in silico predictor.

Results

CTX prevalence estimates were highest in Asians (1:44,407–93,084) and lowest in the Finnish population (1:3,388,767). Intermediate estimates were found in Europeans, Americans, and Africans/African Americans (1:70,795–233,597). The REVEL-predicted pathogenic variants accounted for a greater increase in prevalence estimates for Europeans, Americans, and Africans/African Americans compared with Asians. We identified the most frequent alleles designated pathogenic in ClinVar (p.Gly472Ala, p.Arg395Cys), labeled pathogenic based on sequence consequence (p.Met1?), and predicted to be pathogenic by REVEL (p.Met383Lys, p.Arg448His) across populations. Also, we provide a prospective geographic map of estimated disease distribution based on CYP27A1 variation queries performed by healthcare providers from selected specialties.

Conclusions

Prevalence estimates calculated herein support and expand upon existing evidence indicating underdiagnosis of CTX, suggesting that improved detection strategies are needed. Increased awareness of CTX is important for early diagnosis, which is essential for patients as early treatment significantly slows or prevents disease progression.
Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation
Authors: Yang Jianming , Chen Yewu , Sun Haobin , Zhang Xijian , Wang Jianfeng , Liang Zhixing , Fu Binsheng , Zhang Tong , Yi Shuhong , Deng Yinan , Yang Yang
Published: January 2023

Background

Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC.

Method

We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses.

Result

Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14–0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade.

Conclusion

Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.
Payload diversification: a key step in the development of antibody–drug conjugates
Authors: Conilh Louise , Sadilkova Lenka , Viricel Warren , Dumontet Charles
Published: January 2023

Antibody–drug conjugates (ADCs) is a fast moving class of targeted biotherapeutics that currently combines the selectivity of monoclonal antibodies with the potency of a payload consisting of cytotoxic agents. For many years microtubule targeting and DNA-intercalating agents were at the forefront of ADC development. The recent approval and clinical success of trastuzumab deruxtecan (Enhertu®) and sacituzumab govitecan (Trodelvy®), two topoisomerase 1 inhibitor-based ADCs, has shown the potential of conjugating unconventional payloads with differentiated mechanisms of action. Among future developments in the ADC field, payload diversification is expected to play a key role as illustrated by a growing number of preclinical and clinical stage unconventional payload-conjugated ADCs. This review presents a comprehensive overview of validated, forgotten and newly developed payloads with different mechanisms of action.
Present and future of telemedicine for pediatric care: an Italian regional experience
Authors: Zuccotti Gianvincenzo , Calcaterra Valeria , Foppiani Andrea
Published: January 2023

Telemedicine has been recognized as an integral part of the National Health Service in Italy. Telemedicine can be adopted in the diagnostic therapeutic assistance pathway and in individual assistance plans. In the region of Lombardy, home care models from the perspective of the project of a public virtual hospital have been introduced. A regional operational center was proposed to ensure continuing care utilising organizational and technological solutions to deliver healthcare services remotely, with high quality standards, a positive economic impact and user friendly services for both the user and the professional. In the field of pediatrics telemedicine was also introduced at the Vittore Buzzi Children’ Hospital, in Milan, the capital of the region of Lombardy. These included routine pediatric hospital activities and innovative programs, such as early discharge, telecardiology, online supervised exercise training and preventive healthcare. Telehealth represents the evolution of health care delivery systems to adapt to new technology and the needs of the pediatric population, offering a strategic system to invest in children’s health.
Differential paired stage-specific expression of Babesia bovis cysteine-rich GCC2/GCC3 domain family proteins (BboGDP) during development within Rhipicephalus microplus
Authors: Hussein Hala E. , Johnson Wendell C. , Ueti Massaro W.
Published: January 2023

Background

Babesia bovis, an intra-erythrocytic apicomplexan parasite, is one of the causative agents of bovine babesiosis, the most important tick-borne disease of cattle in tropical and subtropical regions. Babesia bovis has a complex life-cycle that includes sexual development within the tick vector. The development of a transmission blocking vaccine to control bovine babesiosis requires the identification of antigens displayed on the surface of the parasite during its development within tick vectors. Four B. bovis cysteine-rich GCC2/GCC3 domain protein (BboGDP) family members were previously identified and are differentially expressed as discrete pairs by either blood stages or kinetes. In this study we focused on two family members, BboGDP1 and -3, that are expressed by Babesia parasites during tick infection.

Methods and results

Transcription analysis using quantitative PCR demonstrated that BboGDP1 and -3 were upregulated in in vitro-induced sexual stage parasites and during parasite development in the tick midgut. Moreover, protein expression analysis of BboGDP1 and -3 during the development of sexual stages in in vitro culture was consistent with their transcription profile. Live immunofluorescence analysis using polyclonal antibodies confirmed surface expression of BboGDP1 and -3 on in vitro-induced sexual stage parasites. In addition, fixed immunofluorescence analysis showed reactivity of anti-BboGDP1 and -3 polyclonal antibodies to kinetes.

Conclusions

The collective data indicate that BboGDP1 and -3 are expressed by kinetes and on the surface of sexual stages of the parasites. The identified parasite surface membrane proteins BboGDP1 and -3 are potential candidates for the development of a B. bovis transmission blocking vaccine.

Graphical Abstract
Beauveria bassiana interacts with gut and hemocytes to manipulate Aedes aegypti immunity
Authors: de Oliveira Barbosa Bitencourt Ricardo , Corrêa Thaís Almeida , Santos-Mallet Jacenir , Santos Huarrisson Azevedo , Lowenberger Carl , Moreira Haika Victória Sales , Gôlo Patrícia Silva , Bittencourt Vânia Rita Elias Pinheiro , da Costa Angelo Isabele
Published: January 2023

Background

Mosquito-borne diseases affect millions of people. Chemical insecticides are currently employed against mosquitoes. However, many cases of insecticide resistance have been reported. Entomopathogenic fungi (EPF) have demonstrated potential as a bioinsecticide. Here, we assessed the invasion of the EPF Beauveria bassiana into Aedes aegypti larvae and changes in the activity of phenoloxidase (PO) as a proxy for the general activation of the insect innate immune system. In addition, other cellular and humoral responses were evaluated.

Methods

Larvae were exposed to blastospores or conidia of B. bassiana CG 206. After 24 and 48 h, scanning electron microscopy (SEM) was conducted on the larvae. The hemolymph was collected to determine changes in total hemocyte concentration (THC), the dynamics of hemocytes, and to observe hemocyte-fungus interactions. In addition, the larvae were macerated to assess the activity of PO using L-DOPA conversion, and the expression of antimicrobial peptides (AMPs) was measured using quantitative Real-Time PCR.

Results

Propagules invaded mosquitoes through the midgut, and blastopores were detected inside the hemocoel. Both propagules decreased the THC regardless of the time. By 24 h after exposure to conidia the percentage of granulocytes and oenocytoids increased while the prohemocytes decreased. By 48 h, the oenocytoid percentage increased significantly (P < 0.05) in larvae exposed to blastospores; however, the other hemocyte types did not change significantly. Regardless of the time, SEM revealed hemocytes adhering to, and nodulating, blastospores. For the larvae exposed to conidia, these interactions were observed only at 48 h. Irrespective of the propagule, the PO activity increased only at 48 h. At 24 h, cathepsin B was upregulated by infection with conidia, whereas both propagules resulted in a downregulation of cecropin and defensin A. At 48 h, blastospores and conidia increased the expression of defensin A suggesting this may be an essential AMP against EPF.

Conclusion

By 24 h, B. bassiana CG 206 occluded the midgut, reduced THC, did not stimulate PO activity, and downregulated AMP expression in larvae, all of which allowed the fungus to impair the larvae to facilitate infection. Our data reports a complex interplay between Ae. aegypti larvae and B. bassiana CG 206 demonstrating how this fungus can infect, affect, and kill Ae. aegypti larvae.

Graphical Abstract
Estimates and trends of the global burden of NASH-related liver cancer attributable to high fasting plasma glucose in 1990–2019: analysis of data from the 2019 Global Burden of Disease Study
Authors: Li Ziyi , Yang Na , He Liyun , Wang Jialu , Ping Fan , Li Wei , Xu Lingling , Zhang Huabing , Li Yuxiu
Published: January 2023

Background

Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide.

Methods

The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman’s rank-order correlation.

Results

Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48–0.89), and 0.30 (95% UI 0.05–0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23–2.18]; death 0.05 [95% UI 0.01–0.11]).

Conclusion

The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.