bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoplasmic aggregation of mutant FUS causes multistep RNA splicing perturbations in the course of motor neuron pathology
Authors: Rezvykh Alexander P , Ustyugov Aleksey A , Chaprov Kirill D , Teterina Ekaterina V , Nebogatikov Vladimir O , Spasskaya Daria S , Evgen’ev Michael B , Morozov Alexey V , Funikov Sergei Yu
Published: April 2023

Dysfunction of the RNA-binding protein (RBP) FUS implicated in RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Mutations affecting FUS nuclear localization can drive RNA splicing defects and stimulate the formation of non-amyloid inclusions in affected neurons. However, the mechanism by which FUS mutations contribute to the development of ALS remains uncertain. Here we describe a pattern of RNA splicing changes in the dynamics of the continuous proteinopathy induced by mislocalized FUS. We show that the decrease in intron retention of FUS-associated transcripts represents the hallmark of the pathogenesis of ALS and is the earliest molecular event in the course of progression of the disease. As FUS aggregation increases, the pattern of RNA splicing changes, becoming more complex, including a decrease in the inclusion of neuron-specific microexons and induction of cryptic exon splicing due to the sequestration of additional RBPs into FUS aggregates. Crucially, the identified features of the pathological splicing pattern are also observed in ALS patients in both sporadic and familial cases. Our data provide evidence that both a loss of nuclear FUS function due to mislocalization and the subsequent cytoplasmic aggregation of mutant protein lead to the disruption of RNA splicing in a multistep fashion during FUS aggregation.
Kidney and urinary tract involvement in systemic mastocytosis
Authors: Bharati Joyita , Shah Nikita , Desai Ankuri , Gladstone Douglas , Krushna Das Chandan , Nieto Maria Jacqueline , Jhaveri Kenar D , Izzedine Hassan
Published: April 2023

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) such as mesangioproliferative GN, membranous nephropathy and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.
Cosmological gravity probes: Connecting recent theoretical developments to forthcoming observations
Authors: Arai Shun , Aoki Katsuki , Chinone Yuji , Kimura Rampei , Kobayashi Tsutomu , Miyatake Hironao , Yamauchi Daisuke , Yokoyama Shuichiro , Akitsu Kazuyuki , Hiramatsu Takashi , Hirano Shin’ichi , Kase Ryotaro , Katsuragawa Taishi , Kobayashi Yosuke , Namikawa Toshiya , Nishimichi Takahiro , Okumura Teppei , Shiraishi Maresuke , Shirasaki Masato , Sunayama Tomomi , Takahashi Kazufumi , Taruya Atsushi , Tokuda Junsei
Published: April 2023

Since the discovery of the accelerated expansion of the present universe, significant theoretical developments have been made in the area of modified gravity. In the meantime, cosmological observations have been providing more high-quality data, allowing us to explore gravity on cosmological scales. To bridge the recent theoretical developments and observations, we present an overview of a variety of modified theories of gravity and the cosmological observables in the cosmic microwave background and large-scale structure, supplemented with a summary of predictions for cosmological observables derived from cosmological perturbations and sophisticated numerical studies. We specifically consider scalar–tensor theories in the Horndeski and DHOST family, massive gravity/bigravity, vector–tensor theories, metric-affine gravity, and cuscuton/minimally modified gravity, and discuss the current status of those theories with emphasis on their physical motivations, validity, appealing features, the level of maturity, and calculability. We conclude that the Horndeski theory is one of the most well-developed theories of modified gravity, although several remaining issues are left for future observations. The paper aims to help to develop strategies for testing gravity with ongoing and forthcoming cosmological observations.
Quantum mechanical calculations of synchro-curvature radiations: maser possibility
Authors: Tomoda Hiroko , Yamada Shoichi
Published: April 2023

We calculate the radiative transition rates for synchro-curvature radiation to explore the possibility of maser in the environment that may occur in the magnetosphere of neutron stars (NSs). Unlike previous studies, we employ relativistic quantum mechanics, solving the Dirac equation for an electron in helical magnetic fields. Following Voisin et al. [1,2], we utilize adiabatic spinor rotations, under the assumption that the curvature of magnetic-field lines is much larger than the Larmor radius, to obtain the wave functions of an electron. We classify the electron states either by the spin operator projected on the magnetic field or by the helicity operator. To demonstrate that there is a regime where the true absorption rate becomes negative, we numerically evaluate the obtained formulae for some parameter values that may be encountered in the outer gaps of different types of NSs. We show that there is indeed a range of parameters for the negative true absorption rate to occur. We will also study the dependence on those parameters systematically and discuss the classical limit of our formulae. We finally give a crude estimate of the amplification factor in the same environment.
Dress code for infrared safe scattering in QED
Authors: Hirai Hayato , Sugishita Sotaro
Published: April 2023

We study the S-matrix and inclusive cross-section for general dressed states in quantum electrodynamics. We obtain an infrared factorization formula of the S-matrix elements for general dressed states. This enables us to study which dressed states lead to infrared-safe S-matrix elements. The condition for dressed states can be interpreted as the memory effect, which is nothing but the conservation law of the asymptotic symmetry. We derive the generalized soft photon theorem for general dressed states. We also compute an inclusive cross-section using general dressed states. It is necessary to use appropriate initial and final dressed states to evaluate interference effects, which cannot be computed correctly by using Fock states due to the infrared divergence.
Codelivery of dihydroartemisinin and chlorin e6 by copolymer nanoparticles enables boosting photodynamic therapy of breast cancer with low-power irradiation
Authors: Jia Jing , Chen Wenping , Xu Long , Wang Xuewen , Li Min , Wang Bin , Huang Xiangyu , Wang Tao , Chen Yang , Li Mengdie , Tian Dan , Zhuang Junyang , Lin Xinhua , Li Ning
Published: April 2023

Given that chemotherapy as a stand-alone therapeutic strategy may not be sufficient to effectively treat cancer, there is increasing interest in combination of chemotherapy and alternative therapies. Photodynamic therapy has the advantages of high selectivity and low side effects, so the combination of photodynamic therapy and chemotherapy has become one of the most appealing strategies for tumor treatment. In this work, we constructed a nano drug codelivery system (PPDC) to realize the combined treatment of chemotherapy and photodynamic therapy through encapsulating chemotherapeutic drug dihydroartemisinin and photosensitizer chlorin e6 in PEG-PCL. The potentials, particle size and morphology of nanoparticles were characterized by dynamic light scattering and transmission electron microscopy. We also investigated the reactive oxygen species (ROS) generation and drug release ability. The antitumor effect in vitro was investigated by methylthiazolyldiphenyl-tetrazolium bromide assays and cell apoptosis experiments, and the potential cell death mechanisms were explored by ROS detection and Western blot analysis. The in vivo antitumor effect of PPDC was evaluated under the guidance of fluorescence imaging. Our work provides a potential antitumor treatment approach and expands the application of dihydroartemisinin for breast cancer therapy.
The Direct and Long-Term Effects of Raloxifene as Adjunctive Treatment for Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Clinical Trial
Authors: Brand Bodyl A , de Boer Janna N , Marcelis Machteld C , Grootens Koen P , Luykx Jurjen J , Sommer Iris E
Published: April 2023

Background and hypothesis

Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD.

Study design

This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned 1:1 to 12-week add-on raloxifene or placebo. Primary outcomes were symptom severity at 6, 12, and 38 weeks and cognition at 12 and 38 weeks, as measured with the Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia, respectively. Intention-to-treat analyses were performed using linear mixed-effect models.

Study results

We assessed 261 patients for eligibility, of which 102 (28% female) were assigned to raloxifene (n = 52) or placebo (n = 48). Although we found no main effect of raloxifene, secondary sex-specific analysis showed that in women, raloxifene had beneficial effects on negative symptoms at week 6 (LSM −2.92; adjusted P = 0.020) and week 12 (LSM −3.12; adjusted P = 0.030), and on working memory at week 38 (LSM 0.73; adjusted P = 0.040), while having negative effects on working memory at week 38 in men (LSM −0.53; adjusted P = 0.026). The number of adverse events was similar between groups.

Conclusions

Our results do not support the use of raloxifene in patients with SSD in general, but suggest female-specific beneficial effects of raloxifene on negative symptoms and working memory. Our findings encourage further research on sex-specific pharmacotherapeutic treatment.
Complexities and Nuances in Radical Right Voters’ (Anti)Feminism
Authors: Off Gefjon
Published: April 2023

While radical right parties commonly advance conservative gender positions, research on radical right voters’ gender attitudes remains inconclusive. To understand radical right voters’ gender attitudes, I first analyze previous research for frames that antifeminist actors commonly use to advance their arguments. I then draw on interviews with eastern German radical right voters to analyze whether and how these voters apply antifeminist frames to argue about feminist policy. I demonstrate that they use antifeminist frames to oppose mostly third-wave and recently salient feminist issues, but also support certain feminist policies, sometimes for instrumental reasons. Further, voters include particularities of their context in their arguments. Eastern Germany constitutes an atypical context, allowing for insights into voters’ (anti)feminism in a post-socialist context marked by atheism and relatively advanced gender norms. The study contributes to understanding complexities and nuances in radical right voters’ gender attitudes, and thereby to understanding cultural grievances beyond anti-immigration attitudes.
Polystyrene nanoplastics exacerbated Pb-induced liver toxicity in mice
Authors: Yuan Hongbin , Wen Siyue , Zhao Yu , Hu Liehai , Xu Hengyi
Published: April 2023

Nanoplastics are widely distributed in the environment and can adsorb heavy metals, which poses a potential threat to human health through food chain. It is necessary to assess the combined toxicity of nanoplastics and heavy metals. The adverse effect of Pb and nanoplastics on liver, single or in combination, was evaluated in this study. The results showed that the Pb content in co-exposure group of nanoplastics and Pb (PN group) was higher than the group exposed to Pb alone (Pb group). And more severe inflammatory infiltration was observed in liver sections of PN group. The level of inflammatory cytokines and malondialdehyde were increased, while the superoxide dismutase activity was decreased in liver tissues of PN group. Moreover, the gene expression level of nuclear factor-erythroid 2-related factor 2, nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 and catalase, which is related to antioxidation, was downregulated. And the expression level of cleaved-Caspase9 and cleaved-Caspase3 were increased. However, with the supplementation of oxidative stress inhibitor N-Acetyl-L-cysteine, liver damage shown in PN group was evidently alleviated. In summary, nanoplastics evidently exacerbated the deposition of Pb in liver and potentially aggravated the Pb-induced liver toxicity by activating oxidative stress.
Fetal and neonatal dioxin exposure causes sex-specific metabolic alterations in mice
Authors: Hoyeck Myriam P , Merhi Rayanna C , Tulloch Cameron , McCormick Kaitlyn , Mohammed Abu Hossain Shahen , Hanson Antonio A , Bruin Jennifer E
Published: April 2023

Epidemiological studies report associations between early-life exposure to persistent organic pollutants (POPs) and impaired metabolic homeostasis in adulthood. We investigated the impact of early-life exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or ‘dioxin’) on the establishment of β-cell area during the perinatal period, as well as β-cell health and glucose homeostasis later in life. Adult female mice were injected with either corn oil (CO; vehicle control) or TCDD (20 ng/kg/day) 2×/week throughout mating, pregnancy, and lactation; offspring were thus indirectly exposed to maternal TCDD in utero and during lactation, with pollutant exposure ending at weaning. All offspring were maintained on chow diet from weaning until 12–17 weeks of age, after which a subset of CO- and TCDD-exposed offspring were transferred to a 45% high fat diet (HFD) as a metabolic stressor for an additional 10 weeks. TCDD significantly upregulated cytochrome P450 1a1 (Cyp1a1) gene expression in offspring pancreas at birth and weaning, indicating that maternal TCDD directly reaches the developing pancreas. TCDD-exposed pups were transiently hypoglycemic at birth and females were born with reduced % β-cell area, which persisted into adulthood. Early-life TCDD exposure had no persistent long-term effects on glucose homeostasis in chow-fed offspring, but when transferred to HFD, TCDD-exposed female offspring had a delayed onset of HFD-induced hyperglycemia, more pronounced HFD-induced hyperinsulinemia, and increase % PCNA+ β-cells compared with CO-exposed female offspring. This study demonstrates that early-life exposure of mice to TCDD has modest effects on metabolic health in chow-fed offspring but alters metabolic adaptability to HFD feeding in females.
Orobanche crenata: A Bibliometric Analysis of a Noxious Parasitic Plant
Authors: El Amri Majda , Khayi Slimane , Triqui Zine El Abidine , Amri Moez , Mentag Rachid
Published: April 2023

Orobanche crenata is a parasitic weed representing a serious constraint to crop production in the Mediterranean basin. Here, we aim to evaluate the global scientific research status and trends of O. crenata through a bibliometric analysis to identify prominent research themes, development trends, and major contributors in terms of authors, institutions, countries, and journals. In the span of 53 years, from 1968 to 2021, 274 articles related to this field were retrieved from Scopus database and were analyzed using VOSviewer and BiblioShiny software. Results showed that 70.4% of all articles on O. crenata have been published in the last two decades. “Control methods” was the most prevalent research theme with 55.9% of all articles. Weed Research is the most influential journal. The countries with the highest number of articles were Spain, Egypt, and Italy. The Institute for Sustainable Agriculture is the most involved institution, contributing to 31.7% of all articles, and authors from Spain were the most productive. The latest research literature (5 years) was performed mainly by authors from Spain, Morocco, and Tunisia, emphasizing the persistence of this constraint in these countries. Keyword analysis revealed that “Vicia faba”, “germination”, and “legumes” are the most researched hotspots. Despite the growing collaborative behavior in this area, cooperation between countries is still deficient and should be extended to countries that are recently affected by this scourge to exchange expertise already acquired by experienced researchers, thus allowing better worldwide control of this parasitic weed.
Auto-immune hemolytic anemia and hemophagocytic lymphohistiocytosis as immune-related adverse event in patients with metastatic melanoma and concurrent chronic lymphocytic leukemia: a case series and literature review
Authors: Dirven Iris , Vander Mijnsbrugge An-Sofie , Mignon Sacha , Tijtgat Jens , Kint Nicolas , Neyns Bart
Published: April 2023

Auto-immune hemolytic anemia (AIHA) and hemophagocytic lymphohistiocytosis (HLH) are both rare immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors. Consensus treatment guidelines are currently lacking. Patients with a solid malignancy and a concurrent lymphoproliferative disorder, such as chronic lymphocytic leukemia (CLL), might be more prone to develop hematological irAEs. We report the case history of two patients, diagnosed with CLL, who during treatment for metastatic melanoma with nivolumab, a PD-1 immune checkpoint blocking mAb, developed AIHA and HLH in combination with AIHA. Furthermore, we provide a review of the literature on published cases of immune-related AIHA and HLH and their correlation with CLL.
Efficacy and Safety of Picosecond Laser in the Treatment of Melasma: A Network Meta-analysis
Authors: Ren Rongxin , Bao Shiwei , Qian Wenjiang , Zhao Hongyi
Published: April 2023

BACKGROUND

The role of lasers in the treatment of melasma and acquired hyperpigmentation disease of the skin has been suggested by clinicians. However, there is no consensus on the most efficient and safe treatment method.

OBJECTIVE

To systematically evaluate the efficacy and safety of picosecond laser in the treatment of melasma.

METHODS and Materials

PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese scientific journal database, and Wanfang database were searched. The data for therapeutic efficacy, melasma area and severity score, and incidence rate of adverse reactions were extracted from the included studies.

RESULTS

A total of 20 studies involving 1,182 patients were included in this network meta-analysis. Combined therapy with carbamic acid and 1064-nm picosecond laser was the best measure. Melasma area and severity index score of patients after low-power fractional CO2 laser treatment was higher than that of patients after the treatment with 1064-nm picosecond laser.

CONCLUSION

Aminomethyl cyclic acid combined with 1064-nm picosecond laser may have the highest effective rate after treatment. Low-power fractional CO2 laser provided the lowest melasma area and severity index score after treatment, and the incidence rate of adverse reactions after treatment, was highest when intense pulsed light was used.
The Clinical Efficacy of Punch Excision Combined With Intralesional Steroid Injection for Keloid Treatment
Authors: Hou Shen , Chen Qian , Chen Xiao-Dong
Published: April 2023

BACKGROUND

Conservative and nonconservative treatments are available for keloids. However, few studies have explored the effectiveness of punch excision in keloid treatment.

OBJECTIVE

This study aimed to investigate the efficacy and safety of punch excision combined with intralesional steroid injection for keloid treatment.

METHODS

In this prospective, randomized, controlled trial, 81 patients were randomly divided into 2 groups. The patients in the treatment group were initially treated with punch excision combined with intralesional steroid injection, followed by injection treatment alone. The patients in the control group received intralesional steroid injection alone. The keloid thickness before and after the punch excision was evaluated; the keloid scores at different time points and the number of injection treatments required in both groups were compared, and adverse reactions were observed.

RESULTS

The mean thickness after punch excision was lower (p < .05), injection treatments were fewer (p < .05), keloid scores were significantly lower (p < .05), and incidence rate of long-term adverse effects was lower in the treatment group than in the control group (p < .05).

CONCLUSION

The combination of punch excision and intralesional steroid injection has a notable therapeutic effect on keloids, shortening the treatment course without evident adverse reactions.
Influence of VAC Therapy on Perfusion and Edema of Gracilis Flaps: Prospective Case-control Study
Authors: Kuenlen Anian , Waked Karl , Eisenburger Michael , Oramary Alan , Alsherawi Abeer , Ninkovic Milomir
Published: April 2023

Background:

The gracilis muscle flap is a popular choice in reconstructive surgery to repair soft tissue defects or for functional restoration. Little is known on the influence of postoperative application of VAC (vacuum-assisted closure; Kinetic Concepts Inc., San Antonio, Tex.) therapy on perfusion and postoperative flap edema of free gracilis muscle flaps.

Methods:

In total, 26 patients with soft tissue defects of lower extremity underwent gracilis muscle flap reconstruction. The study group (VAC, n = 13) was supplied with postoperative negative pressure therapy as a dressing; the control group (NVAC, n = 13) was supplied with conventional fat gauze dressing. Postoperative measurements of micro- and macroperfusion were performed intraoperatively, on postoperative day (POD) 3 and POD 5. Flap edema measurement was performed intraoperatively, on POD 5 and 2 weeks after operation.

Results:

The VAC group showed significantly better macroflow during intraoperative VAC treatment, as well on POD 3 and POD 5. Venous outflow was also better with lower hemoglobin levels. Microflow was better in the NVAC group with higher measured oxygen levels. All gracilis muscle flaps of the VAC group showed significantly less flap edema compared with the control group.

Conclusions:

VAC application on free gracilis muscle flaps leads to significantly less postoperative flap edema, improved arterial macroflow, and improved venous outflow. VAC therapy can be used without any danger for patient’s safety, as flap survival is not endangered, and presents an easy to handle and pleasant dressing regimen for nursing staff and patients.
Exercise characteristics and blood pressure reduction after combined aerobic and resistance training: a systematic review with meta-analysis and meta-regression
Authors: Schneider Vinícius M. , Domingues Lucas B. , Umpierre Daniel , Tanaka Hirofumi , Ferrari Rodrigo
Published: April 2023

Objective:

The purpose of this systematic review with meta-analysis was to determine the efficacy of combined aerobic and strength training in adults with hypertension and the influence of exercise training characteristics on blood pressure (BP) reduction.

Methods:

Randomized clinical trials of interventions involving combined aerobic and strength training versus nonexercise control groups (Control) in adults with hypertension were included. The literature search was conducted on PubMed, Cochrane Central, EMBASE, Scopus, and LILACS until December 2021. A random effects meta-analysis was performed using the mean difference in BP changes from baseline, comparing combined aerobic and strength training vs. Control as the effective measure. A multivariate meta-regression analysis was also performed to evaluate the relationship between exercise training characteristics and magnitudes of BP reductions.

Results:

Thirty-seven studies with 41 exercise interventions (1942 participants) were analyzed. The pooled mean differences with a 95% confidence interval (95% CI) showed significant reductions in SBP (−6.4 mmHg; 95% CI, −9.1 to −3.6) and DBP (−3.7 mmHg; 95% CI, −4.9 to −2.4). Meta-regression analysis revealed that greater exercise intensity and a greater number of sets in resistance training were associated with greater reductions in SBP. Greater exercise intensity was also associated with greater decreases in DBP.

Conclusion:

Combined aerobic and resistance training is an effective intervention in reducing both SBP and DBP in adults with hypertension, with greater hypotensive effects expected with higher intensity and more volume.
Expert consensus on the use of traditional Chinese medicine for the treatment of common symptoms of post COVID-19 short-term condition
Authors: Zhang Junhua , Pang Bo , Liu Qingquan , Zhang Hongchun , Zheng Wenke , Yang Fengwen , Pang Wentai , Jin Xinyao , Chao Enxiang , Zhang Boli ,   on behalf of the expert consensus working group.
Published: April 2023

A proportion of patients recovered from COVID-19 have ongoing, recurrent, or new symptoms after negative nucleic acid/antigen test results, which has become a new public health problem that needs to be concerned. Traditional Chinese medicine (TCM) has shown its unique advantages in preventing, treating, and rehabilitating COVID-19. To further standardize clinician’s clinical judgment and use of TCM for the treatment of common symptoms associated with COVID-19 infection following negative nucleic acid/antigen results, the front-line clinical experts were invited for discussion on the concepts, etiology, clinical manifestations of post COVID-19 condition, and considerations of treatment with TCM to form the consensus. Clinicians of TCM, Western medicine, or integration of both can use this consensus document for practice and research purposes.
The Relationship between Cancer and Radiation: A New Paradigm
Authors: Augustine Frank
Published: April 2023

A key concern with the use of radiation sources (including nuclear power) is the health effects of low levels of radiation, especially the regulatory assumption that every additional increment of radiation increases the risk of cancer (linear no-threshold model, or LNT). The LNT model is nearly a century old. There are dozens if not hundreds of studies showing that this model is incompatible with animal, cellular, molecular, and epidemiological data for low-dose rates in the range of both background radiation levels and much of occupational exposure. The assumption that every increment of radiation equally increases the risk of cancer results in increased physical risks to workers involved with actions to reduce radiation exposure (such as risks from welding additional shielding in place or from additional construction activities to reduce post-closure waste site radiation levels) and avoidance of medical exposure even when radiation treatment has a lower risk than other options such as surgery. One fundamental shortcoming of the LNT model is that it does not account for natural processes that repair DNA damage. However, there is no contiguous mathematical model that estimates cancer risk for both high- and low-dose rates that incorporates what we have learned about DNA repair mechanisms and is sufficiently simple and conservative to address regulatory concerns. The author proposes a mathematical model that dramatically reduces the estimated cancer risks for low-dose rates while recognizing the linear relationship between cancer and dose at high-dose rates.
Prediction of Diabetic Retinopathy Severity Using a Combination of Retinal Neurodegeneration and Capillary Nonperfusion on OCT Angiography
Authors: Kim Kiyoung , Kim Eung Suk , Yu Seung-Young
Published: April 2023

Purpose:

To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods:

A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3x3 mm2 and 12×12 mm2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages.

Results:

Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12×12 mm2 field in participants with early stage DR. Inferior hemispheric NPA of 12×12 mm2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12×12 mm2 and 3×3 mm2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%).

Conclusion:

A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occurs in midperipheral retina with macular neurodegeneration and progress posteriorly.
Evaluation of vision-related quality of life in patients after vitrectomy following idiopathic epiretinal membrane
Authors: Bajraktari Gentian , Jukić Tomislav , Vukojevic Nenad , Oroz Martin , Bertetić Andrea Radolović , Jashari Fisnik
Published: April 2023

Purpose:

To evaluate the impact of different intraocular tamponades on the visual-related quality of life (VRQOL) after idiopathic epiretinal membrane (IEM) surgery with epiretinal membrane peeling.

Methods:

We prospectively enrolled 50 patients diagnosed with IEM who underwent pars plana vitrectomy (PPV). Patients were consecutively assigned to either the air tamponade (air) group (25 patients) or the balanced salt solutions (BSS) tamponade group (25 patients). The following data were collected before and after surgery and compared between two groups: VRQOL, best corrected visual acuity (BCVA), intraocular pressure (IOP), metamorphopsia, contrast sensitivity (CS), and central macular thickness (CMT).

Results:

PPV was performed in 50 eyes. At baseline, there were no significant differences between the two groups. At 6 months postoperatively, VRQOL (p < 0.001), BCVA (p < 0.001), CMT (p < 0.001), CS (p < 0.001), and metamorphopsia (p < 0.001) improved significantly in comparison to baseline, without significant differences between the air tamponade and BSS groups.

Conclusion:

Removing IEM significantly improved visual function and VRQOL. Despite improvements, our study showed no difference postoperatively whether air or BSS tamponade was used during surgery. As a result, air tamponade may not be a mandatory treatment for IEM surgery and provides no additional advantage compare with BSS tamponade.
Antimicrobial Drug–Drug Interactions in the Treatment of Infectious Keratitis
Authors: Dunster Elianna , Johnson William L. , Wozniak Rachel A. F.
Published: April 2023

Purpose:

Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs.

Methods:

Using a panel of 9 ophthalmic antibiotics, 3 antifungal agents, and 2 antiacanthamoeba therapeutics, fractional inhibitory concentration testing in the standard checkerboard format was used to study 36 antibiotic–antibiotic combinations, 27 antibiotic–antifungal combinations, and 18 antibiotic–antiacanthamoeba combinations against bothStaphylococcus aureusandPseudomonas aeruginosafor synergistic, additive, neutral, or antagonistic drug–drug interactions.

Results:

We demonstrate that while most combinations resulted in no change in antimicrobial efficacy of individual components, the combination of erythromycin + polyhexamethylene biguanide was found to be antagonistic towardP. aeruginosa. Conversely, 18 combinations towardS. aureusand 15 combinations towardP. aeruginosaresulted in additive or synergistic activity, including 4 with improved activity toward both species.

Conclusions:

Understanding how drug–drug interactions may affect drug efficacy is critical to selecting the appropriate combination therapy and improving clinical outcomes of this blinding disease.
Peptidoglycan-induced modulation of metabolic and inflammatory responses
Authors: Wolf Andrea J.
Published: April 2023

Bacterial cell wall peptidoglycan is composed of innate immune ligands and, due to its important structural role, also regulates access to many other innate immune ligands contained within the bacteria. There is a growing body of literature demonstrating how innate immune recognition impacts the metabolic functions of immune cells and how metabolic changes are not only important to inflammatory responses but are often essential. Peptidoglycan is primarily sensed in the context of the whole bacteria during lysosomal degradation; consequently, the innate immune receptors for peptidoglycan are primarily intracellular cytosolic innate immune sensors. However, during bacterial growth, peptidoglycan fragments are shed and can be found in the bloodstream of humans and mice, not only during infection but also derived from the abundant bacterial component of the gut microbiota. These peptidoglycan fragments influence cells throughout the body and are important for regulating inflammation and whole-body metabolic function. Therefore, it is important to understand how peptidoglycan-induced signals in innate immune cells and cells throughout the body interact to regulate how the body responds to both pathogenic and nonpathogenic bacteria. This mini-review will highlight key research regarding how cellular metabolism shifts in response to peptidoglycan and how systemic peptidoglycan sensing impacts whole-body metabolic function.
PaCO2 Levels at Admission Influence the Prognosis of Sepsis Patients: A Nonlinear Relationship
Authors: Qu Zhongkai , Ye Yan , Li Fang , Ren Yinlong , Lu Fan , Li Longzhu , Lyu Jun , Yin Haiyan
Published: April 2023

Background:

Sepsis is a life-threatening organ dysfunction caused by a maladjusted host response to infection (Sequential Organ Failure Assessment [SOFA] ≥ 2). PaCO2 is a blood gas that is commonly tested in hospitalized patients. Few studies have investigated how abnormal PaCO2 levels influence the prognosis of sepsis patients.

Methods:

A retrospective study was applied to data on sepsis patients extracted from the MIMIC-III public database and the results of their first PaCO2 examination after admission. The outcome measure was all-cause death within 90 days of follow-up. The patients were divided into five quintile groups, and the relationship between PaCO2 and all-cause death in sepsis patients was studied using restricted cubic splines (RCSs).

Results:

Our study included 4898 sepsis patients, the hypocapnia (PaCO2 < 31 mmHg) and hypercapnia (PaCO2 ≥ 49 mmHg) groups were associated with the risk of death in sepsis patients using quintile grouping and the multivariate Cox model, with HRs of 1.12 (95% CI = 1.03–1.29) and 1.25 (95% CI = 1.10–1.41), respectively, when compared with the control group (37 ≤ PaCO2 < 41 mmHg). The relationship between PaCO2 and all-cause death in sepsis patients was U-shaped.

Conclusion:

The presence of hypercapnia and hypocapnia at the time of hospital admission will have adverse effects on all-cause death in sepsis patients.
Combination of psoas muscle mass index and neutrophil-to-lymphocyte ratio as a noninvasive prognostic marker in hepatocellular carcinoma patients undergoing radiofrequency ablation
Authors: Hayashi Manabu , Abe Kazumichi , Fujita Masashi , Takahashi Atsushi , Ohira Hiromasa
Published: April 2023

Aim

The psoas muscle index (PMI) and neutrophil-to-lymphocyte ratio (NLR) have been reported as useful noninvasive prognostic markers in patients with hepatocellular carcinoma (HCC). The usefulness of the combination of the PMI and NLR as a prognostic marker in HCC patients undergoing radiofrequency ablation (RFA) is unclear.

Methods

We retrospectively analyzed the PMI and NLR in 112 patients undergoing RFA, including 40 patients aged 75 years and older (36%). The influence of the PMI and NLR on disease-free survival and overall survival (OS) was analyzed.

Results

There were 66 patients with high PMI and low NLR values (58%), 36 patients with a low PMI or high NLR value (32%), and 10 patients with low PMI and high NLR values (9%). The combination of the PMI and NLR did not show a significant association with the disease-free survival rate. For patients aged ≥75 years, those with both low PMI and high NLR values showed significantly shorter OS periods (log-rank: P < 0.001). In the multivariate analysis, the combination of a low PMI value and high NLR value was significantly associated with shorter survival periods (hazard ratio: 19.72; 95% confidence interval, 4.933–78.8; P < 0.001).

Conclusion

In this study, the combination of PMI and NLR was associated with prognosis in patients with early HCC and preserved liver function. The combination of the PMI and NLR may be a useful and noninvasive prognostic marker in HCC patients aged 75 years and older, as well as in younger patients.
Significant clinical outcome using pyrimethamine and clindamycin in cerebral toxoplasmosis with severe edema: a case report
Authors: Basmalah Affan Nadzar , Sugianto Paulus
Published: April 2023

Introduction and Importance:

Cerebral toxoplasmosis is a complication in HIV/AIDS patients that has recently increased in new cases due to increased HIV/AIDS incidents.

Case Presentation:

An Indonesian male, 26-year old, complained of severe headache, left hemiparesis, and tremors. A brain computed tomography scan with contrast showed a large mass, extensive edema, and a significant midline shift resembling a brain tumor. The HIV test was positive, and CD4 decreased. The patient was treated with dexamethasone, mannitol, and pyrimethamine-clindamycin as therapy. After 2 weeks of treatment, the headache, hemiparesis, and tremor were clinically improved. Two months later, a brain computed tomography scan and MRI showed a good prognosis.

Clinical Discussion:

The diagnosis of cerebral toxoplasmosis is based on a radiological examination and an HIV/AIDS test. Management of cerebral toxoplasmosis using pyrimethamine-clindamycin, while steroids are not recommended unless disproportionate cytotoxic edema is displayed and life-threatening.

Conclusion:

A combination of pyrimethamine-clindamycin, and steroids can improve the prognosis of cerebral toxoplasmosis with severe edema.
Pancreatic solid pseudopapillary neoplasm with concomitant left unilateral renal agenesis and bicornuate uterus: a case report
Authors: Bhattarai Madhur , Shrestha Ayush , Bhandari Suyog , Buha Niravkumar , Baral Rituraj , Shrivastav Shreya , Lakhey Paleswan Joshi
Published: April 2023

Introduction:

A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor of the pancreas. Concomitant SPN with urogenital anomalies is a very rare presentation.

Case Presentation:

A 16-year-old female presented with a chief complaint of abdominal pain 30 days back. Solid pseudopapillary neoplasm (SPN) of the pancreas was diagnosed with the aid of ultrasonography and contrast-enhanced computed tomography of the abdomen and pelvis. Incidentally, concomitant left unilateral renal agenesis and bicornuate uterus were also detected in radiological findings. The patient underwent spleen-preserving distal pancreatectomy, and SPN was confirmed with the histopathological report.

Discussion:

Symptomatic SPN patients present with an abdominal mass and pain or very rarely jaundice. Most of the SPNs are benign. Complete surgical excision results in more than 95% cure. SPN with concomitant urogenital anomalies is extremely rare, and their concurrent occurrence can be better attributed to Wnt signaling pathway owing to their similar pathogenic mechanism.

Conclusion:

The solid pseudopapillary tumor has an excellent prognosis if timely resected. Proper evaluation of the patient with imaging is necessary to suspect and diagnose SPN who has urogenital anomalies and vice versa.
Liposuction for Advanced Lymphedema in a Multidisciplinary Team Setting in Australia – Five-Year Follow-Up
Authors: Karlsson Tobias , Mackie Helen , Koelmeyer Louise , Heydon-White Asha , Ricketts Robyn , Toyer Kim , Boyages John , Brorson Håkan , Lam Thomas
Published: April 2023

Background:

Liposuction for International Society of Lymphology (ISL) late stage II or III limb lymphedema is an established surgical option to remove excessive adipose tissue deposition and has been performed in Australia since 2012 at the Australian Lymphoedema Education, Research and Treatment (ALERT) Program, Macquarie University.

Patients and methods:

Between May 2012 and May 2017, 72 patients with unilateral primary or secondary lymphedema of the arm or leg underwent suction-assisted lipectomy using the Brorson protocol. This prospective study presents 59 of these patients who had consented to research with a five-year follow-up.

Results:

Of the 59 patients, 54 (92%) were women, 30 (51%) had leg lymphedema and 29 (49%) had arm lymphedema. For arm patients, the median preoperative volume difference between the lymphedematous and the contralateral arm was 1061 mL, which reduced to 79 mL one year after surgery and to 22 mL five years after surgery. For leg patients, the median preoperative volume difference was 3447 mL, which reduced to 263 mL one year after surgery but increased to 669 mL five years after surgery.

Conclusions:

Suction-assisted lipectomy is a long-term option for the management of selected patients with ISL late stage II or III limb lymphedema when conservative management can offer no further improvement.
Identification of a novel HIV-1 second-generation circulating recombinant form (CRF136_0107) among men who have sex with men in China
Authors: Zhang Yun-Qi , Li Qing-Hai , Li En-Long , Wang Yi-Ru , Tang Zi-Yan , Gao Xin , Lu Ran-Ran , Liu Si-Yu , Chen Xiao-Hong , Wang Fu-Xiang , Wang Jia-Ye
Published: April 2023

Objective:

To investigate the molecular epidemiology of HIV-1 in Heilongjiang, China, and try to spot signs of new circulating recombinant form (CRF) in this region.

Design:

A molecular epidemiological study was conducted in Heilongjiang, China during 2011-2020.

Method:

Plasma samples were collected from three HIV-1 positive patients. The near full-length genome sequences (NFLGs) of a novel circulating recombinant form (CRF) were then obtained and subjected to phylogenetic analysis using Mega 7.0.26. Recombination analysis was performed by the jumping profile Hidden Markov Model (jpHMM). Finally, the origin time of this novel CRF was inferred using the Bayesian phylogenetic analysis in Beast v1.10.4.

Result:

The three NFLGs formed a distinct monophyletic cluster in the neighbor-joining (NJ) tree. Recombination analysis revealed that the recombinant genome was composed of five segments derived from CRF01_AE, subtypes B, and C, but further confirmed to be a second-generation recombinant form of CRF01_AE/CRF07_BC by a comparison of genome maps and subregion phylogenetic analysis and therefore designated as CRF136_0107. With Bayesian phylogenetic analysis, CRF136_0107 was estimated to originate around 2010-2011.

Conclusion:

A novel HIV-1 CRF01_AE/CRF07_BC second-generation CRF called CRF136_0107 was identified among men who have sex with men (MSM) in Heilongjiang, a northeast province of China.
Computed Tomography Assessment of Coronary Atherosclerosis
Authors: Varga-Szemes Akos , Maurovich-Horvat Pal , Schoepf U. Joseph , Zsarnoczay Emese , Pelberg Robert , Stone Gregg W. , Budoff Matthew J.
Published: April 2023

Arterial plaque rupture and thrombosis is the primary cause of major cardiovascular and neurovascular events. The identification of atherosclerosis, especially high-risk plaques, is therefore crucial to identify high-risk patients and to implement preventive therapies. Computed tomography angiography has the ability to visualize and characterize vascular plaques. The standard methods for plaque evaluation rely on the assessment of plaque burden, stenosis severity, the presence of positive remodeling, napkin ring sign, and spotty calcification, as well as Hounsfield Unit (HU)-based thresholding for plaque quantification; the latter with multiple shortcomings. Semiautomated threshold-based segmentation techniques with predefined HU ranges identify and quantify limited plaque characteristics, such as low attenuation, non-calcified, and calcified plaque components. Contrary to HU-based thresholds, histologically validated plaque characterization, and quantification, an emerging Artificial intelligence-based approach has the ability to differentiate specific tissue types based on a biological correlate, such as lipid-rich necrotic core and intraplaque hemorrhage that determine plaque vulnerability. In this article, we review the relevance of plaque characterization and quantification and discuss the benefits and limitations of the currently available plaque assessment and classification techniques.
Myocardial Contraction Fraction as a Simple Marker of Disease Severity in Hypertrophic Cardiomyopathy
Authors: Jiang Yuqi , Deng Wei , Dai Manyu , Li Yuguo , An Shutian , Qian Yinfeng , Bin Liu  , Yu Yongqiang , Zhao Ren , Li Xiaohu
Published: April 2023

Purpose:

Myocardial contraction fraction (MCF) of cardiac magnetic resonance (CMR) was used to evaluate myocardial function in patients with hypertrophic cardiomyopathy (HCM), which may represent a proxy marker of disease severity in HCM.

Materials and Methods:

A total of 60 HCM patients and 20 healthy controls were examined with CMR. MCF was calculated by dividing left ventricular stroke volume by left ventricular myocardial volume. The difference in MCF between late gadolinium enhancement (LGE)-positive and LGE-negative patients were compared. The differences in MCF were compared among patients with stages Ⅱ, Ⅲ, and Ⅳ of HCM. Logistic regression analysis was used to detect independent discriminants of more severe HCM. Receiver operating characteristic analysis differentiated HCM with different clinical stages.

Results:

Compared with controls (110.67±20.40%, P<0.001), values for MCF were significantly reduced in HCM (61.40±15.60%). The MCF reduction in LGE detected by CMR was more significant than in HCM patients without LGE (53.15±10.67% vs. 76.72±11.04%, P<0.001). Patients with stage IV of HCM had the lowest MCF (45.36±10.97%, P<0.05 vs. stage II and III). Lower MCF remains an independent discriminator for more severe HCM (Stage Ⅱ vs. Stage Ⅲ, odds ratio: 0.85; Stage Ⅲ vs. Stage Ⅳ, odds ratio: 0.88, all P<0.05). The optimal cutoff value for detecting more severe HCM is MCF under 66.40% (Stage Ⅱ vs. Stage Ⅲ, P<0.05) and 44.75% (Stage Ⅲ vs. Stage Ⅳ, P<0.05).

Conclusion:

MCF may be a useful and simple tool to evaluate myocardial function in patients with HCM and provide an indicator of disease severity in individuals with HCM.