bluuebunny/crossref_metadata_2025 huggingface dataset:
The Site/Group Extended Data Format and Tools
Authors: Dutheil Julien Y , Hamidi Diyar , Pajot Basile
Published: January 2024

Comparative sequence analysis permits unraveling the molecular processes underlying gene evolution. Many statistical methods generate candidate positions within genes, such as fast or slowly evolving sites, coevolving groups of residues, sites undergoing positive selection, or changes in evolutionary rates. Understanding the functional causes of these evolutionary patterns requires combining the results of these analyses and mapping them onto molecular structures, a complex task involving distinct coordinate referential systems. To ease this task, we introduce the site/group extended data format, a simple text format to store (groups of) site annotations. We developed a toolset, the SgedTools, which permits site/group extended data file manipulation, creating them from various software outputs and translating coordinates between individual sequences, alignments, and three-dimensional structures. The package also includes a Monte-Carlo procedure to generate random site samples, possibly conditioning on site-specific features. This eases the statistical testing of evolutionary hypotheses, accounting for the structural properties of the encoded molecules.
Risk factors for early recurrence after radical gastrectomy followed by adjuvant chemotherapy for stage II or III gastric cancer: a multicenter, retrospective study
Authors: Yagi Shusuke , Kumagai Koshi , Nunobe Souya , Ishizuka Naoki , Yamaguchi Toshifumi , Imai Yoshiro , Tsuda Masahiro , Haruta Shusuke , Fukunaga Hiroki , Yamada Takanobu , Goto Masahiro
Published: January 2024

Background

Radical gastrectomy followed by adjuvant chemotherapy is the standard treatment for stage II or III gastric cancer in Asian countries. Early recurrence during or after adjuvant chemotherapy is associated with poor prognosis; however, risk factors for early recurrence remain unclear.

Methods

In this multicenter, retrospective cohort study including six institutions, we evaluated the clinicopathological factors of 553 patients with gastric cancer undergoing gastrectomy followed by adjuvant chemotherapy between 2012 and 2016. Patients were divided into the following groups: early recurrence (recurrence during adjuvant chemotherapy or within 6 months after adjuvant chemotherapy completion) and non-early recurrence, which was further divided into late recurrence and no recurrence. Early-recurrence risk factors were investigated using multivariate Cox proportional hazard model. The chronological changes in the recurrence hazard were also examined for each factor.

Results

Early recurrence and late recurrence occurred in 83 (15.0%) and 73 (13.2%) patients, respectively. Based on the Cox proportional hazards model, a postoperative serum carcinoembryonic antigen level of ≥5 ng/mL (hazard ratio: 2.220, 95% confidence interval: 1.089–4.526) and a neutrophil-to-lymphocyte ratio of >1.8 (hazard ratio: 2.408, 95% confidence interval: 1.479–3.92) were identified as independent risk factors of early recurrence, but not late recurrence. The recurrence hazard ratios for neutrophil-to-lymphocyte ratio significantly decreased over time (P < 0.001) and carcinoembryonic antigen also had the same tendency (P = 0.08).

Conclusions

A carcinoembryonic antigen level of ≥5 ng/mL and a neutrophil-to-lymphocyte ratio of >1.8 are predictors of early recurrence after radical gastrectomy and adjuvant chemotherapy for stage II or III gastric cancer.
Anti-radiation effect of MRN-100: a hydro-ferrate fluid, in vivo
Authors: Ghoneum Mamdooh , Badr El-Din Nariman K , Alaa El-Dein Mai
Published: January 2024

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ-radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100’s protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5 Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation’s severe damage to important organs.
Unprecedented dengue outbreak in Taiwan following COVID-19
Authors: Chiu Nan-Chang , Chi Hsin , Weng Shun-Long , Lin Chien-Yu
Published: January 2024

Present study reports an unprecedented dengue outbreak in Taiwan post-COVID-19. Interrupted time series analysis reveals a significant surge after easing restrictions, emphasizing the roles of COVID-19 measures, especially travel restrictions, international transportation and climate change in the epidemic. Preventing and controlling dengue remain substantial challenges in the post-COVID-19 era.
Gonadal Morphology of Stillborn Hawksbill Sea Turtle (Eretmochelys imbricata) Hatchlings
Authors: Rocha Emanuel Lucas Bezerra , da Silva Lucas Gabriel Verissimo Pinheiro , Barreto Isadora Natália Rocha , Magalhães Marcela dos Santos , Dias Lucas Castanhola , Matias de Oliveira Radan Elvis , Braz Janine Karla França da Silva , de Oliveira Moacir Franco , de Moura Carlos Eduardo Bezerra
Published: January 2024

This study aimed to investigate sexual dimorphism in stillborn hawksbill sea turtles (Eretmochelys imbricata) through gonadal morphological characterizations. Macroscopic, light microscopy, and transmission electron analyses were performed for 30 gonad-mesonephros complexes. Female gonads were spindle-shaped and present a translucent whitish appearance with a grainy texture. Male gonads were approximately ovoid with a smooth opaque white surface. A primary sexual difference concerns different marrow structures, with females presenting organized cellularity featuring oocytes, lacunae, and blood vessels, while males presented a distinct organizational medulla pattern marked by testicular cords extending throughout the gonad length. Ultrastructurally, female’s stroma presented interstitial cells and an abundant cytoplasm rich in electrodense droplets and large oval germline cells, with a conspicuous and noncentral nucleus. Males, on the other hand, presented testicular cord cells containing small amounts of heterochromatin and approximately triangular apical and basal cytoplasms with an evident nucleolus characteristic of support cells. Additionally, there were cells with a large spherical nucleus compared with the cell size and a relatively scarce cytoplasm, identified as gonocytes. These findings indicate that macroscopic, microscopic, and ultrastructural evaluations are effective and reliable techniques for the sexual identification of stillborn E. imbricata hatchlings.
Increased risk of malignancy in HLA-B27-positive patients with ankylosing spondylitis requiring biologics for sustained inflammation: A long-term, single-center retrospective study
Authors: Wang Kai-Chun , Sun Yi-Syuan , Tsai Hung-Cheng , Liao Hsien-Tzung , Lai Chien-Chih , Chen Wei-Sheng , Lu Ling-Ying , Chen Ming-Han
Published: January 2024

Objectives

To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation.

Methods

Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies.

Results

During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy.

Conclusions

HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment.
Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with a modified anterolateral approach
Authors: Sakata Manabu , Hirao Makoto , Noguchi Takaaki , Okamura Gensuke , Higuchi Yusei , Tabuse Yuki , Etani Yuki , Ebina Kosuke , Tsuboi Hideki , Miyama Akira , Takahi Koichiro , Takami Kenji , Tsuji Shigeyoshi , Okada Seiji , Hashimoto Jun
Published: January 2024

Objectives

According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA.

Materials and Methods

This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups 1. conventional postoperative protocol, 2. early dorsiflexion protocol, 3. early dorsiflexion+full weight-bearing protocol. Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated.

Results

No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days.

Conclusions

Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day. Innovations in postoperative procedures for rehabilitation after TAA can be expected.
A case of systemic lupus erythematosus in a patient with Noonan syndrome with recurrent severe hypoglycaemia
Authors: Masuoka Shotaro , Tanaka Takashi , Kanaji Miwa , Furukawa Karin , Koshiba Keiko , Yamada Zento , Watanabe Eri , Kawazoe Mai , Ito Shun , Fuchigami Ayako , Nanki Toshihiro
Published: January 2024

Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto’s thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.
Risk Factors of Developing Postinfectious Irritable Bowel Syndrome in Shigellosis Patients, 5 Years After Hospitalization During the Outbreak
Authors: Soheilipour Maryam , Chahichi Atefeh , Mohajer Hamid , Ghomashi Niousha , Roohafza Hamidreza , Adibi Peyman
Published: January 2024

Background

Irritable bowel syndrome (IBS) can be triggered by bacterial dysentery. This study aimed to investigate postinfectious IBS and its risk factors after the shigellosis outbreak in hospitalized patients.

Methods

This retrospective study was conducted in 2020–2021 in referral hospitals for Shigella gastroenteritis during the 2014 shigellosis outbreak in Isfahan. The Shigella-infected group included hospitalized shigellosis patients with clinical symptoms and positive stool culture. The control group included patients matched pairwise on age and sex to the Shigella-infected group, admitted to the same hospitals in the same period with diagnoses other than shigellosis. Both groups had no history of diagnosed IBS before the outbreak. The incidence of IBS (according to Rome-III criteria) and its related factors was compared between the 2 groups 5 years after infection.

Results

Of 619 participants, 220 (35.5%) were in the Shigella-infected group. The 5-year incidence of IBS was 31.8% and 5.7% in the Shigella-infected and control groups, respectively. Multivariate analysis showed that shigellosis was significantly associated with increased risk of IBS (odds ratio [OR], 17.18 [95% confidence interval {CI}, 9.37–31.48]). Multivariate analysis indicated education level (OR, 4.15 [95% CI, 1.47–11.73]), diarrhea lasting >4 days (OR, 1.69 [95% CI, 1.17–2.44]), and abdominal cramps during the infection (OR, 0.27 [95% CI, .77–.95]) associated with postinfectious IBS (P < .05).

Conclusions

Hospitalized patients with Shigella gastroenteritis are at increased risk of IBS within 5 years after infection. Factors such as higher education level and the absence of abdominal cramps and diarrhea persisting for >5 days during hospitalization can further increase this risk.
CD155 is essential for skeletal muscle regeneration by regulating satellite cell proliferation and differentiation
Authors: Li Wenpeng , Zhang Yuan , Liu Yitian , Feng Chongyang , Duan Chujun , Zhang Zhixiang , Zhao Peng , Zhuang Ran , Ding Yong
Published: January 2024

CD155, a member of the immunoglobulin superfamily, is closely related to cell proliferation, adhesion, and migration. CD155 is overexpressed on the surface of cancer cells to promote cell proliferation and is upregulated in damaged tissues as a stress‐induced molecule. The process of skeletal muscle regeneration after injury is complex and involves injurious stimulation and subsequent satellite cell proliferation. However, the role of CD155 in this process remains unelucidated. This study aimed to explore the role of CD155 in injured skeletal muscle regeneration and to clarify its effect on satellite cell proliferation and differentiation. Here, quantitative real‐time polymerase chain reaction (RT‐qPCR) and immunofluorescence results indicated that CD155 expression in satellite cells increased after skeletal muscle injury. CD155 knockout in mice impaired the regeneration of skeletal muscle. A bone marrow transplantation mouse model was constructed and revealed that CD155 on skeletal muscle tissues, not immune cells, affected muscle regeneration. In vitro, CD155 knockdown in myoblasts inhibited their proliferation and differentiation. The transcriptomic analysis also indicated that CD155 absence can impair the biological proliferation and differentiation process of myoblasts. Our research demonstrates that CD155 directly promotes injured muscle regeneration by regulating satellite cell proliferation and differentiation, which may be a potential therapeutic molecule for skeletal muscle injury.
Lumbar Decompression With and Without Fusion for Lumbar Stenosis With Spondylolisthesis
Authors: Sastry Rahul A. , Levy Joseph F. , Chen Jia-Shu , Weil Robert J. , Oyelese Adetokunbo A. , Fridley Jared S. , Gokaslan Ziya L.
Published: January 2024

Study Design.

Markov model.

Objective.

To compare the cost-effectiveness of lumbar decompression alone (DA) with lumbar decompression with fusion (DF) for the management of adults undergoing surgery for lumbar stenosis with associated degenerative spondylolisthesis.

Summary of Background Data.

Rates of lumbar fusion have increased for all indications in the United States over the last 20 years. Recent randomized controlled trial data, however, have suggested comparable functional outcomes and lower reoperation rates for lumbar decompression and fusion as compared with DA in the treatment of lumbar stenosis with degenerative spondylolisthesis.

Materials and Methods.

A multistate Markov model was constructed from the US payer perspective of a hypothetical cohort of patients with lumbar stenosis with associated spondylolisthesis requiring surgery. Data regarding clinical improvement, costs, and reoperation were generated from contemporary randomized trial evidence, meta-analyses of recent prospective studies, and large retrospective cohorts. Base case, one-way sensitivity analysis, and probabilistic sensitivity analyses were conducted, and the results were compared with a WTP threshold of $100,000 (in 2022 USD) over a two-year time horizon. A discount rate of 3% was utilized.

Results.

The incremental cost and utility of DF relative to DA were $12,778 and 0.00529 aggregated quality adjusted life years. The corresponding incremental cost-effectiveness ratio of $2,416,281 far exceeded the willingness to pay threshold of $100,000. In sensitivity analysis, the results varied the most with respect to rate of improvement after DA, rate of improvement after lumbar decompression and fusion, and odds ratio of reoperation between the two groups. Zero percent of one-way and probabilistic sensitivity analyses achieved cost-effectiveness at the willingness-to-pay threshold.

Conclusions.

Within the context of contemporary surgical data, DF is not cost-effective compared with DA in the surgical management of lumbar stenosis with associated spondylolisthesis over a two-year time horizon.
Single-cell landscape identifies the immunophenotypes and microenvironments of HBV-positive and HBV-negative liver cancer
Authors: Zheng Qian , Sun Qi , Yao Hong , Shi Ruoyu , Wang Cheng , Ma Zhijie , Xu Haojun , Zhou Guoren , Cheng Zhangjun , Xia Hongping
Published: January 2024

Background:

HBV infection leads to HCC and affects immunotherapy. We are exploring the tumor ecosystem in HCC to help gain a deeper understanding and design more effective immunotherapy strategies for patients with HCC with or without HBV infection.

Methods:

Single-cell RNA sequencing series were integrated as a discovery cohort to interrogate the tumor microenvironment of HBV-positive (HBV+) HCC and HBV-negative (HBV−) HCC. We further dissect the intratumoral immune status of HBV+ HCC and HBV− HCC. An independent cohort, including samples treated with immune checkpoint blockade therapy, was used to validate the major finding and investigate the effect of HBV infection on response to immunotherapy.

Results:

The interrogation of tumor microenvironment indicated that regulatory T cells, exhausted CD8+ T cells, and M1-like Macrophage_MMP9 were enriched in HBV+ HCC, while mucosa-associated invariant T cells were enriched in HBV− HCC. All subclusters of T cells showed high expression of immune checkpoint genes in HBV+ HCC. Regulatory T cells enriched in HBV+ HCC also showed more robust immunosuppressive properties, which was confirmed by cross talk between immune cell subsets. The ability of antigen presentation with major histocompatibility complex-II was downregulated in HBV+ HCC and this phenomenon can be reversed by immunotherapy. Two types of HCC also present different responses to immunotherapy.

Conclusions:

There is a more immunosuppressive and exhausted tumor microenvironment in HBV+ HCC than in HBV− HCC. This in-depth immunophenotyping strategy is critical to understanding the impact of HBV and the HCC immune microenvironment and helping develop more effective treatments in patients with HCC.
Influence of the Method of Calculating the Effective Atomic Number on the Estimate of Fluorescence Yield for Metal Alloys of Biomedical Interest
Authors: Garcia Caroline V. , Souza Divanizia N. , Andrade Edson R.
Published: January 2024

This study evaluates the influence of the method used to calculate the effective atomic number (Zeff) on the estimate of secondary radiation yielded under kilovoltage x-ray beams by metal alloys with a wide range of biomedical applications. Two methods for calculating Zeff (referred to here as M1 and M2) are considered, and six metallic alloys are investigated: Ti-6Al-4 V, Co-Cr-Mo, Ni-Cr-Ti, Ni-Cr, Co-Cr-Mo-W, and Ag3Sn-Hg (amalgam). The results indicate significant differences in the estimates of fluorescence yield depending on the method used to estimate Zeff for each metallic alloy. Both the choice of the calculation method for Zeff and the energy ranges of the incident radiation are essential factors affecting the behavior of alloys in terms of fluorescence production. Our results may guide the selection of the best material for a biomedical application. The metallic alloys simulated here show equivalences and discrepancies that depend on the method used to estimate Zeff and the energy range of the incident photons. This finding allows for the creation of combinations of alloys and methods for calculating Zeff and the photon energy to maximize safety and minimize cost.
The Soluble Urokinase Plasminogen Activator Receptor as a Severity Biomarker in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome
Authors: Louka Magdalini , Tatsi Elizabeth Barbara , Vassiliu Sofia , Theoharis George , Straka Kalliopi , Filippatos Filippos , Dourdouna Maria Myrto , Siahanidou Tania , Syriopoulou Vasiliki , Michos Athanasios
Published: January 2024

Background:

Elevated soluble urokinase plasminogen activator receptor (suPAR) has been associated with a poor prognosis in serious infections. The aim of this study was to evaluate the clinical value of suPAR in children with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C).

Methods:

Serum suPAR was measured using the suPARnostic AUTO Flex enzyme-linked immunosorbent assay in hospitalized children with COVID-19, MIS-C, bacterial pneumonia, and healthy controls.

Results:

A total of 211 children with a mean (±SD) age of 6.9 ± 4.96 years were tested; with COVID-19: 59 (28%), MIS-C: 36 (17%), pneumonia: 78 (37%) and healthy controls: 38 (18%). In the acute phase, the levels of suPAR (mean ± SD) were: MIS-C: 8.11 ± 2.80 ng/mL, COVID-19: 4.91 ± 1.90 ng/mL, pneumonia: 4.25 ± 1.44 ng/mL and controls: 2.09 ± 0.47 ng/mL (P < 0.001). Children with acute COVID-19 and a severe or moderate clinical presentation had higher values than those with mild symptoms: 5.79 ± 1.58 versus 5.40 ± 1.94 versus 3.19 ± 0.73 ng/mL, respectively (P < 0.001). In the MIS-C group, children hospitalized in the intensive care unit and in need of mechanical ventilation had higher suPAR than those who were not admitted to an intensive care unit: 9.32 ± 3.06 versus 7.13 ± 2.19 ng/mL, respectively (P = 0.023). In children with COVID-19 or MIS-C, a correlation was detected between suPAR values and length of hospitalization (r

s
= 0.418, P < 0.001).

Conclusions:

The findings suggest that suPAR may be a valuable biomarker of disease severity in children with COVID-19 or MIS-C. This could facilitate the identification of children in need of intensive anti-inflammatory treatment, as it has been shown in adults with severe COVID-19.
Risk factors of more severe hypotension after spinal anesthesia for cesarean section
Authors: Li Yi-Shiuan , Lin Shih-Pin , Horng Huann-Cheng , Tsai Shiang-Wei , Chang Wen-Kuei
Published: January 2024

Background:

The aim of this study was to examine the risk factors associated with the use of vasopressors to prevent hypotension that occurs after spinal anesthesia during cesarean section. Although the prophylactic use of vasopressors is already suggested as routine care in many parts of the world, the occurrence of spinal anesthesia-induced hypotension (SAIH) is still common in parturients.

Methods:

This retrospective study included parturients receiving elective cesarean deliveries under spinal anesthesia from April 2016 to March 2020. Risk factors related to ephedrine dosage were analyzed using a hurdle model, and risk factors related to SAIH were further analyzed with logistic regression.

Results:

Five risk factors, namely maternal body mass index (BMI, p < 0.001), baseline systolic blood pressure (SBP, p < 0.001), baseline heart rate (HR, p = 0.047), multiparity (p = 0.003), and large fetal weight (p = 0.005) were significantly associated with the requirement for ephedrine. Furthermore, a higher ephedrine dosage was significantly associated with maternal BMI (p < 0.001), baseline SBP (p < 0.001), baseline HR (p < 0.001), multiparity (p = 0.027), large fetal weight (p = 0.030), maternal age (p = 0.009), and twin pregnancies (p < 0.001). Logistic regression analysis also showed that the same five risk factors—maternal BMI (p = 0.030), baseline SBP (p < 0.001), baseline HR (p < 0.001), multiparity (p < 0.001), and large fetal weight (p < 0.001)—were significantly associated with SAIH, even in cases where vasopressors were administered.

Conclusion:

These findings can be useful for clinicians when deciding the dose of prophylactic ephedrine or phenylephrine to prevent SAIH.
Predictive value of local control by 4’-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma
Authors: Ouchi Yohei , Kishino Takehito , Miyashita Takenori , Mori Terushige , Mitamura Katsuya , Norikane Takashi , Yamamoto Yuka , Hoshikawa Hiroshi
Published: January 2024

Purpose

We investigated the potential of baseline 4′-[methyl-11C]-thiothymidine ([11C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC).

Methods

A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [11C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction.

Results

The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 (P < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively.

Conclusion

Baseline [11C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.
Transfusion strategies for neonates: current perspectives
Authors: Shafique Muhammed A. , Abbas Syeda Q. , Habiba Ume , Mughal Aira , Fadlalla Ahmad Tagwa Kalool , Munir Chaudhary Anfal
Published: January 2024

Background:

Blood transfusion intervention has been proven to be a crucial therapeutic aid for preterm infants with serious morbidities such as sepsis, intraventricular hemorrhage, and cardiopulmonary insufficiencies. However, blood transfusion practices have also been shown to cause significant adverse outcomes, which may negate the therapeutic effect of the intervention. To address the varying policies regarding the administration of blood products, healthcare professionals have adopted a consensus-based approach. The absence of a standard protocol has resulted in conflicting outcomes in previous clinical studies.

Objective:

This study aimed to evaluate the effectiveness of blood transfusion practices in preterm infants by analyzing past clinical research and identifying the current trends that have emerged as a result of recent trials.

Results:

Recent trials have demonstrated comparable trends in mortality rates and other primary outcomes, including retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, and brain injury, following transfusion of blood products in both groups. Nevertheless, employing restrictive thresholds rather than adopting a liberal approach can reduce these outcomes.

Conclusion:

The current literature does not provide clear support for either technique as opposing and contradictory results are evident. However, there is a slight inclination toward the restrictive transfusion threshold due to recent trials, which warrants further in-depth investigation into this issue.
Point prevalence and clinical profile of patients with delirium admitted in internal medicine department at tertiary care centre in eastern Nepal: a descriptive cross-sectional study
Authors: Yogi Tek Nath , Puri Sujan , Shah Bhupendra , Nepal Suraj , Mishra Akshat
Published: January 2024

Introduction:

Delirium, marked by acute disturbances in consciousness and cognition, remains underdiagnosed despite its significant impact on morbidity and mortality. This study investigates the point prevalence and clinical profile of delirium in patients at an eastern Nepal tertiary care centre.

Methods:

A 1-month descriptive cross-sectional study involved 152 Internal Medicine Department patients at BPKIHS, Dharan. Data, collected through face-to-face interviews and the Confusion Assessment Method (CAM), analyzed demographic details, clinical history, and laboratory findings. Ethical clearance and informed consent were obtained.

Results:

Among 152 participants, 13.2% exhibited delirium, with notable risk factors identified. Elderly patients (≥65 years) and those with nasogastric tubes faced higher risks. Significant associations were found with cardiovascular diseases (P=0.002), central nervous system diseases (P=0.015), and alcoholism (P=0.003). Laboratory findings revealed correlations with elevated creatinine, hyperuremia, and abnormal aspartate aminotransferase levels. The study emphasizes key contributors to delirium, providing valuable insights for clinicians in identifying, preventing, and managing delirium in a hospital setting.

Conclusions:

This study provides critical insights into delirium prevalence and profiles in Eastern Nepal. Identified risk factors underscore the importance of routine screenings and targeted interventions for at-risk populations. Study limitations, including sample size and single-centre focus, call for further research to validate findings and enhance our understanding of delirium’s management across diverse healthcare settings. Overall, the study informs clinical practices and prompts broader exploration of delirium in healthcare contexts.
Analysis of Clinical Characteristics and Influencing Factors of Early Neurological Deterioration in Patients With Mild Stroke by Intravenous Alteplase Therapy
Authors: Mao Xin-Lei , He Si-Si , Lin Cai-Dan , Huang Xiang-Dong , Sun Jun
Published: January 2024

Objectives:

Thrombolysis treatment for patients with mild stroke is controversial. The aim of our study was to investigate the clinical characteristics and influencing factors of early neurological deterioration (END) in this group of patients.

Methods:

A retrospective analysis was performed on ischemic stroke patients with intravenous thrombolysis (IVT) in Wenzhou Central Hospital. Subgroup analyses were performed for the mild stroke group and nonmild stroke group, END group, and non–early neurological deterioration group in mild stroke patients, respectively.

Results:

A total of 498 patients were included in this study. Compared with the control group, the mild stroke group was younger age, less atrial fibrillation, previous history of stroke and less use of antithrombotic drugs, more dyslipidemia, smoking, and drinking. Small artery occlusion type was more common in mild stroke, cardioembolism and stroke of undetermined etiology type were less. In the mild stroke group, the symptomatic intracerebral hemorrhage (sICH) rate was 2.54%, and the END rate was 16.1%. Predictors of END included systolic blood pressure, blood glucose, cardioembolism subtype, sICH, and large vessel occlusion. In END patients, the sICH rate was 10.53%, and 84.21% of cases started to worsen within 12 hours after IVT. There was no statistically significant difference in the time to exacerbation among different subtypes.

Conclusions:

The occurrence of mild stroke in young patients was largely related to unhealthy lifestyles. The incidence of END in mild stroke IVT patients was low, with most occurring within 12 hours of IVT. There were many risk factors for END: large vessel occlusion and hyperglycemia were independent risk factors for END after IVT. sICH was an important but rare risk factor for END.
The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implication
Authors: Elkady Noha , Allam Dina M.
Published: January 2024

Colorectal cancer (CRC) is a leading cause of death worldwide. Despite the advances in surgical and therapeutic management, tumor metastases and poor prognosis are still major problems. Tumor budding is a relevant prognostic factor in CRC, and it can predict tumor metastasis. Galectin3 is responsible for the development and progression of many cancers through the regulation of cell-cell/cell-matrix interactions and tumor cell invasion. Tubulin is a microtubule protein, and maspin is a serine protease inhibitor; both induce tumor cell invasion through the stimulation of epithelial-mesenchymal transition. This study aims to evaluate the relationship between the expression of galecin3, tubulinβ, and maspin in CRC and clinicopathological features, including tumor budding, their prognostic roles, and clinical implications using immunohistochemistry. Galectin3, tubulinβ, and maspin were detected in tumor cells in 95%, 65%, and 87.5% of cases and in stromal cells in 28.8%, 40%, and 0% of cases. High expression of galectin3 and tubulinβ expression either in tumor cells or stroma was significantly associated with aggressive tumor features such as lymph node metastasis, lymphovascular invasion, tumor budding, and advanced tumor stage. The nucleocytoplasmic expression of maspin in tumor cells showed a significant association with deeper tumor invasion, lymph node metastasis, tumor budding, and advanced tumor stage. Significant associations were found between high galectin3 tumor cell expression and nucleocytoplasmic maspin and shorter survival. High expression of galectin3, tubulinβ, and nucleocytoplasmic maspin were significantly associated with aggressive tumor features such as tumor invasion, metastasis, high tumor budding, and short survival in CRC. They could be used as biomarkers for tumor budding and tumor aggressiveness in CRC and may be considered for future target therapy.
Altered functional connectivity between the default mode network in primary angle-closure glaucoma patients
Authors: Tang Qiu-Yu , Huang Bing-Lin , Huang Xin
Published: January 2024

Previous studies have recognized glaucoma as a neurodegenerative disease that causes extensive brain damage and is closely associated with cognitive function. In this study, we employed functional MRI to examine the intrinsic functional connectivity patterns of the default mode network (DMN) in patients diagnosed with primary angle-closure glaucoma (PACG), exploring its association with cognitive dysfunction. A total of 34 patients diagnosed with PACG and 34 healthy controls (HC), who were matched in terms of sex, age, and education, were included in the control group. The posterior cingulate cortex (PCC) was selected as the region of interest to examine functional connectivity alterations. Compared with the HC group, functional connectivity was attenuated in left anterior cingulum cortex and left paracentral lobule between with PCC in the PACG group, the results are statistically significant. Our study revealed that patients with PACG exhibit weakened functional connectivity within the DMN. This finding suggests the presence of a neurological mechanism that is associated with both visual dysfunction and cognitive impairments in PACG patients. Furthermore, our study provides neuroimaging evidence that can aid in the exploration of spontaneous neurological alterations and facilitate a deeper investigation of alterations in the visual conduction pathways of PACG patients.
Valid publication of names of two domains and seven kingdoms of prokaryotes
Authors: Göker Markus , Oren Aharon
Published: January 2024

The International Code of Nomenclature of Prokaryotes (ICNP) now includes the categories domain and kingdom. For the purpose of the valid publication of their names under the ICNP, we consider here the two known domains, ‘Bacteria’ and ‘Archaea’, as well as a number of taxa suitable for the rank of kingdom, based on previous phylogenetic and taxonomic studies. It is proposed to subdivide the domain Bacteria into the kingdoms Bacillati, Fusobacteriati, Pseudomonadati and Thermotogati. This arrangement reflects contemporary phylogenetic hypotheses as well as previous taxonomic proposals based on cell wall structure, including ‘diderms’ vs. ‘monoderms’, Gracilicutes vs.

Firmicutes

, ‘Negibacteria’ vs. ‘Unibacteria’, ‘Hydrobacteria’ vs. ‘Terrabacteria’, and ‘Hydrobacterida’ vs. ‘Terrabacterida’. The domain Archaea is proposed to include the kingdoms Methanobacteriati, Nanobdellati and Thermoproteati, reflecting the previous division into ‘

Euryarchaeota

’, ‘DPANN superphylum’ and ‘TACK superphylum’.
Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits
Authors: Curylova Lucie , Staniczkova Zambo Iva , Neradil Jakub , Kyr Michal , Jurackova Nicola , Pavlova Sarka , Polaskova Kristyna , Mudry Peter , Sterba Jaroslav , Veselska Renata , Skoda Jan
Published: January 2024

Pediatric sarcomas are bone and soft tissue tumors that often exhibit high metastatic potential and refractory stem-like phenotypes, resulting in poor outcomes. Aggressive sarcomas frequently harbor a disrupted p53 pathway. However, whether sarcoma stemness is associated with abrogated p53 function and might be attenuated via p53 reactivation remains unclear. Here, we show that highly tumorigenic stem-like sarcoma cells exhibit dysregulated p53, making them vulnerable to drugs that restore wild-type p53 activity. Immunohistochemistry of mouse xenografts and human tumor tissues revealed that p53 dysregulations together with enhanced expression of the stemness-related transcription factors SOX2 or KLF4 are crucial features in pediatric osteosarcoma, rhabdomyosarcoma, and Ewing’s sarcoma development. p53 dysregulation appears to be an important step for sarcoma cells to acquire a fully stem-like phenotype, and p53-positive pediatric sarcomas exhibit a high frequency of early metastasis. Importantly, p53 signaling reactivation via MDM2/MDMX inhibition selectively induces apoptosis in aggressive stem-like Ewing’s sarcoma cells while sparing healthy fibroblasts. Collectively, our results suggest that restoration of canonical p53 activity provides a promising strategy for improving the treatment of pediatric sarcomas with unfavorable stem-like traits.

HIGHLIGHTS

SOX2 and KLF4 are crucial factors in pediatric sarcoma tumorigenesis

Dysregulated p53 pathway predisposes sarcoma cells to acquire stem-like features

p53 positivity is associated with early metastasis in pediatric sarcoma patients

Restoring wild-type p53 signaling selectively kills stem-like Ewing’s sarcoma cells
Inhibition of Multiple Staphylococcal Growth States by a Small Molecule that Disrupts Membrane Fluidity and Voltage
Authors: Dombach Jamie L. , Christensen Grace L. , Allgood Samual C. , Quintana Joaquin LJ , Detweiler Corrella S.
Published: January 2024

New molecular approaches to disrupting bacterial infections are needed. The bacterial cell membrane is an essential structure with diverse potential lipid and protein targets for antimicrobials. While rapid lysis of the bacterial cell membrane kills bacteria, lytic compounds are generally toxic to whole animals. In contrast, compounds that subtly damage the bacterial cell membrane could disable a microbe, facilitating pathogen clearance by the immune system with limited compound toxicity. A previously described small molecule, D66, terminatesSalmonella entericaserotype Typhimurium (S.Typhimurium) infection of macrophages and reduces tissue colonization in mice. The compound dissipates bacterial inner membrane voltage without rapid cell lysis under broth conditions that permeabilize the outer membrane or disable efflux pumps. In standard media, the cell envelope protects Gram-negative bacteria from D66. We evaluated the activity of D66 in Gram-positive bacteria because their distinct envelope structure, specifically the absence of an outer membrane, could facilitate mechanism of action studies. We observed that D66 inhibited Gram-positive bacterial cell growth, rapidly increasedStaphylococcus aureusmembrane fluidity, and disrupted membrane voltage while barrier function remained intact. The compound also prevented planktonic staphylococcus from forming biofilms and disturbed three-dimensional structure in one-day-old biofilms. D66 furthermore reduced the survival of staphylococcal persister cells and of intracellularS. aureus. These data indicate that staphylococcal cells in multiple growth states germane to infection are susceptible to changes in lipid packing and membrane conductivity. Thus, agents that subtly damage bacterial cell membranes could have utility in preventing or treating disease.

Importance

An underutilized potential antibacterial target is the cell membrane, which supports or associates with approximately half of bacterial proteins and has a phospholipid makeup distinct from mammalian cell membranes. Previously, an experimental small molecule, D66, was shown to subtly damage Gram-negative bacterial cell membranes and to disrupt infection of mammalian cells. Here we show that D66 increases the fluidity of Gram-positive bacterial cell membranes, dissipates membrane voltage, and inhibits the human pathogenStaphylococcus aureusin several infection-relevant growth states. Thus, compounds that cause membrane damage without lysing cells could be useful for mitigating infections caused byS. aureus.
Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients
Authors: Gondal Mahnoor N. , Cieslik Marcin , Chinnaiyan Arul M.
Published: January 2024

Immune checkpoint blockade (ICB) therapies have emerged as a promising avenue for the treatment of various cancers. Despite their success, the efficacy of these treatments is variable across patients and cancer types. Numerous single-cell RNA-sequencing (scRNA-seq) studies have been conducted to unravel cell-specific responses to ICB treatment. However, these studies are limited in their sample sizes and require advanced coding skills for exploration. Here, we have compiled eight scRNA-seq datasets from nine cancer types, encompassing 174 patients, and 90,270 cancer cells. This compilation forms a unique resource tailored for investigating how cancer cells respond to ICB treatment across cancer types. We meticulously curated, quality-checked, pre-processed, and analyzed the data, ensuring easy access for researchers. Moreover, we designed a user-friendly interface for seamless exploration. By sharing the code and data for creating these interfaces, we aim to assist fellow researchers. These resources offer valuable support to those interested in leveraging and exploring single-cell datasets across diverse cancer types, facilitating a comprehensive understanding of ICB responses.
Testing for reciprocal trait influence in plant-frugivore interactions using generalized joint attribute modeling
Authors: Yohe Laurel R. , Miller Leith B. , Kaliszewska Zofia A. , Whitehead Susan R. , Santana Sharlene E. , Dávalos Liliana M.
Published: January 2024

Under an adaptive hypothesis, the reciprocal influence between mutualistic plants and frugivores is expected to result in dispersal syndromes comprising both frugivore and plant traits that structure fruit consumption. Tests of this adaptive hypothesis, however, focus on traits of either fruits or frugivores but not both and often ignore within-species variation. To overcome these limitations, we analyze traits for the mutualistic ecological network comprisingCarolliabats that feed on and dispersePiperseeds. For these analyses, we use generalized joint attribute modeling (GJAM), a Bayesian modeling approach that simultaneously accounts for multiple sources of variance across trait types. In support of the adaptive hypothesis and indicating niche partitioning amongCarolliabats, we find differential consumption of a suite ofPiperspecies influenced by bat traits such as body size; however,Pipermorphological traits had no effect on bat consumption. Slow evolutionary rates, dispersal by other vertebrates, and unexamined fruit traits, such asPiperchemical bouquets, may explain the lack of association between batPiperconsumption and fruit morphological traits. We have identified a potential asymmetric influence of frugivore traits on plant-frugivore interactions, providing a template for future trait analyses of plant-animal networks.