bluuebunny/crossref_metadata_2025 huggingface dataset:
Another de novo mutation in the SOD1 gene: the first Turkish patient with SOD1-His47Arg, a case report
Authors: Bayraktar Elif , Çiftçi Vildan , Uysal Hilmi , Başak A. Nazlı
Published: August 2023

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease of motor neurons. Most ALS cases are considered sporadic due to the presence of a combination of environmental and complex genetic risk factors, while approximately 10% of cases have a family history. Pathogenic variants in the SOD1 gene are the second most frequent causative factor of genetics-based ALS worldwide, after C9ORF72 hexanucleotide repeat expansion. The De novo occurrence of pathogenic mutations in ALS-associated genes and its effect on disease progression have been studied previously, especially in the FUS gene. Recent studies have shown that a very small portion of SOD1 cases occurred de novo. Here, we present the first de novo case of the SOD1 His47Arg mutation in a young female patient with mild symptoms and, currently, a slow progression for 7 years.
Construction of a genetic map and QTL mapping of seed size traits in soybean
Authors: Jiang Aohua , Liu Jiaqi , Gao Weiran , Ma Ronghan , Tan Pingting , Liu Fang , Zhang Jian
Published: August 2023

Soybean seed size and seed shape traits are closely related to plant yield and appearance quality. In this study, 186 individual plants of the F2 generation derived from crosses between Changjiang Chun 2 and JiYu 166 were selected as the mapping population to construct a molecular genetic linkage map, and the phenotypic data of hundred-grain weight, seed length, seed width, and seed length-to-width ratio of soybean under three generations of F2 single plants and F2:3 and F2:4 lines were combined to detect the QTL (quantitative trait loci) for the corresponding traits by ICIM mapping. A soybean genetic map containing 455 markers with an average distance of 6.15 cM and a total length of 2799.2 cM was obtained. Forty-nine QTLs related to the hundred-grain weight, seed length, seed width, and seed length-to-width ratio of soybean were obtained under three environmental conditions. A total of 10 QTLs were detected in more than two environments with a phenotypic variation of over 10%. Twelve QTL clusters were identified on chromosomes 1, 2, 5, 6, 8, 13, 18, and 19, with the majority of the overlapping intervals for hundred-grain weight and seed width. These results will lay the theoretical and technical foundation for molecularly assisted breeding in soybean seed weight and seed shape. Eighteen candidate genes that may be involved in the regulation of soybean seed size were screened by gene functional annotation and GO enrichment analysis.
A GATA3 gene mutation that causes incorrect splicing and HDR syndrome: a case study and literature review
Authors: Tao Yilun , Yang Lin , Han Dong , Zhao Chen , Song Wenxia , Wang Haiwei , Li Xiaoze , Wang Lihong
Published: August 2023

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an infrequent autosomal dominant genetic disorder caused by haploinsufficiency of the GATA binding protein 3 (GATA3) gene. In this report, we present a case study of a 6-year-old female patient manifesting seizures, tetany, hypoparathyroidism, and sensorineural hearing loss. A heterozygous variant, c.1050 + 2T>C, in the GATA3 gene was discovered by genetic testing. Moreover, a minigene splicing experiment revealed that the aforementioned variation causes incorrect splicing and premature cessation of protein synthesis. The clinical profile of the patient closely resembles the well-known phenomenology of HDR syndrome, supporting the association between the condition and the GATA3 variant. The challenges in early diagnosis highlight the importance of employing next-generation sequencing for timely detection of rare diseases. Additionally, this research contributes to a deeper understanding of the genotype-phenotype correlations in HDR syndrome, underscoring the critical need for improved diagnostic and therapeutic strategies.
Dynamics of IgG antibody response against Plasmodium antigens among Nigerian infants and young children
Authors: Leonard Colleen M. , Uhomoibhi Perpetua , Abubakar Ado , Ogunniyi Abiodun , Mba Nwando , Greby Stacie M. , Okoye McPaul I. , Iriemenam Nnaemeka C. , Ihekweazu Chikwe , Steinhardt Laura , Rogier Eric ,   NMS4 Technical Working Group
Published: August 2023

Background

Plasmodium falciparum malaria is a leading cause of child mortality in Nigeria. Neonates are born with maternal antibodies from placental transfer which may protect against malaria infection in the first months of life. The IgG dynamics of the transition from passively transferred antimalarial antibodies to actively acquired IgG from natural exposure have not been well elucidated.

Methods

Blood samples collected during a 2018 Nigeria nationwide HIV/AIDS household survey were available for 9,443 children under 5 years of age, with a subset of infants under 2 months of age having maternal samples available (n=41). Samples were assayed for the P. falciparum HRP2 antigen and anti-malarial IgG antibodies. LOESS regression examined the dynamics in IgG response in the first 5 years of life. Correlation with maternal IgG levels was assessed for mother/child pairs.

Results

Consistent decreases were observed in median IgG levels against all Plasmodium spp. antigen targets for the first months of life. At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. Seropositivity showed a similar decline with the lowest seropositivity against AMA1 and PfMSP1 at 10-12 months, though remaining above 50% during the first 2 years of life in higher transmission areas. No protective association was observed between IgG positivity and P. falciparum infection in infants. Maternal antibody levels showed a strong positive correlation with infant antibody levels for all P. falciparum antigens from birth to 2 months of age, but this correlation was lost by 6 months of age.

Discussion

Maternally transferred anti-malarial IgG antibodies rapidly decline during the first 6 months of life, with variations among specific antigens and malaria transmission intensity. From 3-23 months of age, there was a wide range in IgG levels for the blood-stage antigens indicating high individual variation in antibody production as children are infected with malaria. Non-falciparum species-specific antigens showed similar patterns in waning immunity and correlation with paired mother’s IgG levels compared to P. falciparum antigens.
The m6A-related gene signature stratifies poor prognosis patients and characterizes immunosuppressive microenvironment in hepatocellular carcinoma
Authors: Ma Ensi , Li Jianhua , Shen Conghuan , Gu Yange , Zhang Xinju , Li Li , Zhao Jing , Wang Zhengxin
Published: August 2023

Background

N6-methyladenosine (m6A) is the most abundant epitranscriptomic modification of RNA, which can affect RNA metabolism and protein translation. The m6A modification plays a critical role in cancer development, including hepatocellular carcinoma (HCC). Despite several m6A-related signatures in HCC, most of them lack the necessary validation and the reliability is still elusive.

Methods

Differentially expressed genes (DEGs) in the Cancer Genome Atlas were comprehensively analyzed to identify m6A signature associated with HCC prognosis. Gene set enrichment analysis, tumor mutation burden (TMB), immune infiltration, and therapeutic response were evaluated. Importantly, mass spectrometry proteomics and multiplex immunofluorescence assays were performed for validation.

Results

The m6A-related protein-coding gene signature was established, which can divide HCC into high-/low-risk subgroups with markedly different overall survival (OS) and clinical stages. Furthermore, we validated its reliability and robustness in our 101 independent HCC specimens using proteomic detection and confirmed that our signature readily identified high-risk HCC patients with 3-year survival rates of 44.1% vs. 71.8% in the low-risk group. Functional analysis indicated that the high-risk group might stimulate the cell cycle and activate oncogenic pathways such as MAPK, mTOR, and VEGF, whereas the low-risk group mainly regulated amino acid, fatty acid, and drug metabolism. Additionally, the high-risk group had more TMB, upregulated immune checkpoint molecule expression, including PD-1, CTLA4, TIM3, and LAG3, and preferentially formed an immunosuppressive microenvironment. Accordingly, potential therapeutic responses showed that high-risk patients were potentially sensitive to inhibitors targeting the cell cycle and MAPK signaling, with patients possibly benefiting from immunotherapy. Moreover, multiplex immunofluorescence assays indicated that high-risk HCC samples displayed distinct immunosuppressive features, with abundant M2-polarized macrophages and T-regulatory cell infiltration.

Conclusion

The m6A signature had a prominent capacity to evaluate OS and characterize the tumor immune microenvironment of HCC, which may serve as a useful approach for risk stratification management and provide a valuable clue to choosing rational therapeutic strategies.
CXCR5 and TIM-3 expressions define distinct exhausted T cell subsets in experimental cutaneous infection with Leishmania mexicana
Authors: Diupotex Mariana , Zamora-Chimal Jaime , Gajón Julián A. , Bonifaz Laura C. , Becker Ingeborg
Published: August 2023

T-cell exhaustion is a key stage in chronic infections since it limits immunopathology, but also hinders the elimination of pathogens. Exhausted T (Tex) cells encompass dynamic subsets, including progenitor cells that sustain long-term immunity through their memory/stem like properties, and terminally-differentiated cells, resembling the so-called Tex cells. The presence of Tex cells in chronic leishmaniasis has been reported in humans and murine models, yet their heterogeneity remains unexplored. Using flow cytometry, we identified Tex cells subtypes based on PD-1, CXCR5 and TIM-3 expressions in draining lymph nodes (dLNs) and lesion sites of C57BL/6 mice infected with L. mexicana at 30-, 60- and 90-days post-infection. We showed that infected mice developed a chronic infection characterized by non-healing lesions with a high parasite load and impaired Th1/Th2 cytokine production. Throughout the infection, PD-1+ cells were observed in dLNs, in addition to an enhanced expression of PD-1 in both CD4+ and CD8+ T lymphocytes. We demonstrated that CD4+ and CD8+ T cells were subdivided into PD-1+CXCR5+TIM-3- (CXCR5+), PD-1+CXCR5+TIM-3+ (CXCR5+TIM-3+), and PD-1+CXCR5-TIM-3+ (TIM-3+) subsets. CXCR5+ Tex cells were detected in dLNs during the whole course of the infection, whereas TIM-3+ cells were predominantly localized in the infection sites at day 90. CXCR5+TIM-3+ cells only increased at 30 and 60 days of infection in dLNs, whereas no increase was observed in the lesions. Phenotypic analysis revealed that CXCR5+ cells expressed significantly higher levels of CCR7 and lower levels of CX3CR1, PD-1, TIM-3, and CD39 compared to the TIM-3+ subset. CXCR5+TIM-3+ cells expressed the highest levels of all exhaustion-associated markers and of CX3CR1. In agreement with a less exhausted phenotype, the frequency of proliferating Ki-67 and IFN-γ expressing cells was significantly higher in the CXCR5+ subset within both CD4+ and CD8+ T cells compared to their respective TIM-3+ subsets, whereas CD8+CXCR5+TIM-3+ and CD8+TIM-3+ subsets showed an enhanced frequency of degranulating CD107a+ cells. In summary, we identified a novel, less-differentiated CXCR5+ Tex subset in experimental cutaneous leishmaniasis caused by L. mexicana. Targeting these cells through immune checkpoint inhibitors such as anti-PD-1 or anti PD-L1 might improve the current treatment for patients with the chronic forms of leishmaniasis.
Population connectivity and dynamics in early-life stages of Atlantic fish communities
Authors: Pereira Gabellini Aurelia , Mariani Patrizio , Christensen Asbjørn
Published: August 2023

Introduction

Many hypotheses have been suggested to explain recruitment variability in fish populations. These can generally be divided into three groups, either related to: larval food limitation, predation, or transport. Transport mechanisms are central for reproduction in pelagic species and three physical processes, concentration, enrichment, and retention are commonly referred as the fundamental “ocean triads” sustaining larval survival and thus success of reproductive effort. The aim of this study is to investigate linkages between primary production and transport processes of eggs and larvae for the most important commercial fish species in the Atlantic Ocean.

Methods

We simulated eggs and larvae dispersion using an individualbased model and integrating information on the fish ecology of the major fish stocks. Our work included a review on spawning ground locations, spawning time, eggs and larvae duration. Simulations were performed over a 10-year time period for 113 stocks (17 species) in order to assess variability in dispersion and common trends and factors affecting transport.

Results

The level of primary production from initial to final position, i.e. from spawning to larval settlement, increased for some stocks (n=31), for others it declined (n=64), and for a smaller group (n=18) there was no substantial changes in level of primary production.

Discussion

This result implies that larval transport will not necessarily introduce larvae into areas of enhanced food availability expressed by the primary production at the site. These findings thus suggest marked differences in how physical and biological processes interact in the early life of major fish groups in the Atlantic Ocean. The results provide a further insight into fish larval drift and the potential role of primary production in emergence of spawning strategies.
Foraging movements of humpback whales relate to the lateral and vertical distribution of capelin in the Barents Sea
Authors: Vogel Emma F. , Skalmerud Stine , Biuw Martin , Blanchet Marie-Anne , Kleivane Lars , Skaret Georg , Øien Nils , Rikardsen Audun
Published: August 2023

Understanding how individual animals modulate their behaviour and movement patterns in response to environmental variability plays a central role in behavioural ecology. Marine mammal tracking studies typically use physical environmental characteristics that vary, and/or proxies of prey distribution, to explain predator movements. Studies linking predator movements and the actual distributions of prey are rare. Here we analysed satellite tag data from ten humpback whales in the Barents Sea (north-east Atlantic) to examine how their spatial movement and dive patterns are influenced by the geographic and vertical distribution of capelin, which is a key prey species for humpback whales. We used capelin density estimates based on direct observations from a trawl-acoustic survey and sun elevation to explore the drivers of changes in movement patterns. We found that the humpback whales’ exhibited characteristic area restricted search movement where capelin density was the highest. While horizontal movements showed both positive and negative individual relationships with sun elevation, humpback whale dive depth was positively correlated with diurnal variations in the vertical distribution of capelin. This suggests that in addition to whales foraging in regions of high capelin density, they also target the densest shoals of capelin at a range of depths, throughout the day and night. Overall, our findings suggest that regions of high capelin density are important foraging grounds for humpback whales, highlighting the central role capelin plays in the Barents Sea marine ecosystem.
Is acupuncture safe in the ICU? A systematic review and meta-analysis
Authors: Ben-Arie Eyal , Lottering Bernice Jeanne , Chen Fang-Pey , Ho Wen-Chao , Lee Yu-Chen , Inprasit Chanya , Kao Pei-Yu
Published: August 2023

Background and purpose

The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured.

Methods

In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality.

Results

A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference −1.45 [−11.94, −10.97], P = 0.00001, I2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I2 = 0%).

Conclusion

There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142131, identifier: CRD42020142131.
Association of serum lipids with inflammatory bowel disease: a systematic review and meta-analysis
Authors: Chen Hongxin , Li Weiyang , Hu Jingyi , Xu Feng , Lu Yizhou , Zhu Lei , Shen Hong
Published: August 2023

Background

Serum lipid levels seem to be abnormal in Inflammatory bowel disease (IBD). However, the specific manifestation of abnormal serum lipid levels in IBD are heterogeneous among studies and have not been sufficiently determined yet.

Methods

PubMed, EMBASE, and Cochrane Library databases were searched. Serum lipid levels were compared between IBD patients and Health individuals, Crohn’s (CD) and ulcerative colitis (UC), active and inactive, mild and non-mild patients, respectively. Meta-analyses were performed by using a random-effect model. Weight mean difference (WMD) with 95% confidence intervals (CIs) were calculated.

Results

Overall, 53 studies were included. Compared with healthy controls, IBD patients had significantly lower TC (WMD = −0.506, 95%CI = −0.674 to −0.338, p < 0.001), HDL-c (WMD = −0.122, 95%CI = −0.205 to −0.039, p = 0.004), and LDL-c (WMD = −0.371, 95%CI = −0.547 to −0.194, p < 0.001) levels. CD groups had a significantly lower TC (WMD = −0.349, 95%CI = −0.528 to −0.170, p < 0.0001) level as compared to UC groups. Active IBD and non-mild UC groups had significantly lower TC (WMD = −0.454, 95%CI = −0.722 to −0.187, p = 0.001) (WMD =0.462, 95%CI = 0.176 to 0.748, p = 0.002) and LDL-c (WMD = −0.225, 95%CI = −0.445 to −0.005, p = 0.045) (WMD =0.346, 95%CI = 0.084–0.609, p = 0.010) levels as compared to inactive IBD and mild UC groups, respectively.

Conclusion

The overall level of serum lipids in IBD patients is lower than that of healthy individuals and is negatively associated with disease severity.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022383885.
Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19—A multicenter cohort study
Authors: Al Sulaiman Khalid , Korayem Ghazwa B. , Aljuhani Ohoud , Altebainawi Ali F. , Shawaqfeh Mohammad S. , Alarfaj Sumaiah J. , Alharbi Reham A. , Ageeli Mawaddah M. , Alissa Abdulrahman , Vishwakarma Ramesh , Ibrahim Alnada , Alenazi Abeer A. , Alghnam Suliman , Alshehri Nadiyah , Alshammari Maqbulah M. , Alhubaishi Alaa , Aldhaeefi Mohammed , Alamri Faisal F. , Syed Yadullah , Khan Raymond , Alalawi Mai , Alanazi Khalaf A. , Alresayes Faisal S. , Albarqi Khalid J. , Al Ghamdi Ghassan
Published: August 2023

Background

Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients.

Methods

A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate.

Results

A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87–1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00–0.47), p = 0.05 and beta coefficient 0.16 (95% CI −0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03].

Conclusion

The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.
Multi-omics analysis reveals the prognostic and tumor micro-environmental value of lumican in multiple cancer types
Authors: Guo Zehuai , Li Zeyun , Chen Ming , Qi Xiangjun , Sun Zhe , Wu Siqi , Hou Xuenan , Qiu Mengli , Cao Yang
Published: August 2023

Background: Lumican (LUM), a proteoglycan of the extracellular matrix, has been reported to be involved in the regulation of immune escape processes, but the data supporting this phenomenon are not sufficient. In this study, we aimed to explore the links among LUM expression, survival, tumor microenvironment (TME), and immunotherapy in 33 cancer types.

Methods: Data from several databases, such as UCSC Xena, GTEx, UALCAN, HPA, GEPIA2, TISIDB, PrognoScan, TIMER2, and GEO, as well as published studies, were used to determine the relationship between LUM expression and clinical features, TME, heterogeneity, and tumor stemness.

Results: The expression of LUM was statistically different in most tumors versus normal tissues, both at the RNA and protein expression levels. High expression of LUM was typically associated with a poor prognosis in tumors. Additionally, immune scores, six immune cells, four immunosuppressive cells, cancer-associated fibroblasts (CAFs)-associated and immunosuppressive factors, tumor mutation burden (TMB), microsatellite instability (MSI), DNAss, and RNAss were all significantly associated with LUM. Among them, LUM expression displayed a significant positive correlation with CAFs and their factors, and exhibited immunosuppressive effects in six independent immunotherapy cohorts.

Conclusion: Multi-omics analysis suggests that LUM may have been a prognostic marker, contributed to immunosuppression in the TME, and decreased the effectiveness of immune checkpoint inhibitors.
Neuroimaging anomalies in asymptomatic middle cerebral artery steno-occlusive disease with normal-appearing white matter
Authors: Huang Zhaodi , Xia Xiaona , Guan Shuai , Gong Gaolang , Luo Yishan , Shi Lin , Zhang Juntao , Meng Xiangshui
Published: August 2023

Background

Asymptomatic chronic cerebrovascular steno-occlusive disease is common, but the cognitive function and alterations in the brain’s structural and functional profiles have not been well studied. This study aimed to reveal whether and how patients with asymptomatic middle cerebral artery (MCA) steno-occlusive disease and normal-appearing white matter differ in brain structural and functional profiles from normal controls and their correlations with cognitive function.

Methods

In all, 26 patients with asymptomatic MCA steno-occlusive disease and 22 healthy controls were compared for neurobehavioral assessments, brain volume, cortical thickness, fiber connectivity density (FiCD) value, and resting-state functional connectivity (FC) using multimodal MRI. We also investigated the associations between abnormal cortical thicknesses, FiCD values, and functional connectivities with the neurobehavioral assessments.

Results

Patients performed worse on memory tasks (Auditory Verbal Learning Test-Huashan version) compared with healthy controls. Patients were divided into two groups: the right group (patients with right MCA steno-occlusive disease) and the left group (patients with left MCA steno-occlusive disease). The left group showed significant cortical thinning in the left superior parietal lobule, while the right group showed significant cortical thinning in the right superior parietal lobule and caudal portion of the right middle frontal gyrus. Increased FiCD values in the superior frontal region of the left hemisphere were observed in the left group. In addition, a set of interhemispheric and intrahemispheric FC showed a significant decrease or increase in both the left and right groups. Many functional connectivity profiles were positively correlated with cognitive scores. No correlation was found between cortical thickness, FiCD values, and cognitive scores.

Conclusion

Even if the patients with MCA steno-occlusive disease were asymptomatic and had normal-appearing white matter, their cognitive function and structural and functional profiles had changed, especially the FC. Alterations in FC may be an important mechanism underlying the neurodegenerative process in patients with asymptomatic MCA steno-occlusive disease before structural changes occur, so FC assessment may promote the detection of network alterations, which may be used as a biomarker of disease progression and therapeutic efficacy evaluation in these patients.
Extensive spinal epidural abscess due to Streptococcus intermedius: a case report treated conservatively and literature review
Authors: Liu Dianqi , Lu Weijie , Huang Wenbin , Zhai Wenrun , Ling Qinjie
Published: August 2023

Purpose

To describe the clinical significance of prompt, adequate, and targeted intravenous antibiotic (IV antibiotic) therapy in the successful management of spinal epidural abscess (SEA) associated with Streptococcus intermedius (S. intermedius) infection.

Case description

SEA is a rare, but catastrophic infection that may result in a high risk of permanent neurological disability. A 52-year-old Chinese female patient was presented to the emergency department due to 2 years of low back pain and 3 days of decreased muscle strength in the extremities. The blood culture confirmed the presence of S. intermedius infection, and gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated widespread epidural abscesses in the cervical, thoracic, and lumbar spine canal. Empirical IV antibiotic therapy with vancomycin was promptly initiated, with meropenem and moxifloxacin added subsequently based on blood culture results. After 5 days of IV antibiotic treatment, the patient’s blood culture became negative. 6 weeks later, a follow-up MRI showed a decrease in the size of the abscess. The patient’s muscle strength was mostly restored after 2 months of IV antibiotic treatment.

Conclusion

Repeat examinations or gadolinium-enhanced MRI should be considered when initial MRI findings are not diagnostic of SEA. For extensive SEA caused by Streptococcus intermedius infection, surgery may be non-essential, and the judicious antibiotic selection and adequate treatment duration are pivotal for successful conservative management. Furthermore, for patients who are not amenable to surgery, a comprehensive evaluation of their condition and meticulous implementation of a precise pharmacological regimen holds noteworthy clinical significance.
Fiducial markers in adjuvant setting for a patient affected by endometrial cancer: a case report
Authors: Titone Francesca , Restaino Stefano , Moretti Eugenia , Vullo Gianluca , Poli Alice , Arcieri Martina , Paglietti Chiara , Tonetto Fabrizio , Parisi Giuseppe , Barbui Elisa , Trovò Marco , Scambia Giovanni , Driul Lorenza , Vizzielli Giuseppe
Published: August 2023

Introduction

Intermediate-high and high-risk endometrial cancer often require adjuvant treatments such as radiotherapy (RT) or brachitherapy (BT) to reduce the risk of loco-regional relapse. Inter- and intra-fraction variability of internal pelvic anatomy are possibly the largest source of error affecting pelvic RT. The implantation of Fiducial Makers (FMs) in the vaginal cuff of patients receiving RT or BT could help patient daily setup, image guidance and intra-fraction detection of the radiation targets.

Clinical case

We have evaluated the case of an 80-year-old woman treated with surgery for endometrioid adenocarcinoma G2 (stage pT1b Nx LVSI+) who underwent adjuvant pelvic IMRT after the implantation of vaginal cuff FMs.

CT-simulation, Treatment Planning and IGRT strategy

Patient underwent planning CT scan 10 days after FMs implantation. RT consisted of 45Gy in 25 daily fractions to pelvic lymph nodes and surgical bed with simultaneous integrated boost up to 52.5Gy to the vaginal cuff and the upper two-thirds of the vagina. Cone beam Computed Tomography (CBCT) was acquired prior to every RT fraction for IGRT. Bladder and rectum were re-contoured on every CBCTs. Bladder and rectal volumes and median shifts were reported on a prospective database to quantify the impact of the pelvic organ variations.

Results

The patient reported no discomfort during the FMs implantation, and no complications were seen. No evidence of FMs migration was reported. Bladder and rectal volumes planned contours were 245 and 55.3cc. Median bladder volumes for approved and “not acceptable” CBCTs were 222cc (range: 130-398) and 131cc (range: 65-326), respectively. Median rectal volumes for approved and “not acceptable” CBCTs were 75cc (range: 58-117) and 90cc (range: 54-189), respectively. The median values of the anterior-posterior, superior-inferior, lateral direction shifts were 3.4, 1.8 and 2.11 mm, respectively.

Conclusion

In our clinical case, the implantation of FMs in the vaginal cuff of a patient who underwent pelvic adjuvant RT was well tolerated and reported no complications. The use of IGRT procedures based on FMs surrogating the vaginal vault may reduce inter-observer variability and pave the way for adaptive strategies or stereotactic treatments as external beam pelvic boost in gynecological field.
Case Report: Ribociclib-induced phototoxicity presented as dyschromia with subsequent bullae formation
Authors: Jhan Jyun-Yan , Wang Wei-En , Chu Sung-Chao , Cheng Chiu-Hsuan , Chang Chung-Hsing
Published: August 2023

Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana–Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient’s skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis.
Targeting collagen in tumor extracellular matrix as a novel targeted strategy in cancer immunotherapy
Authors: Liu Jiayang , Pan Danjie , Huang Xuan , Wang Songna , Chen Huaning , Zhu Yi Zhun , Ye Li
Published: August 2023

Collagen, the most abundant protein in mammal, is widely expressed in tissues and organs, as well as tumor extracellular matrix. Tumor collagen mainly accumulates in tumor stroma or beneath tumor blood vessel endothelium, and is exposed due to the fragmentary structure of tumor blood vessels. Through the blood vessels with enhanced permeability and retention (EPR) effect, collagen-binding macromolecules could easily bind to tumor collagen and accumulate within tumor, supporting tumor collagen to be a potential tumor-specific target. Recently, numerous studies have verified that targeting collagen within tumor extracellular matrix (TEM) would enhance the accumulation and retention of immunotherapy drugs at tumor, significantly improving their anti-tumor efficacy, as well as avoiding severe adverse effects. In this review, we would summarize the known collagen-binding domains (CBD) or proteins (CBP), their mechanism and application in tumor-targeting immunotherapy, and look forward to future development.
A bibliometric analysis of metastatic breast cancer: two-decade report (2002-2022)
Authors: Jiang Siyuan , Meng Qingjie , Ji Fuqing , Yin Yulong , Liu Xianghua , Shi Wenzhen , Lyu Yonggang
Published: August 2023

Background

MBC is a lethal form of breast cancer that arises when cancer cells invade other organs or tissues. The treatment of MBC needs personalized approaches based on the tumor and patient characteristics. The purpose of this paper is to analyze MBC studies from 2002 to 2022 using bibliometrics and to investigate its current situation, main contributors, core journals, highly cited papers, and topic evolution.

Materials and methods

We retrieved data from Web of Science Core Collection (WOSCC). Bibliometric analysis of the included literatures mainly used the following tools: the function of “analyze results” and “citation report” in WoS, Microsoft excel 2021, CiteSpace v.6.1. R6, VOSviewer v.1.6.18, BICOMB v.2.04 and gCLUTO v.1.0.

Results

We found 12,653 articles on MBC research published in 1, 802 journals by 69, 753 authors from 118 countries. The annual output and citation of MBC articles showed a rising trend over time. The United States was the most influential country in MBC research. The most cited journal in this field was The Journal of Clinical Oncology. And the most cited article was by Slamon DJ. The co-word analysis of keywords divides MBC into six research clusters. The hormone receptor-positive MBC and liquid biopsy of MBC are the frontiers research trends. “CDK4/6 inhibitor” had the highest burst strength.

Conclusion

Our bibliometric analysis offers a comprehensive overview of MBC research in the past two decades. It shows the current situation, main contributors, core journals, highly cited papers, and topic evolution of this field. Our study can assist researchers and practitioners to comprehend the development and trends of MBC research and to discover potential directions for future research.
Economic evaluations of artificial intelligence-based healthcare interventions: a systematic literature review of best practices in their conduct and reporting
Authors: Vithlani Jai , Hawksworth Claire , Elvidge Jamie , Ayiku Lynda , Dawoud Dalia
Published: August 2023

Objectives: Health economic evaluations (HEEs) help healthcare decision makers understand the value of new technologies. Artificial intelligence (AI) is increasingly being used in healthcare interventions. We sought to review the conduct and reporting of published HEEs for AI-based health interventions.

Methods: We conducted a systematic literature review with a 15-month search window (April 2021 to June 2022) on 17th June 2022 to identify HEEs of AI health interventions and update a previous review. Records were identified from 3 databases (Medline, Embase, and Cochrane Central). Two reviewers screened papers against predefined study selection criteria. Data were extracted from included studies using prespecified data extraction tables. Included studies were quality assessed using the National Institute for Health and Care Excellence (NICE) checklist. Results were synthesized narratively.

Results: A total of 21 studies were included. The most common type of AI intervention was automated image analysis (9/21, 43%) mainly used for screening or diagnosis in general medicine and oncology. Nearly all were cost-utility (10/21, 48%) or cost-effectiveness analyses (8/21, 38%) that took a healthcare system or payer perspective. Decision-analytic models were used in 16/21 (76%) studies, mostly Markov models and decision trees. Three (3/16, 19%) used a short-term decision tree followed by a longer-term Markov component. Thirteen studies (13/21, 62%) reported the AI intervention to be cost effective or dominant. Limitations tended to result from the input data, authorship conflicts of interest, and a lack of transparent reporting, especially regarding the AI nature of the intervention.

Conclusion: Published HEEs of AI-based health interventions are rapidly increasing in number. Despite the potentially innovative nature of AI, most have used traditional methods like Markov models or decision trees. Most attempted to assess the impact on quality of life to present the cost per QALY gained. However, studies have not been comprehensively reported. Specific reporting standards for the economic evaluation of AI interventions would help improve transparency and promote their usefulness for decision making. This is fundamental for reimbursement decisions, which in turn will generate the necessary data to develop flexible models better suited to capturing the potentially dynamic nature of AI interventions.
Research on the evolution of netizens’ comment focus in university online public opinion: KTF-BTM topic model with topic-temporal-focus framework
Authors: Zhang Yang , Lian Ji-Qing , Li Ren-De , Duan Hong-Tao
Published: August 2023

Nowadays, Study of comments in MicroBlog online public opinion is of great significance for relevant departments in managing public opinion, due to the increasing influence of online public opinion on the Internet. This paper presents a method for studying the evolutionary characteristics of netizens’ comment focus in university online public opinion. This method is based on a three-stage framework called Topic-Temporal-Focus. Firstly, in the topic mining stage, the KTF-BTM model is proposed for topic recognition, which effectively improves the quality of analysis. Secondly, in the temporal segmentation stage, time periods are divided into 4-hour intervals, and the identified topics are paired with each comment text to generate a topic-temporal list. Finally, in the focus recognition stage, the content and evolution patterns of netizens’ comment focus within shorter time sequences are explored by analyzing the data characteristics of the topic-temporal list. Experimental results show that the proposed KTF-BTM model significantly enhances topic recognition quality for short texts. The Topic-Temporal-Focus framework overcomes the challenge of sparse comment text data within shorter time periods and effectively classifies topic evolution within limited time sequences. This research work serves as a valuable contribution towards understanding the evolutionary characteristics of netizens’ focal points in university online public opinion.
Genetic analysis of heat tolerance in hot pepper: insights from comprehensive phenotyping and QTL mapping
Authors: TS Aruna , Srivastava Arpita , Tomar Bhoopal Singh , Behera Tusar Kanti , Krishna Hari , Jain Pradeep Kumar , Pandey Renu , Singh Bhupinder , Gupta Ruchi , Mangal Manisha
Published: August 2023

High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit abscission, thereby causing a significant reduction in yield. To unravel the intricate genetic mechanisms governing heat tolerance in hot pepper, an F2 population was developed through the crossing of two distinct genotypes exhibiting contrasting heat tolerance characteristics: DLS-161-1 (heat tolerant) and DChBL-240 (heat susceptible). The F2 population, along with the parental lines, was subjected to comprehensive phenotyping encompassing diverse morphological, physiological, and biochemical heat-related traits under high temperature conditions (with maximum temperature ranging from 31 to 46.5°C and minimum temperature from 15.4 to 30.5°C). Leveraging the Illumina Nova Seq-6000 platform, Double digest restriction-site associated DNA sequencing (ddRAD-seq) was employed to generate 67.215 Gb data, with subsequent alignment of 218.93 million processed reads against the reference genome of Capsicum annuum. Subsequent variant calling and ordering resulted in 5806 polymorphic SNP markers grouped into 12 LGs. Further QTL analysis identified 64 QTLs with LOD values ranging from 2.517 to 11.170 and explained phenotypic variance ranging from 4.05 to 19.39%. Among them, 21 QTLs, explaining more than 10% phenotypic variance, were identified as major QTLs controlling 9 morphological, 3 physiological, and 2 biochemical traits. Interestingly, several QTLs governing distinct parameters were found to be colocalized, suggesting either a profound correlation between the QTLs regulating these traits or their significant genomic proximity. In addition to the QTLs, we also identified 368380 SSR loci within the identified QTL regions, dinucleotides being the most abundant type (211,381). These findings provide valuable insights into the genetics of heat tolerance in hot peppers. The identified QTLs and SSR markers offer opportunities to develop heat-tolerant varieties, ensuring better crop performance under high-temperature conditions.
Physical activity and cognitive function in middle-aged adults: a cross-sectional analysis of the PATH through life study
Authors: Quinlan Clare , Rattray Ben , Pryor Disa , Northey Joseph M. , Cherbuin Nicolas
Published: August 2023

Objectives

Investigate the independent associations of objectively measured or self-reported physical activity at different intensities with cognitive performance in middle-aged adults.

Design

Cross-sectional.

Methods

156 middle-aged adults (age: 40.6 ± 1.5, 58.3% female) participated in the physical activity sub-study of the Personality and Total Health through life (PATH) project. Physical activity was measured objectively with the SenseWear™ armband (SWA), worn for seven consecutive days, and measured via self-report with a Physical Activity Recall survey (PAR). Cognitive performance was assessed with the Symbol Digit Modalities Test, the Digit Span Backwards, and an Immediate and Delayed Recall task. Associations between physical activity intensity and cognitive function were investigated in general linear models, controlling for age, sex, and education.

Results

Neither objectively measured nor self-reported physical activity were associated with cognitive function at light-, moderate-, vigorous-, or combined moderate-to-vigorous intensity in this cohort of well educated, healthy middle-aged adults. Sensitivity analyses with additional moderators (e.g., body mass index, hypertension, alcohol intake) and the use of composite cognitive measures did not alter the results.

Conclusion

In this cohort of middle-aged adults, objectively measured and self-reported physical activity do not appear to be associated with cognitive function. Longitudinal follow-ups utilising objective physical activity measures may be important in determining the impact of mid-life behaviours on the trajectory of cognitive changes into older age.
Integrating cognition in the laboratory with cognition in the real world: the time cognition takes, task fidelity, and finding tasks when they are mixed together
Authors: Carr Thomas H. , Arrington Catherine M. , Fitzpatrick Susan M.
Published: August 2023

It is now possible for real-life activities, unfolding over their natural range of temporal and spatial scales, to become the primary targets of cognitive studies. Movement toward this type of research will require an integrated methodological approach currently uncommon in the field. When executed hand in hand with thorough and ecologically valid empirical description, properly developed laboratory tasks can serve as model systems to capture the essentials of a targeted real-life activity. When integrated together, data from these two kinds of studies can facilitate causal analysis and modeling of the mental and neural processes that govern that activity, enabling a fuller account than either method can provide on its own. The resulting account, situated in the activity’s natural environmental, social, and motivational context, can then enable effective and efficient development of interventions to support and improve the activity as it actually unfolds in real time. We believe that such an integrated multi-level research program should be common rather than rare and is necessary to achieve scientifically and societally important goals. The time is right to finally abandon the boundaries that separate the laboratory from the outside world.
Development and validation of a scale for streaming dependence (SDS) of online games in a Peruvian population
Authors: Sairitupa-Sanchez Liset Z. , Collantes-Vargas Alejandra , Rivera-Lozada Oriana , Morales-García Wilter C.
Published: August 2023

Background

Addiction to online video game streaming has become one of the most appealing ways to occupy leisure time and is one of the most popular activities. The satisfaction it provides and the time invested in it are two of the main reasons why it is preferred. However, despite the clear benefits that this activity offers, in some cases, excessive use can lead to personal and/or family problems or abuse.

Objective

The objective of the study was to develop and validate a scale to measure potential traits of dependence on online game streaming. The participants were 423 Peruvian adults aged between 18 and 47 years (M = 22.87, SD = 5.02). The Streaming Dependence Scale (SDS) was developed based on a literature review, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted.

Results

The scale showed adequate internal consistency (α, CR, ω, and H > 80). Confirmatory analysis confirmed the one-dimensional structure (χ2 = 10.250, df = 5; p = 0.068; CFI = 0.98, TLI = 0.96, RMSEA = 0.06, SRMR = 0.05).

Conclusion

The brief SDS is a valid and reliable measure that can be used as a useful tool to identify and evaluate streaming dependence.