bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological histories govern social exploitation by microorganisms
Authors: Schaal Kaitlin A , Manhes Pauline , Velicer Gregory J
Published: December 2024

Exploitation is a common feature of social interactions, which can be modified by ecological context. Here, we investigate effects of ecological history on exploitation phenotypes in bacteria. In experiments with the bacterium Myxococcus xanthus, prior resource levels of different genotypes interacting during cooperative multicellular development were found to regulate social fitness, including whether cheating occurs. Responses of developmental spore production to manipulation of resource-level histories differed between interacting cooperators and cheaters, and relative-fitness advantages gained by cheating after high-resource growth were generally reduced or absent if one or both parties experienced low-resource growth. Low-resource growth also eliminated exploitation in some pairwise mixes of cooperative natural isolates that occurs when both strains have grown under resource abundance. Our results contrast with previous experiments in which cooperator fitness correlated positively with concurrent resource level and suggest that resource-level variation may be important in regulating whether exploitation of cooperators occurs in a natural context.
The role of sympathetic control in bone vasculature: insights from spinal cord injury
Authors: Sukhoplyasova Maria , Hamner Jason W , Draghici Adina E
Published: December 2024

Bone vasculature is richly innervated by an extensive network of sympathetic nerves. However, our understanding of bone blood flow regulation and its contribution to human bone health is limited. Here, we further our previous findings by characterizing bone vascular responses in the absence of sympathetic control—studying individuals with spinal cord injury (SCI), a population with known peripheral sympathetic disruption. We assessed tibial vascular responses to isometric handgrip exercise (IHE) in individuals with SCI (n = 12) and controls (n = 12). When sustained to fatigue, IHE increases perfusion pressure and sympathetic vasoconstriction in the nonactive tissues of the legs. During IHE, we measured blood pressure, whole leg blood velocity (LBV) via ultrasound, and tibial perfusion (as hemoglobin content) via near-infrared spectroscopy. Controls demonstrated active sympathetic vasoconstriction in the whole leg (ie, increased vascular resistance [VR], arterial pressure/LBV) and tibia (ie, decreased hemoglobin). In contrast, SCI individuals demonstrated modest whole leg vasoconstriction with lesser increases in VR than controls (p < .04). Tibial vasculature evidenced absent or blunted vasoconstriction compared to controls (p < .01), indicated by increasing tibial hemoglobin until plateauing at higher pressure levels. This suggests that, in the absence of sympathetic control, tibial vascular response may involve other regulatory mechanisms like myogenic vasoconstriction. Lastly, we leveraged existent whole-body DXA scans in a subgroup of 9 individuals with SCI, and we found a strong relationship between leg BMD and tibial hemoglobin at the end of IHE (r2 = 0.67, p < .01). Our findings indicate that in the absence of sympathetic mechanisms, myogenic control may play a compensatory role in regulating blood flow, though to a lesser extent in bone compared to muscle. The close relationship between lesser declines in bone blood content and higher BMD underscores the link between blood flow and bone health.
A deep intronic PHEX variant associated with X-linked hypophosphatemia in a Finnish family
Authors: Koponen Laura , Pekkinen Minna , Legebeke Jelmer , Muurinen Mari , Rusanen Salla , Hussain Shabir , Wang Fan , Nevalainen Pasi I , Mäkitie Outi
Published: December 2024

Hypophosphatemic rickets is a rare bone disease characterized by short stature, bone deformities, impaired bone mineralization, and dental problems. Most commonly, hypophosphatemic rickets is caused by pathogenic variants in the X-chromosomal PHEX gene, but autosomal dominant and recessive forms also exist. We investigated a Finnish family in which the son (index, 29 yr) and mother (56 yr) had hypophosphatemia since childhood. Both patients had typical clinical, radiographic, and biochemical features of hypophosphatemic rickets, including a pathological fracture in the son. Gene panels and whole-exome sequencing did not reveal any pathogenic variants in the known hypophosphatemia genes. Therefore, we performed whole genome sequencing and identified a deep intronic variant (c.2147 + 1197A > G) in PHEX. Both the affected individuals, but none of the unaffected family members, had the same variant, as confirmed by Sanger sequencing. According to RT-PCR, whole transcriptomic data, and in silico analyses, the variant led to a new splice donor site in intron 21 and an 84 basepair pseudoexon between exons 21 and 22, likely leading to the synthesis of abnormal PHEX protein. Our study underscores the importance of intronic PHEX variants in X-linked hypophosphatemia (XLH). In patients with features of XLH but negative gene panel or whole-exome sequencing results, the combination of whole-genome sequencing and whole transcriptomics should be considered to detect possible deep intronic variants. The methodologies presented have the potential to be used more widely in other rare diseases.
Increasing Number of Clinically Severe Mycoplasma pneumoniae Infections in Children After the COVID-19 Pandemic: A Single-Center Case Series
Authors: McCarthy Karen N , Hatcher James , Best Timothy , Kaliakatsos Marios , Hassell Jane , Turnbull Andrew , Sidgwick Peter , Gavela Javier , Simmonds Jacob , Kucera Filip , Warris Adilia , Kadambari Seilesh
Published: December 2024

In 2024, there have been increases in laboratory-confirmed infections caused by Mycoplasma pneumoniae worldwide. This case series highlights the increasing frequency of M. pneumoniae-positive PCR (polymerase chain reaction) specimens and an increased number of hospital admissions with M. pneumoniae clinical syndromes. Within this case series, we observed a change in the epidemiology and clinical burden of childhood M. pneumoniae disease in the post-COVID-19 era.
CICADA: a circRNA effort toward the ghost proteome
Authors: Fan Liyuan , Zhou Xinyuan , Li Mian , Gao Anwei , Yu Haojie , Tian Hui , Liao Liandi , Xu Liyan , Sun Liang
Published: December 2024

Recent studies have confirmed that certain circRNAs encode proteins that are integral to various biological functions. In this study, we present CICADA, an algorithm specifically designed to assess the protein-coding potential and coding products of circRNAs at high throughput, which enables the identification of previously unknown circRNA-encoded proteins. By harnessing the potential of this algorithm, we identified a variety of functional, protein-coding circRNAs in esophageal squamous cell carcinoma and established circRNA translation profiles for diverse types of cancer. This advancement innovatively explores the hidden proteome within the genome, poised to catalyze discoveries in biomarkers and therapies for cancers and complex diseases. CICADA is accessible as a Python module (https://github.com/SunLab-biotool/CICADA).
Cuproplasia-related gene signature: Prognostic insights for glioma therapy
Authors: Jue Toni Rose , Descallar Joseph , Pham Vu Viet Hoang , Bell Jessica Lilian , Shai-Hee Tyler , Cazzolli Riccardo , Nagabushan Sumanth , Koh Eng-Siew , Vittorio Orazio
Published: December 2024

Background

Adult-type diffuse gliomas encompass nearly a quarter of all primary tumors found in the CNS, including astrocytoma, oligodendroglioma, and glioblastoma. Histopathological tumor grade and molecular profile distinctly impact patient survival. Despite treatment advancements, patients with recurrent glioma have a very poor clinical outcome, warranting improved risk stratification to determine therapeutic interventions. Various studies have shown that copper is a notable trace element that is crucial for biological processes and has been shown to display pro-tumorigenic functions in cancer, particularly gliomas.

Methods

Differential gene expression, Cox regression, and least absolute shrinkage and selection operator regression were used to identify 19 copper-homeostasis-related gene signatures using TCGA lower-grade glioma and glioblastoma (GBM) cohorts. The GLASS Consortium dataset was used as an independent validation cohort. Enrichment analysis revealed the involvement of the signature in various cancer-related pathways and biological processes. Using this CHRG signature, a risk score model and a nomogram were developed to predict survival in glioma patients.

Results

Our prognostic CHRG signature stratified patients into high- and low-risk groups, demonstrating robust predictive performance. High-risk groups showed poorer survival outcomes. The nomogram model integrating CHRG signature and clinical features accurately predicted 1-, 3-, and 5-year survival rates in both training and test sets.

Conclusions

The identified 19-gene CHRG signature holds promise as a prognostic tool, enabling accurate risk stratification and survival prediction in glioma patients. Integrating this signature with clinical characteristics enhances prognostic accuracy, underscoring its potential clinical utility in optimizing therapeutic strategies and patient care in glioma management.
Frequency and impact of paediatric acute-onset neuropsychiatric syndrome/paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections diagnosis in Canada
Authors: Goren Rachel , Bitnun Ari , Doja Asif , Gill Peter J , Laxer Ronald M , Levy Deborah M , Pringsheim Tamara , Sandor Paul , Yeh Eluen Ann , Wilbur Colin , Kronenberg Sefi , Shouldice Michelle
Published: December 2024

Objectives

This study aims to estimate the prevalence of the PANS/PANDAS diagnostic label in Canada and describe its impact on families, patients, and health care.

Methods

Through the Canadian Paediatric Surveillance Program (CPSP), a monthly form was distributed to paediatricians from December 2019 to November 2021, requesting reports of children who received the diagnostic label of PANS/PANDAS between the ages of 3 and 18 years seen in the previous month. Descriptive and association statistical analyses were performed.

Results

Eighty-four cases (57% female, median age of symptom onset 7.8 years interquartile range [IQR] = 5) who received the diagnostic label of PANS/PANDAS were included. Prevalence was found to be 1 in 60,155 (0.0017%). Core diagnostic criteria for PANS/PANDAS (obsessive-compulsive disorder or tics or acute food refusal) were not present in 12% of cases (10/84). Only 22% reported sudden symptom onset. Infection was associated with symptom onset or exacerbation in less than one-third of cases. The majority exhibited two or more neuropsychiatric symptoms (95%). There was significant health care utilization and symptom burden amongst cases. There was a significant difference in the certainty of diagnosis between physicians and families (P < 0.05).

Conclusions

PANS/PANDAS diagnoses, while rare, significantly impact children, families, and the health care system. Diagnostic uncertainty underscores the challenges professionals and families face in accessing effective care, emphasizing the need for education and evidence-based clinical practice guidelines.
Generating fragrant oilseed rape using CRISPR/Cas9-mediated gene editing
Authors: Wu Jian , Xu Jingyi , He Ancheng , Ren Sichao , Ye Yi , Lei Wenjing , Liu Yu , Hua Xia , Wei Chunjie , Lin Li , Zhang Hui , Wang Youping
Published: December 2024

Knocking out 2 functionally redundant aldehyde dehydrogenase-encoding genes via gene editing leads to 2-acetyl-1-pyrroline accumulation in oilseed rape, which can be used to develop fragrant lines.
Superoxide anions induce tension wood formation by promoting cambium cell activity
Authors: Huang Li-Chao , Li Yu-Yu , Lai Jian-Xin , An Yi , Song Xue-Qin , Zhao Shu-Tang , Zhang Jin , Lu Meng-Zhu
Published: December 2024

Tension wood (TW), characterized by increased cambium cell proliferation and few vessels, is a classical model for the mechanical analysis of wood formation. In this study, we found higher superoxide anion (O2.−) levels in the cambium zone of poplar (Populus alba × P. glandulosa clone “84K”) TW than in that of opposite wood during gravistimulation. Treatment with an O2.− activator (methyl viologen) resulted in tension-wood-like xylem tissue formation, and transgenic plants with reduced cambium O2.− levels presented an attenuated gravity response. Time-course detection of O2.− and indole-3-acetic acid (IAA) levels revealed that auxin responses were enhanced following increases in O2.− levels, suggesting that IAA mediates TW induction downstream of O2.−. Rapid division but advanced programmed cell death in cambium cells was detected in both gravistimulated and O2.− activator-treated plants. These findings suggest that high O2.− levels trigger downstream IAA signaling to promote cambium cell proliferation and induce TW formation.
The Effects of Medical Debt Relief: Evidence from Two Randomized Experiments
Authors: Kluender Raymond , Mahoney Neale , Wong Francis , Yin Wesley
Published: December 2024

Two in five Americans have medical debt, nearly half of whom owe at least $2,500. Concerned by this burden, governments and private donors have undertaken large, high-profile efforts to relieve medical debt. We partnered with RIP Medical Debt (now Undue Medical Debt) to conduct two randomized experiments that relieved medical debt with a face value of $169 million for 83,401 people between 2018 and 2020. Our experiments focused on downstream medical debt that had been sold to debt collectors, and one of our experiments straddled an industry-wide pullback in the reporting of medical debt to the credit bureaus, allowing us to estimate the effects of debt relief with and without counterfactual reporting. We track outcomes using credit reports, collections account data, and a multimodal survey. There are three sets of results. First, we find a modest improvement in credit access when there is counterfactual credit reporting, but no impact on credit report outcomes when there is not. Second, we estimate that debt relief causes a moderate but statistically significant reduction in payments of existing medical bills. Third, we find no effects on survey measures of mental and physical health, healthcare utilization, and financial wellness. Taken together, our results indicate that the strong correlations documented in prior research do not translate into causal effects for downstream medical debt relief.
Representations on canonical models of generalized fermat curves and their syzygies
Authors: Karagiannis Kostas
Published: December 2024

We study canonical models of $\left(\mathbb{Z}/k\mathbb{Z}\right)^n$-covers of the projective line, tamely ramified at exactly n + 1 points each of index k, when $k,n\geq 2$ and the characteristic of the ground field K is either zero or does not divide k. We determine explicitly the structure of the respective homogeneous coordinate ring first as a graded K-algebra, next as a $\left(\mathbb{Z}/k\mathbb{Z}\right)^n$- representation over K and then as a graded module over the polynomial ring; in the latter case, we give generators for its first syzygy module, which we also decompose as a direct sum of irreducible representations.
Geocultural differences in preschooler sleep profiles and family practices: an analysis of pooled data from 37 countries
Authors: Zhang Zhiguang , Abdeta Chalchisa , Chelly Mohamed Souhaiel , del Pozo-Cruz Jesús , Draper Catherine E , Engberg Elina , Florindo Alex , Germana Leyna , Ghofranipour Fazlollah , Guan Hongyan , Ha Amy Sau-Ching , Hamdouchi Asmaa El , Tang Hong K , Hossain Mohammed Sorowar , Jambaldorj Bayasgalan , Kim Dong Hoon , Koh Denise , Kontsevaya Anna , Löf Marie , Lubree Himangi , Jáuregui Alejandra , Munambah Nyaradzai , Mwase-Vuma Tawonga , Oluwayomi Aoko , Pham Bang Nguyen , Reilly John J , Staiano Amanda E , Suherman Adang , Tanaka Chiaki , Tanui Stephen , Teo Wei-Peng , Tremblay Mark S , Turab Ali , Užičanin Edin , Veldman Sanne L C , Webster E Kipling , Wickramasinghe V Pujitha , Widyastari Dyah Anantalia , Okely Anthony
Published: December 2024

Study Objectives

To examine (1) multidimensional sleep profiles in preschoolers (3–6 years) across geocultural regions and (2) differences in sleep characteristics and family practices between Majority World regions (Pacific Islands, Sub-Saharan Africa, Eastern Europe, Northeast Asia, Southeast Asia, South Asia, the Middle East and North Africa, and Latin America) and the Minority World (the Western world).

Methods

Participants were 3507 preschoolers from 37 countries. Nighttime sleep characteristics and nap duration (accelerometer: n = 1950) and family practices (parental questionnaire) were measured. Mixed models were used to estimate the marginal means of sleep characteristics by region and examine the differences.

Results

Geocultural region explained up to 30% of variance in sleep characteristics. A pattern of short nighttime sleep duration, low sleep efficiency, and long nap duration was observed in Eastern Europe, Northeast Asia, and Southeast Asia. The second pattern, with later sleep midpoints and greater night-to-night sleep variability, was observed in South Asia, the Middle East and North Africa, and Latin America. Compared to the Minority World, less optimal sleep characteristics were observed in several Majority World regions, with medium-to-large effect sizes (∣d∣=0.48–2.35). Several Majority World regions reported more frequent parental smartphone use during bedtime routines (Northeast Asia, Southeast Asia: 0.77–0.99 units) and were more likely to have electronic devices in children’s bedroom (Eastern Europe, Latin America, South Asia: OR = 5.97–16.57) and co-sleeping arrangement (Asia, Latin America: OR = 7.05–49.86), compared to the Minority World.

Conclusions

Preschoolers’ sleep profiles and related family practices vary across geocultural regions, which should be considered in sleep health promotion initiatives and policies.
Association between genetic variation rs57095329 of microRNA-146a and development of cognitive impairment after anesthesia: a case–control study in a Chinese Han population
Authors: Fan Leijun , Wu Ru , Sun Yunyun , Li Xia , Chen Liang , Zhang Jun , Miao Chenghao
Published: December 2024

The latest studies have demonstrated that aberrant expression of microRNA-146a is related to cognitive decline. The rs57095329 polymorphism occurring in the miR-146a promoter modulates its expression and causes downstream pathogenicity. A case–control study in a Chinese Han population was established to investigate the genetic association between the miR-146a rs57095329 polymorphism and postoperative cognitive dysfunction (POCD). 242 patients with POCD and another 238 non-POCD cases were enrolled in the case–control study. Serum miR-146a levels were detected by qRT-PCR. miR-146a rs57095329 polymorphism was genotyped using the ABI PRISM SNaPshot method. The genetic association between the rs57095329 polymorphism and POCD was assessed by regression analysis. No significant difference was detected for age, gender and BMI between POCD and non-POCD groups. MiR-146a rs57095329 polymorphism revealed significant generic associations with POCD in both dominant and recessive models, and the AA genotype may increase the risk of developing POCD. qRT-PCR indicated the upregulation of miR-146a level in POCD group. Serum levels of miR-146a and inflammatory factors were higher in rs57095329 AA genotype carriers than in AG/GG genotype carriers. Rs57095329 polymorphism was independently associated with the development of POCD. In conclusion, miR-146a rs57095329 polymorphism was associated with POCD in the Chinese Han population. The rs57095329 AA genotype was the causative genotype for POCD and was related to the upregulation of miR-146a and inflammatory factor levels.
15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway
Authors: Jiang Fan , Yang Xiaoxiao , Shan Liqun , Miao Huiwen , Shi Chaohong
Published: December 2024

Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization. By utilizing 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, colony formation, transwell assays, and enzyme linked immunosorbent assay (ELISA), we investigated how 15d-PGJ2 affects A549 cell viability, proliferation, apoptosis, and invasion, as well as levels of interleukin (IL)-4, IL-13, and IL-17. Human monocytic cell line THP-1 was induced into M2 macrophages using phorbol 12-myristate 13-acetate and IL-4/IL-13, followed by treatment with 15d-PGJ2. The study employed flow cytometry to observe the polarization of macrophages, quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify epidermal growth factor receptor (EGFR) expression, western blot for identifying expression of macrophage marker proteins, and examining EGFR/rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf) activation. In a coculture setup, CD8+ T cells were shown to have a proliferation capacity by carboxifluorescein diacetate succinimidyl ester (CFSE), a killing ability by lactate dehydrogenase, and an analysis of their interferon gamma and tumor necrosis factor alpha levels by ELISA. 15d-PGJ2 reduced invasion capacity and expression of inflammatory cytokines, lowered A549 cell viability in a dose-dependent way, and promoted apoptosis. 15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8+ T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.
Pilot Feasibility Study of Physical Activity to Manage Bowel Dysfunction in Survivors of Rectal Cancer
Authors: Nehemiah Ariel , Pettke Erica , Appel Scott , Garcia David O. , Bea Jennifer W. , Thomson Cynthia A. , Sun Virginia , Krouse Robert S.
Published: December 2024

BACKGROUND:

Low anterior resection syndrome can disrupt health-related quality of life for survivors of rectal cancer.

OBJECTIVE:

To assess the feasibility, satisfaction with, and benefit of a pilot telehealth physical activity counseling intervention for survivors of rectal cancer with low anterior resection syndrome.

DESIGN:

Single site, single arm prospective pre-post pilot feasibility intervention.

SETTINGS:

This study was conducted at a single academic institution via telehealth.

PATIENTS:

Patients with stage I-III rectal or rectosigmoid cancer and low anterior resection syndrome who were 3 months to 5 years post-low anterior resection alone or with diverting loop ileostomy and subsequent reversal were included.

INTERVENTIONS(S):

Twenty-four patients completed 12 weekly one-on-one physical activity counseling sessions with a health coach.

MAIN OUTCOME MEASURES:

Feasibility, participant satisfaction, low anterior resection syndrome score, Memorial Sloan Kettering Cancer Center Bowel Function Instrument, International Physical Activity Questionnaire, City of Hope Quality of Life Survey – Colorectal Cancer, daily step counts.

RESULTS:

Twenty-seven patients enrolled in the study and 24 (89%) completed the intervention. Every intervention participant attended all telehealth coaching sessions. Through exit interviews, participants expressed satisfaction with the study, said it positively impacted their mental health, and helped them cope with their symptoms. At 12 weeks, 7.27% (p = 0.002) and 16.5% (p ≤ 0.0001) improvements in bowel function, as measured by the bowel function instrument and low anterior resection syndrome score, respectively were demonstrated. Quality of life improved by 9.8% at 12 weeks (p = 0.009), with the social domain having the greatest improvement (22%, p < 0.0001). These improvements persisted at twelve-week follow-up. Daily steps increased by 17.5% during the intervention (p = 0.035).

LIMITATIONS:

Pre-post study design.

CONCLUSIONS:

Delivering a telehealth counseling intervention is feasible and satisfactory for survivors of rectal cancer with LARS. This intervention has positive implications for bowel health and health-related quality of life. See Video Abstract.

Clinical Trial Registration:

NCT06435975.
Surprise Baby: Abdominoplasty Performed During Unknown Pregnancy
Authors: Lagumdzija Jasmina , Ender Sebastian , Mahrhofer Maximilian , Wechselberger Gottfried , Russe Elisabeth
Published: December 2024

Abdominoplasty is a commonly performed procedure for patients after significant weight loss and in postpregnancy women. Stable weight and completed family planning are critical for optimal outcomes, as pregnancy postabdominoplasty can increase risks for both mother and fetus and potentially compromise aesthetic results. We present the first reported case of a patient undergoing abdominoplasty while unknowingly pregnant. A 40-year-old woman, 4 years postbariatric bypass surgery, presented for abdominoplasty with a body mass index of 28 kg/m2. She had 3 children and had concluded her family planning. The surgery was performed without complications. Four months later, an unexpected pregnancy at 24 weeks was discovered. The patient developed gestational diabetes and hypertension but had no complications related to the abdominoplasty. The male newborn, delivered at 38 weeks, was small for gestational age but healthy. Ten years postsurgery, the patient maintained excellent aesthetic results with no abdominal complications. This case highlights that although family planning completion is recommended preoperatively to avoid complications, pregnancy postabdominoplasty can still result in favorable maternal and fetal outcomes. Although performing abdominoplasty on pregnant women is not advised, this case demonstrates that an undetected pregnancy during the procedure did not lead to adverse outcomes for the mother or child.
Vascular Basement Membrane Fragmentation in Keloids and the Expression of Key Basement Membrane Component Genes
Authors: Saijo Yusaku , Ichinose Shizuko , Dohi Teruyuki , Ogawa Rei
Published: December 2024

Background:

Keloids are growing scars that arise from injury to the reticular dermis and subsequent chronic local inflammation. The latter may be promoted by vascular hyperpermeability, which permits the ingress of chronic inflammatory cells/factors. Cutaneous capillaries consist of endothelial cells that generate, and are anchored by, a vascular basement membrane (VBM). Because VBM blocks immune cells/factors ingress, we investigated whether keloids are associated with altered VBM structure and/or VBM component expression by local endothelial cells.

Methods:

In total, 54 keloid (n = 27) and adjacent normal skin (n = 27) samples from 14 patients underwent transmission electron microscopy (TEM). Cross-sections of whole capillaries were identified. VBM thickness, continuity, and the number of layers in keloid and normal skin tissues were quantified. The differential expression of 222 previously reported VBM component genes in keloid and normal skin endothelial cells was analyzed using the GSE121618-microarray dataset.

Results:

TEM images showed that keloid VBMs were significantly thinner than adjacent skin VBMs (0.053 versus 0.078 nm; P < 0.001). They were also greatly fragmented (continuity was 46% versus 85% in normal skin; P < 0.001) and had fewer (1.2 versus 2.4) layers (P < 0.001). Keloidal endothelial cells demonstrated downregulation of 22 genes, including papilin, laminin-α5, and laminin-α2, and upregulation of 28 genes, including laminin-β1, laminin-β2, laminin-γ1, and laminin-γ2.

Conclusions:

VBMs are greatly fragmented in keloids. These changes support the notion that keloids are initiated/promoted, at least partly, by vascular hyperpermeability.
Retinitis Pigmentosa and Therapeutic Candidates
Authors: Livingston Chelsea A. , Weng Christina Y. , Chancellor John R.
Published: December 2024

Retinitis pigmentosa (RP) is a class of inherited retinal dystrophies (IRDs) that involves the degeneration of retinal photoreceptor cells and results in progressive vision loss. It was identified and named in 1857. For over 100 years, treatment of RP was generally limited to modifications in diet, management of cystoid macular edema, and supportive care for low vision. Over the last several decades, advances in technology and our understanding of the human genome have led to a host of new therapeutic candidates for the treatment of RP. This includes gene and cell therapy, optogenetics, neuroprotective agents, and electronic retinal implants. In this article, we summarize both the traditional and novel therapeutic modalities for the treatment of retinitis pigmentosa.
Comparing Teleretinal Screening-Identified Diabetic Retinopathy With Diabetic Nephropathy and Other Markers of Systemic Disease
Authors: Rodriguez Sean M. , Hamill Eric B. , Sundaresan Amritha , Guffey Danielle , Weng Christina Y.
Published: December 2024

Purpose:

Diabetic retinopathy and diabetic nephropathy are two major life-altering complications of diabetes mellitus. Identifying permissive and protective factors for diabetic retinopathy and nephropathy is imperative so that diabetic quality of life can be optimized and downstream complications can be minimized.

Methods:

We performed a large retrospective chart review of 997 patients at a county medical center with a majority Hispanic population. Through multivariable regression analysis, we identified significant factors associated with the presence of diabetic retinopathy or diabetic nephropathy. We also identified patients with a discordance between diabetic control and the severity of diabetic retinopathy and nephropathy.

Results:

Chronic kidney disease, baseline HbA1c, and systolic blood pressure were found to be positive risk factors for both diabetic retinopathy and diabetic nephropathy. Beta-blocker use and insulin use were identified as positive risk factors for diabetic retinopathy but not diabetic nephropathy. A higher body metabolic index (BMI) was found to be protective for diabetic retinopathy. We identified 7 patients with poor diabetic control (HbA1c >10%) but no diabetic retinopathy. There were no outlier patients found in the low glycemic exposure group.

Conclusions and Importance:

Our results are similar to other large-cohort reviews identifying factors associated with diabetic retinopathy and nephropathy. We identified a small cohort with discordance between diabetic control and the development of diabetic retinopathy or nephropathy. Future studies should be conducted looking into reasons for the anomalous progression of disease in certain patients.
Update on Management of Retinopathy of Prematurity: A Review
Authors: Chaaya Celine , Hoyek Sandra , Patel Nimesh A.
Published: December 2024

Retinopathy of prematurity (ROP) remains a significant health care concern in neonatal care as advances in neonatal intensive practices have improved the survival rates of premature infants. The management and screening of ROP have evolved significantly, with notable trends and advancements aimed at improving outcomes. The use of intravitreal antivascular endothelial growth factor injections has emerged as a prominent initial treatment for ROP in addition to laser photocoagulation. Screening practices have also seen enhancements, with a shift toward efficiency and tele-screening to optimize ROP management. This review aims to discuss available treatment and screening methods and explore new potential therapeutic tools for ROP.
The surgical safety margin after neoadjuvant chemotherapy combined with nimotuzumab leading to tumor regression
Authors: Zhang Suxin , Chen Si , Chai Guochao , Shi Yaoyao , Bao Yang , Peng Shixiong , Cui Zifeng , Hao Jiamei
Published: December 2024

Background:

To investigate the effect of nimotuzumab (N) combined with nab-paclitaxel, cisplatin, and fluorouracil (APF) neoadjuvant chemotherapy on the surgical margin.

Methods:

55 patients were divided into three groups: neoadjuvant chemotherapy and surgery group (G1, 15 cases), chemotherapy and surgery group (G2 group, 20 cases), and surgery group (G3 group, 20 cases). Tissue samples of the tumor core zone (P0), adjacent (P1, 3-5mm from tumor), distal adjacent (P2, 7-10mm from tumor), and surgical margin (P3, 15mm from tumor) were collected. Morphological changes and pathological remission rates were observed. Immunohistochemistry was used to detect the expression of EGFR, elF4E, P53, and VEGF in each specimen by statistical analysis.

Results:

In the G1 and G2 groups, various degrees of degeneration and necrosis were observed in the tumor retraction area. Nine cases of MPR (major pathologic response) and 4 cases of pCR (pathologic complete response) in the G1 group; 8 cases of MPR and 3 cases of pCR in the G2 group. The expressions of p53, eIF4E, and EGFR in the samples of the three groups decreased from P0 to P2 with statistical differences (p<0.05). In the molecular tumor shrinkage area, the expression levels of p53, eIF4E, and EGFR in the shrinkage zone were lower than those in the negative margin.

Conclusion:

In summary, although there is no significant statistical difference between neoadjuvant chemotherapy with nimotuzumab combined with APF and APF alone in the pathological remission rate of locally advanced oral squamous cell carcinoma, there is a trend indicating that nimotuzumab combined with APF is superior.
Probiotics prevent pegylated liposomal doxorubicin-associated hand-foot syndrome and oral mucositis of breast cancer patients following surgery and chemotherapy: a randomized placebo-controlled trial
Authors: Juan Zhang , Chen Jie , Ding Boni , Yongping Liang , Cai Haifeng , Chen Hui , Wang Ling , Le Yuan , Shi Jingcheng , Wu Yuhui , Ma Daqing , Ouyang Wen , Cheng Yong , Tong Jianbin
Published: December 2024

Background:

Hand-foot syndrome (HFS) and oral mucositis (OM) are common adverse events during cancer chemotherapy and can significantly decrease patients’ quality of life and chemotherapy adaptation, however, prevention strategies of these complications yet to be established.

Methods:

Patients with stages I–III breast cancer, who had surgery and needed pegylated liposomal doxorubicin (PLD)-based adjuvant chemotherapy were screened, recruited and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) treatment during the course of chemotherapy from November 2019 to August 2020. The incidence and severity of PLD related HFS and OM, and patients’ quality of life were assessed. Their plasma biomarkers, metabolites and fecal microbiota compositions were measured. And the results were further verified in animal experiments.

Results:

Probiotics supplement during PLD treatment significantly decreased the incidence and the severity of HFS and OM (P < 0.001), improved patients’ life quality (P < 0.001), increased the relative abundance of intestinal Enterococcus (P = 0.025) and mitigated the changes of seven plasma metabolites. Among these metabolites, the changes of p-Mentha-1,8-dien-7-ol (MDO) (B = − 0.441, P = 0.02) and L-arginine (B = − 0.586, P = 0.002) were negatively correlated with the occurrence of severe HFS and OM. MDO can partly reproduce the preventive effects of probiotics on PLD-related skin cell proliferating inhibition, DNA damage, and local inflammation in rats.

Conclusion:

Probiotics supplement during PLD-based chemotherapy prevents the incidence and severity of HFS and OM, which may be associated with modulating plasma metabolites including the MDO.
Lip-split mandibulectomy versus lip-mandible preservation technique for oral and oropharyngeal cancer: a systematic review and meta-analysis of comparative studies
Authors: Sun Bincan , Gan Chengwen , Tang Yan , Zhu Feiya
Published: December 2024

Background:

Many studies have compared lip-splitting mandibulotomy (LSM) and lip-mandible preservation (LMP) techniques in oral and oropharyngeal cancer (OOPC) patients with inconsistent conclusions. Evidence-based recommendations for the optimal surgical approach for treating OOPC are lacking.

Methods:

The Cochrane Library, Pubmed, Embase, Web of Science, WAN-FANG, CQVIP, and China National Knowledge Infrastructure were systematically searched to identify studies that compared LSM versus LMP for OOPC. An additional search of the gray literature was performed using Google Scholar, OpenGrey and ProQuest Dissertations & Theses Global. Survival rate, recurrence rate, surgical margin, perioperative outcomes, postoperative complications and functional status were assessed. The standard mean difference (SMD) and odds ratio (OR) with a 95% CI were pooled using fixed-effect or random-effect models.

Results:

Four randomized controlled trials, five case-control studies, and twenty cohort studies including a total of 2622 patients were identified. The LSM approach significantly increased postoperative complications such as mandibular osteomyelitis/osteoradionecrosis (OR = 4.57; 95% CI = 1.20-17.39; P = 0.026), fistula (OR = 1.5; 95% CI = 1.05-2.15; P = 0.027), and flap infection (OR = 2.96; 95% CI = 1.49-5.87; P = 0.002), while LMP improved facial appearance (SMD = −0.65; 95% CI = −1.05 to −0.25; P = 0.002). Meta-analyses showed no significant difference in survival rate (OR = 1.07; 95% CI = 0.83-1.38; P = 0.59), total recurrence (OR = 1.15; 95% CI = 0.87-1.52; P = 0.325), local recurrence (OR = 1.39; 95% CI = 0.88-2.19; P = 0.163), operation duration (SMD = 0.19; 95% CI = −0.75 to 1.13; P = 0.688), length of hospital stay (SMD = 0.48; 95% CI = −0.27 to 1.22; P = 0.208), volume of blood loss (SMD = 0.43; 95% CI = −0.17 to 1.03; P = 0.156), surgical margin (OR = 1.01; 95% CI = 0.72-1.41; P = 0.947), hematoma/seroma (OR = 1.01; 95% CI = 0.46-2.25; P = 0.972), wound infection (OR = 1.28; 95% CI = 0.92-1.79; P = 0.145), swallowing (SMD = −0.33; 95% CI = −0.91 to 0.24; P = 0.428) and speech (SMD = −0.14; 95% CI = −0.44 to 0.17; P = 0.381) between the LSM and LMP groups.

Conclusion:

These findings suggest that LMP may be a safe and efficient alternative to LSM for treating OOPC patients with decreased mandibular osteomyelitis/osteoradionecrosis, fistula, flap infection, and a better aesthetic outcome.
Cold scissors ploughing technique versus electrosurgical excision for hysteroscopic adhesiolysis: a multicenter randomized controlled trial
Authors: Liu Yichun , Xie Xiaoshi , Xue Pingping , Yuan Fang , Qi Yinghua , Wang Hui , Wang Ping , Lv Guanjun , Song Kejuan , Yang Zongzhi , Zhang Ya-Nan , Yan Lei
Published: December 2024

Intrauterine adhesions (IUAs) may lead to abnormal menstruation, infertility, and pregnancy-related complications. Hysteroscopic separation is the gold standard treatment for IUA and can be performed using a variety of instruments and methods, including cold scissors and electrotomy. However, it is unclear which method is more effective for relieving IUA, restoring uterine anatomy, and improving the pregnancy rate in women of childbearing age. This multicenter prospective randomized clinical trial included 218 women aged 20–40 years who were treated for IUA between 1 March 2021 and 30 June 2022 and followed for 1.5 years. The women were randomly assigned to a cold scissors group (n = 109) or electrosurgical excision group (n = 109). Second-look hysteroscopy was performed in all patients within 3–10 days after the end of the first postoperative menstrual period. The primary outcome was the change in American Fertility Society score. Secondary outcomes included postoperative menstrual blood loss, the recurrence rate, and the reproductive outcome. There was no significant difference in the curative effect of hysteroscopic adhesiolysis between the cold scissors group and the electrosurgical excision group (5 [interquartile range, 4–6] vs. 5 [interquartile range, 4–6], P = 0.729) or in the postoperative recurrence rate (27.5% vs. 30.6%, relative risk 0.901, 95% confidence interval 0.594–1.366, P = 0.623) or pregnancy outcomes between the two groups. Postoperative menstrual blood loss was significantly greater in the cold scissors group than in the electrosurgical excision group (65.1% vs. 48.1%, P = 0.029). The treatment cost was significantly lower in the cold scissors group (P < 0.001). In conclusion, hysteroscopic adhesiolysis using cold scissors does not differ significantly from electrosurgery in terms of treatment efficacy, recurrence rate, pregnancy rate, or pregnancy-related complications in patients with IUA who have normal ovarian reserve and an endometrial thickness of ≥6 mm before ovulation. The cold scissors ploughing technique can increase menstrual blood loss and is a cost-effective procedure.
Efficacy of laparoscopic parenchyma-sparing hepatectomy using augmented reality navigation combined with fluorescence imaging for colorectal liver metastases: a retrospective cohort study using inverse probability treatment weighting analysis
Authors: Zeng Xiaojun , Li Xinci , Lin Wenjun , Wang Junfeng , Fang Chihua , Pan Mingxin , Tao Haisu , Yang Jian
Published: December 2024

Background:

Laparoscopic parenchyma-sparing hepatectomy (PSH) is an effective treatment for colorectal liver metastases (CRLMs), but ensuring the safety and radicality of the procedure, particularly for deep-seated tumors, remains challenging. Surgical navigation technologies such as augmented reality navigation (ARN) and indocyanine green fluorescence imaging (ICG-FI) are increasingly utilized to guide surgery, yet their efficacy for CRLMs is unclear. This study aims to evaluate the short-term and long-term outcomes of ARN combined with ICG-FI-guided (ARN-FI) laparoscopic PSH for CRLMs.

Methods:

Between January 2020 and December 2022, 89 consecutive patients who underwent laparoscopic PSH for CRLMs were included in the study. Patients were divided into an ARN-FI group (n = 38) and a non-ARN-FI group (n = 51) based on the use of ARN-FI. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics and minimize potential selection bias. Short-term and long-term outcomes were compared between the two groups. Cox regression analysis was conducted to identify risk factors associated with recurrence-free survival (RFS) and hepatic RFS.

Results:

After IPTW, there were 87 patients in the ARN-FI group and 89 patients in the non-ARN-FI group. Shorter parenchymal transection time, postoperative hospital stays, and wider margins were observed in the ARN-FI group. There was no significant difference in RFS or hepatic RFS between the groups. Mutant KRAS status was an independent risk factor for both RFS and hepatic RFS, while tumor diameter ≥ 5 cm and deep-seated location were risk factors for hepatic RFS. In the subgroup analysis of deep-seated tumors, the ARN-FI group also showed less intraoperative blood loss, a lower rate of strategy change, shorter postoperative recovery times, a higher R0 resection rate, and improved RFS and hepatic RFS.

Conclusions:

In laparoscopic PSH for CRLMs, ARN-FI may improve surgical efficiency and accuracy. Especially for deep-seated tumors, it has the potential to reduce blood loss and attain higher R0 resection rates.
Systematic analysis of sugammadex-related adverse drug reaction signals using FAERS database
Authors: Liu Hongtao , Yang Qianqian , Li Zhaoyu , Yan Su , Ming Shaopeng
Published: December 2024

Background:

With the clinical integration of sugammadex, a selective relaxant-binding agent, the approach to reversing neuromuscular blockade is revolutionized. Despite its efficacy, sugammadex’s adverse reactions range from mild symptoms to severe cases, including anaphylaxis and coagulopathy. Assessing the nature of these reactions using the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database is vital for safe anesthetic practice. This study aimed to analyze and categorize the adverse drug events (ADEs) related to sugammadex reported in the FAERS database and evaluate the potential safety signals since its market entry.

Materials and methods:

This systematic analysis study extracted and filtered FAERS data pertinent to sugammadex from its introduction in 2008 to the last quarter of 2023 and employed standardized MedDRA terminologies for ADE re-encoding. The Reporting Odds Ratio (ROR) method analyzed ADE signal strength, identifying significant cardiovascular, allergic, and neurological signals.

Results:

From 1505 patient reports totaling 3562 ADEs, prominent adverse reaction signals were detected for respiratory and cardiovascular systems and severe allergic and neurological effects. Specific signals, including laryngospasm, bronchospasm, and Disseminated Intravascular Coagulation (DIC), among others, were highlighted and necessitated urgent clinical attention.

Conclusions:

Sugammadex is associated with a spectrum of adverse reactions, some of which demand increased clinical surveillance, particularly in older and pediatric populations. The significance of allergic reactions, airway spasms, and coagulation events indicates the need for precise risk assessment and vigilant monitoring during clinical use.
Associations of osteoarthritis with risk of future fracture events: prospective study in UK Biobank
Authors: Wang Ping , Tang Zijun , Lin Xiaoyu , Shao Wenkai , Wang Bo , Li Zilin , Lv Xiao , Liu Gang , Feng Yong
Published: December 2024

Background:

Researchers have long been interested in the potential relationship between osteoarthritis (OA), falls, and fractures; however, the evidence supporting this relationship has been conflicting. This study aimed to investigate the association between osteoarthritis and future fracture events.

Materials and methods:

This study was designed as a prospective cohort study. We recruited a total of 440 476 individuals from the UK Biobank to investigate the impact of OA on the incidence of fracture. Among the total population, there were 54 581 participants diagnosed with OA. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results:

A total of 26 083 fracture events were documented over a median follow-up period of 13.5 years. After multivariable adjustment, participants with osteoarthritis had an HR (95% CI) of 1.11 (1.08, 1.15) for future fracture events compared to participants without osteoarthritis (P < 0.0001). Falls explained 16.34% of the association between osteoarthritis and fracture events and 14.15% of the association between knee osteoarthritis and fracture events. The association was not substantially altered across the series of sensitivity analyses.

Conclusion:

Osteoarthritis was associated with a greater risk of future fracture events. This finding highlights the importance of preventing future fracture events in people with osteoarthritis.