bluuebunny/crossref_metadata_2025 huggingface dataset:
Arthroscopic-assisted uni-portal ligament flavum sparing bone anchoring annular suture technique for lumbar disc herniation: A case report and literature review
Authors: Xia Gushang , Song En , Kong Qingli , Li Xianglin
Published: September 2024

Rationale:

Lumbar disc herniation (LDH) manifests in diverse forms. If the nucleus pulposus or endplate tissues protrudes, the location of annular tears also varies, which poses various challenges for the annular suture technique. Tears at the annular attachment area at the edge of the vertebral body (cephalad or caudad) are considered a prohibitively challenging area for annular suturing.

Patient concerns:

A 37-year-old woman presented with a gradual onset of symptoms, experiencing leg pain and numbness over the left leg for 1 year before presentation. The pain radiated to the left S1 dermatome. Despite undergoing continuous medical therapy for more than 6 months, her symptoms showed no improvement. The strength of the left plantar flexion in the ankle and great toe was rated at 4 out of 5. The straight leg-raising and strengthening tests were positive for the left sides. Lumbar computed tomography and magnetic resonance imaging revealed left-sided disc herniation at the L5–S1 level, and nerve root compression, confirming the diagnosis of LDH.

Diagnoses:

The preoperative impression was LDH, intraoperative confirmation of a tear in the annular attachment area at the vertebral body edge.

Interventions:

This patient was treated with an arthroscopic-assisted uniportal spinal surgery (AUSS) technique focusing on ligament flavum (LF) preservation, protruding nucleus pulposus removal, nerve root decompression, and vertebral edge tear was then sutured using a bone anchoring annular suture with the Smile suture device.

Outcomes:

This technique was performed successfully in a patient with LDH. Significant improvements were observed in postoperative pain and numbness, Visual Analog Scale, and Japanese Orthopaedic Association scores. No postoperative instability or complications were observed, with computed tomography and magnetic resonance imaging confirming complete decompression. To the best of our knowledge, this is the first used AUSS with LF preservation and bone anchoring annular suture technique for LDH.

Lessons:

This case study demonstrates the AUSS combined with LF preservation and the bone anchoring annular suture technique provides favorable clinical and imaging outcomes and is a safe and effective technique for the treatment of LDH.
Small bowel Crohn’s disease neglected by gastroenterologists and anorectal surgeons with a 7-year delay in diagnosis: A case report
Authors: Shen Jiayan , Huang Yingshuang , Wang Weiwei , Ke Rubin , Fan Xiuqin
Published: September 2024

Rational:

Small bowel Crohn’s disease (SBCD) is a common site of Crohn’s disease (CD). However, owing to the anatomical characteristics of the small bowel and the limitations of traditional examination methods, the detection and diagnosis of SBCD remain difficult. Gastroenterologists and anorectal surgeons should pay more attention to improving the early diagnosis rate, so as to improve the prognosis of patients and reduce the probability of surgery due to complications.

Patient concerns:

Here, we presented a case of a young male with severe localized pain in the right kidney area and fever but no weight loss or diarrhea, who had a history of perianal abscess surgery 7 years ago and an elevated platelet count reviewing his previous medical examination report.

Diagnoses:

SBCD was not diagnosed until complications of intestinal fistula developed 7 years after perianal abscess surgery.

Interventions:

Anti-infection treatment was administered due to elevated inflammatory markers and evidence of infection on computed tomography scan, and exclusive enteral nutrition (EEN) was then performed because of the diagnosis of SBCD. Although the infection was absorbed by the treatment with EEN, a laparoscopic modified partial enterectomy was finally performed due to the complication of intestinal fistula.

Outcomes:

The patient was discharged on the seventh postoperative day without postoperative complications and started biologic therapy 2 weeks after surgery because he had high-risk factors for postoperative recurrence. The pathological report revealed the involvement of the ileum in CD, and confirmed the existence of the intestinal fistula.

Lessons:

Gastroenterologists and anorectal surgeons should be aware that perianal abscess could be the first manifestation of SBCD; even if typical CD manifestations are absent, proper further examinations are necessary based on the comprehensive analysis of clinical data of patients. In addition, the platelet count deserves attention in patients with potentially possible CD. More importantly, it is important to emphasize the importance of EEN in adult CD patients.
Rare symptom of left inguinal abscess secondary to a retroperitoneal perforation of diverticulitis of the sigmoid colon: A case report
Authors: Nihei Mio , Kamada Teppei , Aida Takashi , Yamagishi Daisuke , Takahashi Junji , Nakashima Keigo , Ito Eisaku , Suzuki Norihiko , Hata Taigo , Yoshida Masashi , Ohdaira Hironori , Suzuki Yutaka
Published: September 2024

Rationale:

Complicated colorectal diverticulitis could be fatal, and an abscess caused by this complication is usually formed at the pericolic, mesenteric, or pelvic abscess. Therefore, we report a rare case of sigmoid colon diverticulitis that developed a large inguinal abscess.

Patient concerns:

A woman in her 70s was admitted to our hospital with a chief complaint of left inguinal swelling and tenderness 1 week before admission. Physical examination showed swelling, induration, and tenderness in the left inguinal region. Blood tests revealed elevated inflammatory reaction with C-reactive protein of 11.85 mg/dL and white blood cells of 10,300/μL. Contrast-enhanced computed tomography showed multiple colorectal diverticula in the sigmoid colon, edematous wall thickening with surrounding fatty tissue opacity, and abscess formation with gas in the left inguinal region extending from the left retroperitoneum.

Diagnoses:

The diagnosis was sigmoid colon diverticulitis with large abscess formation in the left inguinal region.

Interventions:

Immediate percutaneous drainage of the left inguinal region was performed, as no sign of panperitonitis was observed. Intravenous piperacillin-tazobactam of 4.5 g was administered every 6 hours for 14 days.

Outcomes:

The inflammatory response improved, with C-reactive protein of 1.11 mg/dL and white blood cell of 5600/μL. Computed tomography of the abdomen confirmed the disappearance of the abscess in the left inguinal region, and complete epithelialization of the wound was achieved 60 days after the drainage. The patient is under observation without recurrence of diverticulitis.

Lessons:

We report a rare case of sigmoid colon diverticulitis that developed a large inguinal abscess, which was immediately improved by percutaneous drainage and appropriate antibiotics administration.
Nutrition literacy and eating habits in children from food-secure versus food-insecure households: A cross-sectional study
Authors: Hashemzadeh Maral , Akhlaghi Masoumeh , Akbarzadeh Marzieh , Nabizadeh Kiana , Miri Hamid Heidarian , Kazemi Asma
Published: September 2024

This study aimed to explore whether maternal food and nutrition literacy (FNL) can mitigate negative effects of food insecurity on children’s eating habits and assist food-insecure households in making better nutrition choices with limited resources available. A cross-sectional study was conducted on children aged 6 to 12 years and their mothers. FNL was assessed using a validated Food and Nutrition Literacy Assessment Tool, and household food security was evaluated with the Household Food Insecurity Access Scale. Eating habits were measured through a structured questionnaire that focused on various dietary habits. Logistic regression was used to determine the associations between maternal FNL, food insecurity status, and children’s eating habits. A total of 327 children–mothers, comprising 159 food-secure and 168 food-insecure households, were evaluated. Maternal FNL was inversely associated with consumption of fast-foods and fried foods, and skipping breakfast in both food-secure and food-insecure participants. However, only food-secure participants showed an inverse association between FNL and the habit of eating out. Both groups indicated lower sweet consumption associated with higher FNL. Maternal FNL was inversely associated with lower dairy and nut intake in food-secure group and lower fruit and vegetable consumption in food-insecure participants. This study suggests that in conditions of food insecurity FNL may reduce the negative impact of food insecurity on children’s nutrition choices and food habits.
Probe into the treatment of tinnitus by acupuncture combined with medicine under the mechanism of pathophysiology: A review
Authors: Hu Wenhui , Xu Dongye , Xing Qingchang
Published: September 2024

Tinnitus is a common medical disorder. The risk factors include hearing loss, ototoxic medications, head injuries, and depression. Therefore, ear disorders, anxiety, and depression should be considered in the treatment of tinnitus. Although considerable research has been conducted on the pathogenesis and treatment of tinnitus, there is currently no effective treatment. Traditional Chinese medicine (TCM) has a certain effect on tinnitus and a large number of clinical trials have been conducted. Its treatment methods vary and include TCM, acupuncture, and music therapy. TCM treatment of tinnitus usually takes the method of comprehensive treatment, not only relying on drugs but also safety. Therefore, this review explores the treatment of tinnitus using acupuncture combined with medicine, based on the new pathophysiological mechanism of tinnitus.
Relationship between the triglyceride-glucose index and depression in individuals with chronic kidney disease: A cross-sectional study from National Health and Nutrition Examination Survey 2005–2020
Authors: Liu Demin , Wei Danxia
Published: September 2024

Accumulating evidence indicates that individuals with chronic kidney disease (CKD) are at an increased risk of experiencing depressive disorders, which may accelerate its progression. However, the relationship between the triglyceride-glucose (TyG) index and depression in CKD individuals remains unclear. Therefore, this cross-sectional study aimed to assess whether such a relationship exists. To this end, the CKD cohort of the National Health and Nutrition Examination Survey from 2005 to 2020 was analyzed using multivariable logistic regression analyses and a generalized additive approach. A recursive algorithm was employed to pinpoint the turning point, constructing a dual-segment linear regression model. The study included 10,563 participants. After controlling for all variables, the odds ratios and 95% confidence intervals indicated a 1.24 (range, 1.09–1.42) relationship between the TyG index and depression in the CKD cohort. The findings underscored an asymmetrical association, with a pivotal value at a TyG index 9.29. Above this threshold, the adjusted odds ratio (95% confidence interval) was 1.10 (range, 0.93–1.31). This relationship was significant among the obese subgroups. The study results highlight the complex relationship between the TyG index and depression among American adults with CKD.
Global trends and hotspots in research of paronychia: A bibliometric analysis
Authors: Zhou Chaoxi , Yu Guangrong , Wang Qinglei , Yang Zhaoyi , Wang Huimin , Zhao Yongzhen
Published: September 2024

Background:

Paronychia is a prevalent clinical disease profoundly affecting patients’ quality of life. As ongoing evolution in modern living environments, factors contributing to paronychia are becoming increasingly diverse. Therefore, a further understanding about latest trend of paronychia is imperative and pressing.

Methods:

A systematic literature search was performed based on Web of Science Core Collection and Science Citation Index Expanded. The search parameters encompassed keywords associated with paronychia from 1980 to 2023, and rigorous data cleaning procedures were executed to maintain the analysis’s relevance and dependability, supplemented by a thorough examination of abstracts and titles. Visibility analysis was conducted with Citespace and VOSviewer tools to explore the publication trends, collaborative networks, and impactful studies.

Results:

A total of 595 articles were included in this study. The annual publication trends exhibited a significant increase since 1990, reached a peak of 41 articles in 2021. Collaborative relationships among countries demonstrated strong connections, with the United States leading in both publication volume, citation records and international cooperation. Keyword analysis indicated that in recent years, a substantial body of research has concentrated on paronychia issues caused by epidermal growth factor receptor inhibitors (EGFRI)-class drugs, such as Gefitinib, Erlotinib, and Afatinib, in the context of tumor treatment.

Conclusion:

In this area, most of the recent hotspots are not focused on the basic research about paronychia due to the basic research about traditional paronychia already reached a relative mature stage. However, with the widespread clinical application of EGFRI anticancer drugs, the incidence of drug-induced paronychia is inevitably on the rise. Therefore, with the expanding diversity in the etiology of paronychia, this area deserves a multiple discipline cooperation with a much wider international communication.
Assessment of human health risk induced by 7 metals exposure through drinking water in Urumqi, Xinjiang, China
Authors: Li Jie , Ding Guanxin , Lin Qin
Published: September 2024

Heavy metal water pollution refers to the abnormal concentration of metal elements and their compounds in water with a relative density of >4.5, which causes the water quality to decline or deteriorate. To assess the presence of 7 metals in drinking water in a city in Xinjiang and the health risks to the human body caused by drinking the water and to provide a scientific basis for health risk management for drinking water. In 2021, 114 monitoring points were set up in Urumqi, Xinjiang, China, and 228 water samples were collected in the dry and in the wet seasons to monitor water quality. Using the Standards for drinking water quality (GB 5749-2006), the concentrations of 7 metals were measured, and a method recommended by the United States Environmental Protection Agency was used to assess health risks. A total of 228 water samples were collected and measured, and 227 met the standard, for a compliance rate of 99.56%. Except for Mn, the compliance rates for the other 6 metals were 100%. Based on noncarcinogenic health risk, the order of the 7 metals was Al > Fe > Gu > Mn > Hg > Zn > Pb, and the hazard index was 3.33 × 10‐7 < 1. The total noncarcinogenic health risk of 7 metals was <1, that is, within the acceptable range. Al has the highest noncarcinogenic health risk, followed by Fe.
Unveiling the glycolysis in sepsis: Integrated bioinformatics and machine learning analysis identifies crucial roles for IER3, DSC2, and PPARG in disease pathogenesis
Authors: Cui Dongqing , Yu Tian
Published: September 2024

Sepsis, a multifaceted syndrome driven by an imbalanced host response to infection, remains a significant medical challenge. At its core lies the pivotal role of glycolysis, orchestrating immune responses especially in severe sepsis. The intertwined dynamics between glycolysis, sepsis, and immunity, however, have gaps in knowledge with several Crucial genes still shrouded in ambiguity. We harvested transcriptomic profiles from the peripheral blood of 107 septic patients juxtaposed against 29 healthy controls. Delving into this dataset, differential expression analysis shed light on genes distinctly linked to glycolysis in both cohorts. Harnessing the prowess of LASSO regression and SVM-RFE, we isolated Crucial genes, paving the way for a sepsis risk prediction model, subsequently vetted via Calibration and decision curve analysis. Using the CIBERSORT algorithm, we further mapped 22 immune cell subtypes within the septic samples, establishing potential interactions with the delineated Crucial genes. Our efforts unveiled 21 genes intricately tied to glycolysis that exhibited differential expression patterns. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses offered insights, spotlighting pathways predominantly associated with oxidative phosphorylation, PPAR signaling pathway, Glycolysis/Gluconeogenesis and HIF-1 signaling pathway. Among the myriad genes, IER3, DSC2, and PPARG emerged as linchpins, their prominence in sepsis further validated through ROC analytics. These sentinel genes demonstrated profound affiliations with various immune cell facets, bridging the complex terrain of glycolysis, sepsis, and immune responses. In line with our endeavor to “unveil the glycolysis in sepsis,” the discovery of IER3, DSC2, and PPARG reinforces their cardinal roles in sepsis pathogenesis. These revelations accentuate the intricate dance between glycolysis and immunological shifts in septic conditions, offering novel avenues for therapeutic interventions.
Emapalumab as a therapeutic intervention for Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis: A case series
Authors: Wang Wen , Yuan Xiao , Yu Li , Pei Fuyu
Published: September 2024

Rationale:

Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by a severe cytokine storm, heightened inflammatory response, and immune-mediated damage to tissues and organs. Standard treatment protocols for hemophagocytic lymphohistiocytosis often fall short in effectively controlling EBV-HLH, leading to a need for novel therapeutic options. Emapalumab, a monoclonal antibody targeting interferon-gamma, has shown promise due to its targeted cytokine modulation capabilities and favorable safety profile. This study aimed to evaluate the efficacy and safety of emapalumab in pediatric patients with EBV-HLH.

Patient concerns:

The case series involved 4 pediatric patients diagnosed with EBV-HLH who did not achieve disease control despite receiving comprehensive treatment.

Diagnoses:

All 4 pediatric patients were diagnosed with EBV-HLH.

Interventions:

Emapalumab was introduced as an adjunctive therapeutic intervention alongside the HLH-94 or L-DEP regimens for these patients.

Outcomes:

Among the 4 patients, 1 experienced severe multiorgan dysfunction and opted to discontinue therapy. The remaining 3 patients showed controlled disease progression with significant clinical improvements following emapalumab administration. These improvements included reduced levels of inflammatory markers, normalization of blood counts and liver function, and decreased Epstein–Barr virus viral load.

Lessons:

The findings suggest that emapalumab may be an effective and safe treatment option for pediatric EBV-HLH. However, further research is necessary to confirm these outcomes, especially in critically ill patients.
The potential causal relationship between BMI, T1D, urolithiasis, and hydronephrosis in European ancestry: A Mendelian randomization analysis
Authors: Han Yangjun , Gao Wenzhi , Wang Bing , Gao Zihui , Diao Mingxin , Zuo Chao , Zhang Minghua , Diao Yingzhi , Wang Chunji , Liu Honglei , Gu Yaming
Published: September 2024

Body mass index (BMI), type 1 diabetes (T1D), urolithiasis, and hydronephrosis are interrelated. Our aim was to analyze their causal relationships at the genetic level. Mendelian randomization is an instrumental variable analysis method that follows Mendel genetic law of random allocation of parental alleles to offspring. In observational studies, genetic variants are used as instrumental variables to infer causal relationships between exposure factors and study outcomes. All the genome-wide association study data in our study were publicly available and from published genome-wide association studies, UK Biobank, and FinnGen. Random-effects inverse variance weighted was the primary analysis method, with R Egger, weighted median, and weighted mode as supplementary methods. We examined heterogeneity, horizontal pleiotropy, and the influence of individual single nucleotide polymorphisms on the analysis. We further explored the causal relationships between BMI, T1D, urolithiasis, and hydronephrosis, as well as the robustness of the analysis results. Inverse variance weighted results showed genetic causal relationships between BMI (P = .034, odds ratio [OR] 95% confidence interval [CI] = 1.273 [1.019–1.589]), T1D (P = .028, OR 95% CI = 0.921 [0.855–0.991]), urolithiasis (P < .001, OR 95% CI = 1.361 [1.175–1.576]), and hydronephrosis. Sensitivity analyses confirmed the accuracy and robustness of these findings. Our results support significant causal roles of BMI, T1D, and urolithiasis in hydronephrosis, potentially offering new intervention strategies for preventing its development.
Prevalence of genetically diagnosed familial hypercholesterolemia in Vietnamese patients with premature acute myocardial infarction
Authors: Nguyen Kha Minh , Hoang Sy Van
Published: September 2024

Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated low-density lipoprotein cholesterol (LDL-C) levels, which manifest early in the first decades of life. It is a major cause of premature coronary artery disease worldwide, leading to significant public health challenges. The prevalence of genetically determined FH in patients with premature coronary artery disease remains underestimated, particularly in developing countries. This study aimed to assess the prevalence of genetically defined FH in Vietnamese patients with premature acute myocardial infarction (AMI) in the Vietnamese population. This cross-sectional study enrolled 218 consecutive patients diagnosed with premature AMI who underwent coronary angiography. The low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 genes were analyzed by next-generation sequencing. FH was diagnosed according to Dutch Lipid Clinic Network criteria. Among the patients with premature AMI who underwent coronary angiography, the mean age was 46.9 ± 6.1 years, with a predominance of males (83.9%). The prevalence of potential FH diagnosed using Dutch Lipid Clinic Network criteria was 14.7% (definite FH, 6.0%; probable FH, 8.7%). Pathogenic or likely pathogenic variants in LDLR, apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 were found in 9 of 218 patients (4.1%), all of which were causative mutations in LDLR. Patients with premature AMI and FH had significantly greater LDL-C levels (217.6 vs 125.7 mg/dL) and more severe coronary artery lesions, as assessed by the Gensini score (100.3 vs 60.5), than did those in the No FH group. The prevalence of genetically determined FH among Vietnamese patients with premature AMI is relatively high. Screening and diagnosis of hereditary conditions in patients with premature AMI are essential to improve early detection and management and reduce the burden of coronary artery disease in this population.
From clinical development to real-world outcomes with inclisiran
Authors: Connolly Derek L. , Sharma Vinoda , Ray Kausik K.
Published: September 2024

Purpose of review

Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.

Recent findings

To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events

Inclisiran has been evaluated in numerous trials, primarily the ORION 926, ORION 1027 and ORION 1128 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.
Quality indicators prospectively associated with falls in inpatient rehabilitation facilities
Authors: Wright Jonathan Robert , D’Ausilio Jamie , Cappaert Thomas , Lau Jeffery D.
Published: September 2024

Objective

Retrospective studies suggest quality indicators (QI) are associated with falls in inpatient rehabilitation facilities (IRFs), but this claim has not yet been validated prospectively. The aim of this study was to analyze the associations between QI codes and falls in a prospective sample.

Design

For this prospective observational cohort study, we followed 658 patients from 4 IRFs who were consecutively admitted and discharged over a 6-month period. On admission, we collected patients’ QI codes, and then, tracked whether they fell during their IRF stay.

Results

Univariable logistic regressions revealed that most individual QI items for communication, self-care, and mobility were significantly associated with falls. In a multivariable model with 6 different QI items, only patients’ performance going up and down 1 step was significantly associated with falls. To explain this finding, we investigated the relationships between these QI items and found 3 of them to be highly correlated.

Conclusions

Most individual QI items appear prospectively associated with falls. Patients with lower QI codes are more likely to fall. Combining QI items (such as expression and toileting) may improve fall-risk assessment, but some QI items may be too interrelated to use together.
Estimating the prevalence of Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) – a systematic review
Authors: Ward Joseph A. , Calderbank Thomas , Tang Chee Chee , Goddard Naveen V , MacNeill Fiona A , Tasoulis Marios K , Khan Aadil A.
Published: September 2024

Introduction:

Assessment of BIA-ALCL prevalence is challenged by a lack of population-level data for the prevalence of breast implants in the wider population. Absence of such data obscures the true prevalence of BIA-ALCL and hinders informed consent consultations. We performed a systematic review to synthesise data from published studies reporting BIA-ALCL cases in defined patient populations to better inform the evidence base.

Methods:

PubMed and Embase were searched to obtain studies reporting the prevalence of BIA-ALCL in defined patient cohorts with breast implants where case prevalence was calculable. Study characteristics, the number of BIA-ALCL cases and total sample size were extracted and used to calculate the prevalence of BIA-ALCL per 100,000 implanted patients.

Results:

Of 1,477 publications identified by the search, 38 studies incorporating 28 cohort and 6 registry studies satisfied the inclusion criteria encompassing a total population sample of 17,038,371 patients and 1,170 BIA-ALCL patients. The prevalence of BIA-ALCL was found to be 30.54 per 100,000 implanted patients with textured implants (1 case per 3,274 implanted patients) and 6.70 per 100,000 implanted patients with implants of any-type (1 case per 14,925 implanted patients).

Conclusions:

By synthesising the published literature, this work provides a determination of BIA-ALCL prevalence using study- and population-level data where the prevalence of breast implants is known. The accurate determination of BIA-ALCL prevalence is of fundamental importance for patients undergoing implant-related surgery to enable the provision of valid informed consent.
CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME
Authors: Sallee Colin J. , Maddux Aline B. , Hippensteel Joseph A. , Markovic Daniela , Oshima Kaori , Schwingshackl Andreas , Mourani Peter M. , Schmidt Eric P. , Sapru Anil
Published: September 2024

Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018–2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.
A Qualitative Exploration of Women With Cystic Fibrosis and Urinary Incontinence
Authors: Vargas Laura , Kazmerski Traci M. , von Berg Karen , Patterson Danielle , West Natalie , Bradley Megan
Published: September 2024

Importance

Women with cystic fibrosis (CF) historically experience a high prevalence of urinary incontinence (UI). However, this area is understudied, especially in the modern era of highly effective modulator therapy (HEMT).

Objective

This study aimed to explore the UI experiences, knowledge, care-seeking behavior, and treatment preferences of women with CF.

Study Design

We recruited women aged ≥18 years through the CF Foundation's Community Voice national registry if they had a diagnosis of CF and reported UI. Participants underwent individual, semistructured interviews exploring their experiences, attitudes, and preferences toward UI that were audiorecorded and transcribed. Two coders performed thematic analysis using deductive and inductive coding approaches.

Results

Twenty-six participants completed interviews (average age, 45.1 years; range, 24–61 years). Key themes included the following: (1) most women with CF and UI report low bother from symptoms likely related to stress UI, and HEMT has greatly improved UI symptoms and decreased bother; (2) most women with CF and UI had previously discussed UI symptoms with family and/or peers but had not sought care due to stigma or low priority; (3) women with CF and UI had minimal knowledge about UI in general and how it relates to CF; (4) most desired broad screening for UI from their CF team and improved multidisciplinary care; and (5) highly effective UI treatment options with low-time commitment and easily accessible resources are desired.

Conclusions

Women with CF and UI report low knowledge and care-seeking behavior related to this condition and desire improved care provision. Importantly, HEMT may improve UI symptoms among people with CF.
Impact of Age on Perioperative Complications After Obliterative Vaginal Surgery
Authors: Mowers Erin E. , Vargas Laura G. , Shepherd Jonathan P. , Bonidie Michael J. , Ackenbom Mary F.
Published: September 2024

Importance

Obliterative vaginal surgery is often reserved for older patients with prolapse, but the effect of age as an independent risk factor for perioperative complications in this cohort is poorly understood.

Objective

The aim of this study was to assess the association between age and perioperative complications in women undergoing obliterative vaginal surgery.

Study Design

This was a retrospective cohort study that included 371 patients undergoing colpocleisis between 2010 and 2013 at a single academic medical center. Seventy demographic and clinical variables, including complications within 12 weeks of surgery, were analyzed. The χ2 and Fisher exact tests were used for categorical variables. Student t and Mann-Whitney U tests were used for continuous variables. Univariate logistic regression was performed to identify predictors of perioperative complications, and candidate variables with P < 0.2 were used in multivariate logistic regression.

Results

The mean patient age was 75.4 ± 6.4 years (range, 59–94 years). One hundred ten (29.7%) patients experienced at least 1 complication, the most common of which was urinary tract infection (n = 47, 12.7%). In the final multivariable model, only age (odds ratio, 1.05 per year; 95% confidence interval, 1.01–1.08) remained a significant predictor of perioperative complications. A cut point of age ≥70.5 years maximized sensitivity and specificity for predicting complications.

Conclusions

Among women undergoing obliterative vaginal surgery, age is a predictor of perioperative complications. Each increasing year of age increases the complication likelihood by 1.05-fold, such that an 85-year-old woman is 1.05^20 or 2.65 times more likely than a 65-year-old woman to have a complication. A cut point of ≥70.5 years best predicted complications. Despite this association, severe perioperative complications following obliterative surgery are rare.
The maternal and perinatal health data system in the Kilimanjaro Region, Tanzania: a landscape review including a qualitative study
Authors: Mitao Modesta , Pima Francis M. , Munishi Lucy , Cronin Mary , Olomi Gaudensia A. , Lyimo Allen , Senkoro Allen , Nkya Gustarv , Somi Jackline , Buckely Daire , Kyara Yudathadeus , Shuma Anne , Rashid Fatina , Mchome Bariki , Mahande Michael Johnson , Khanga Jairy , Hirst Jane , Redman Christopher , Woodworth Simon , Mmbaga Blandina T. , Khashan Ali S
Published: September 2024

Background The World Health Organization (WHO) advocates the use of digital health interventions to strengthen health systems globally. This landscape review evaluated how data related to maternal and neonatal health is recorded and utilized for clinical and policy decision-making in the Kilimanjaro Region of Tanzania. Method This landscape review employed a dual method approach, initially quantifying data recording practices of each clinic and then using qualitative interviews to explore how data is currently captured and utilized. We conducted interviewed with seven Nurse-Midwives, eight Lead Obstetricians at district hospitals, seven District Medical Officers, and seven District Reproductive and Child Health Coordinators. Qualitative data analysis was performed using NVivo software. Results In the region's seven districts, there are 489 healthcare facilities offering Reproductive and Child Health Services, delivery, infant and child care. The facilities comprise 22 hospitals, 62 health centers, 353 dispensaries, and 52 clinics. In 2021, there were 45,343 births with a maternal mortality rate of 146 per 100,000 live births, a neonatal mortality rate of 10.1 per 1,000 live births, and a stillbirth rate of 4 per 1,000 births. Additionally, 20.3% of births were delivered via C-section. Although there was a notable decline in maternal and neonatal mortality rates (from 112 to 51 vs 9.5 to 3.7 deaths per 100,000 live births) from 2020 to 2023, the 2021 data revealed unexpectedly high maternal mortality rates. The qualitative study highlighted issues with the data recording system, which is complex and time-consuming, involving multiple paper-based and digital records. Challenges include data volume, loss, and retrieval issues, affecting clinical decision-making. This data is crucial for identifying resource needs, monitoring health trends like low antenatal care uptake, and advocating for changes in resources, guidelines, and policies at regional and national levels. Conclusion Quantitative data indicates a significant rise in maternal and neonatal mortality rates in the Kilimanjaro region during 2020-2021, followed by a decrease in 2022-2023. Additionally, early antenatal care (ANC) uptake remains below 50%. The qualitative study suggests that paper records are time-consuming and prone to incomplete data making it difficult to use due to their storage approach and the risk of damage to the physical books.
Generalizable Morphological Profiling of Cells by Interpretable Unsupervised Learning
Authors: Murthy Rashmi Sreeramachandra , Stassen Shobana V. , Siu Dickson M. D. , Lo Michelle C. K. , Yip Gwinky G. K. , Tsia Kevin K.
Published: September 2024

The intersection of advanced microscopy and machine learning is revolutionizing cell biology into a quantitative, data-driven science. While traditional morphological profiling of cells relies on labor-intensive manual feature extraction susceptible to biases, deep learning offers promising alternatives but struggles with the interpretability of its black-box operation and dependency on extensive labeled data. We introduce MorphoGenie, an unsupervised deep-learning framework designed to address these challenges in single-cell morphological profiling. Enabling disentangled representation learning integrated with high-fidelity image reconstructions, MorphoGenie possesses a critical attribute to learn a compact, generalizable and interpretable latent space. This facilitates the extraction of biologically meaningful features without human annotation, additionally overcoming the "curse of dimensionality" inherent in manual methods. Unlike prior models, MorphoGenie introduces a systematic approach to mapping disentangled latent representations to fundamental hierarchical morphological attributes, ensuring both semantic and biological interpretability. Moreover, it adheres to the concept of combinatorial generalization—a core principle of human intelligence— which greatly enhances the model’s capacity to generalize across a broad spectrum of imaging modalities (e.g., quantitative phase imaging and fluorescence imaging) and experimental conditions (ranging from discrete cell type/state classification to continuous trajectory inference). The framework offers a new, generalized strategy for unbiased and comprehensive morphological profiling, potentially revealing insights into cellular behavior in health and disease that might be overlooked by expert visual examination.
The p97-UBXD8 complex maintains peroxisome abundance by suppressing pexophagy
Authors: Montes Iris D. , Amirthagunanathan Suganthan , Joshi Amit S. , Raman Malavika
Published: September 2024

Peroxisomes are vital organelles involved in key metabolic functions in eukaryotic cells. Their significance is highlighted by peroxisome biogenesis disorders; severe childhood diseases marked by disrupted lipid metabolism. One mechanism regulating peroxisome abundance is through selective ubiquitylation of peroxisomal membrane proteins that triggers peroxisome degradation via selective autophagy (pexophagy). However, the mechanisms regulating pexophagy remain poorly understood in mammalian cells. Here we show that the evolutionarily conserved AAA-ATPase p97 and its membrane embedded adaptor UBXD8 are essential for maintaining peroxisome abundance. From quantitative proteomic studies we reveal that loss of UBXD8 affects many peroxisomal proteins. We find depletion of UBXD8 results in a loss of peroxisomes in a manner that is independent of the known role of UBXD8 in ER associated degradation (ERAD). Loss of UBXD8 or inhibition of p97 increases peroxisomal turnover through autophagy and can be rescued by depleting key autophagy proteins or overexpressing the deubiquitylating enzyme USP30. Furthermore, we find increased ubiquitylation of the peroxisomal membrane protein PMP70 in cells lacking UBXD8 or p97. Collectively, our findings identify a new role for the p97-UBXD8 complex in regulating peroxisome abundance by suppressing pexophagy.
Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages (LAMs)
Authors: Xu Yingzheng , Hillman Hannah , Chang Michael , Ivanov Stoyan , Williams Jesse W.
Published: September 2024

Macrophages are essential immune cells present in all tissues, and are vital for maintaining tissue homeostasis, immune surveillance, and immune responses. Considerable efforts have identified shared and tissue-specific gene programs for macrophages across organs during homeostasis. This information has dramatically enhanced our understanding of tissue-restricted macrophage programming and function. However, few studies have addressed the overlapping and tissue-specific responses of macrophage subsets following inflammatory responses. One subset of macrophages that has been observed across several studies, lipid-associated macrophages (LAMs), have gained interest due to their unique role in lipid metabolism and potential as a therapeutic target. LAMs have been associated with regulating disease outcomes in metabolically related disorders including atherosclerosis, obesity, and nonalcoholic fatty liver disease (NAFLD). In this study, we utilized single-cell RNA sequencing (scRNAseq) data to profile LAMs across multiple tissues and sterile inflammatory conditions in mice and humans. Integration of data from various disease models revealed that LAMs share a set of conserved transcriptional profiles, includingTrem2andLpl, but also identified key sets of tissue-specific LAM gene programs. Importantly, the shared LAM markers were highly conserved with human LAM populations that also emerge in chronic inflammatory settings. Overall, this analysis provides a detailed transcriptional landscape of tissue-restricted and shared LAM gene programs and offers insights into their roles in metabolic and chronic inflammatory diseases. These data may help instruct appropriate targets for broad or tissue-restricted therapeutic interventions to modulate LAM populations in disease.
A Global Assessment of Plant-Mite Mutualism and its Ecological Drivers
Authors: Myers Andrew , Martin Bruce , Yonenaga Jenna , Agrawal Anurag A. , Weber Marjorie G.
Published: September 2024

Mutualisms are mediated by adaptive traits of interacting organisms and play a central role in the ecology and evolution of species. Thousands of plant species possess tiny structures called “domatia” that house mites which protect plants from pests, yet these traits remain woefully understudied. Here we release a worldwide database of species with mite domatia and provide the first evaluation of the phylogenetic and geographic distribution of this mutualistic trait. With >2,500 additions based on digital herbarium scans and published reports, we increased the number of known species with domatia by 27% and, importantly, documented their absence in >4,000 species. We show that mite domatia likely evolved hundreds of times among flowering plants, occurring in an estimated ∼10% of woody species representing over a quarter of all angiosperm families. Contrary to classic hypotheses about the evolutionary drivers of mutualism, we find that mite domatia evolved more frequently in temperate regions and in deciduous lineages; this pattern is concordant with a large-scale geographic transition from predominantly ant-based plant defense mutualisms in the tropics to mite-based defense mutualisms in temperate climates. Our data also reveal a previously undescribed pattern of evolutionary convergence in domatia morphology, with tuft-form domatia more likely to evolve in dry temperate habitats and pit domatia were more likely to evolve in wet tropical environments. We have shown climate-associated drivers of mite domatia evolution, demonstrating their utility and power as an evolutionarily replicated system for the study of plant defense mutualisms.
Unveiling allopolyploidization-driven genome duplications through progressive analysis of deep genome skimming data
Authors: Xie Si-Yu , Lin Xiao-Hua , Wang Jun-Ru , Ma Dai-Kun , Zhang Yu , Xu Chao , Ma Hong , Li Pan , Chen Duo-Yuan , Zhong Xin , Ge Bin-Jie , Hodel Richard G.J. , Zhao Liang , Liu Bin-Bin
Published: September 2024

Whole-genome duplication (WGD) events are widespread across the Web of Life (WoL). Given the prevalence of WGDs in the polyploidPrunus(Rosaceae), this economically- and agriculturally-important angiosperm lineage provides an excellent model for exploring this mode of reticulation. We used the polyploidPrunusto demonstrate a progressive strategy for analyzing Deep Genome Skimming (DGS) data in the presence of WGDs. Phylogenomic discordance analyses indicated that allopolyploidization, rather than Incomplete Lineage Sorting (ILS), played a dominant role in the origin and dynamics of polyploidPrunus. This study underscores how a progressive strategy to identify WGD events at different depths in a phylogenetic tree reveals the nuances of evolutionary mechanisms driving allopolyploidization. We inferred that the continued uplift of the Himalayas from the Middle to Late Miocene drove the rapid diversification of the Eastern Asia endemicMaddeniaclade, by facilitating frequent hybridization and allopolyploidization, specifically introgression between the Himalayas-Hengduan and the Central-Eastern China clades.
Rfx3 controls outer hair cell differentiation, maintenance, and hair bundle formation by regulating the expression ofInsm1, Ikzf2, andTriobpgenes
Authors: Zhang Penghui , Wang Yafan , Guo Xiang , Ma Lu , Zeng Xiangyao , Feng Zhili , Liu Jinlei , Yan Mengzhen , Gao Yushan , Dong Jieran , Li Junhong , Ling Jie , Wu Hong , Jing Qianchen , Feng Yong , Li Jun
Published: September 2024

The RFX family of transcription factors plays crucial roles in the regulation of ciliogenesis and organ development. Mutations of RFX transcription factors lead to various genetic diseases, including ciliopathies and hearing loss, although the underlying mechanisms remain unclear. This study comprehensively analyzed the expression patterns of RFX family members during different inner ear developmental stages. Rfx3 and Rfx7 were identified as the dominantly expressed members in cochlear hair cells, exhibiting alternative splicing variants and dynamic subcellular localization at different stages. Integration of single-cell transcriptomics, ChIP-seq, and ATAC-seq data indicates that Rfx3 functions as either a transcriptional activator or repressor, binding to numerous genes related to ciliogenesis, hair bundle structures, and planar cell polarity. Rfx3 regulates the spatiotemporal expression of hair bundle geneTriobpin hair cells by binding to and modulating its intronic enhancer. Additionally, Rfx3 binds to hair cell differentiation and fate determination genesTbx2,Insm1, andIkzf2. The results demonstrate that Rfx3 and Rfx7 are dominantly expressed in outer hair cells, with their subcellular localization shifting to cytoplasm at later developmental stages. This suggests a previously unknown function of Rfx3 and Rfx7 beyond transcriptional regulation, highlighting their complex roles in hair cell differentiation and maintenance.