bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of mitral valve disease etiology on the outcomes of mechanical and biological valve replacement: retrospective cohort study
Authors: Chen Chun-Yu , Chang Feng-Cheng , Lin Chia-Pin , Chan Yi-Hsin , Wu Victor Chien-Chia , Cheng Yu-Ting , Chu Pao-Hsien , Chou An-Hsun , Yeh Chi-Hsiao , Chen Shao-Wei
Published: March 2024

Introduction:

The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival.

Methods:

Using data (2002–2018) from Taiwan’s National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation.

Results:

In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation.

Conclusion:

The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.
Outcome variation and the role of caseload in certified colorectal cancer centers – a retrospective cohort analysis of 90 000 cases
Authors: Hunger Richard , Kowalski Christoph , Paasch Christoph , Kirbach Jette , Mantke René
Published: March 2024

Background:

Studies have shown that surgical treatment of colorectal carcinomas in certified centers leads to improved outcomes. However, there were considerable fluctuations in outcome parameters. It has not yet been examined whether this variability is due to continuous differences between hospitals or variability within a hospital over time.

Materials and Methods:

In this retrospective observational cohort study, administrative quality assurance data of 153 German-certified colorectal cancer centers between 2010 and 2019 were analyzed. Six outcome quality indicators (QIs) were studied: 30-day postoperative mortality (POM) rate, surgical site infection (SSI) rate, anastomotic insufficiency (AI) rate, and revision surgery (RS) rate. AI and RS were also analyzed for colon (C) and rectal cancer operations (R). Variability was analyzed by funnel plots with 95% and 99% control limits and modified Cleveland dot plots.

Results:

In the 153 centers, 90 082 patients with colon cancer and 47 623 patients with rectal cancer were treated. Average QI scores were 2.7% POM, 6.2% SSI, 4.8% AI-C, 8.5% AI-R, 9.1% RS-C, and 9.8% RS-R. The funnel plots revealed that for every QI, about 10.1% of hospitals lay above the upper 99% and about 8.7% below the lower 99% control limit. In POM, SSI, and AI-R, a significant negative correlation with the average annual caseload was observed.

Conclusion:

The analysis showed high variability in outcome quality between and within the certified colorectal cancer centers. Only a small number of hospitals had a high performance on all six QIs, suggesting that significant quality variation exists even within the group of certified centers.
RARPKB: a knowledge-guide decision support platform for personalized robot-assisted surgery in prostate cancer
Authors: Li Jiakun , Tang Tong , Wu Erman , Zhao Jing , Zong Hui , Wu Rongrong , Feng Weizhe , Zhang Ke , Wang Dongyue , Qin Yawen , Shen Zheng , Qin Yi , Ren Shumin , Zhan Chaoying , Yang Lu , Wei Qiang , Shen Bairong
Published: March 2024

Background:

Robot-assisted radical prostatectomy (RARP) has emerged as a pivotal surgical intervention for the treatment of prostate cancer (PCa). However, the complexity of clinical cases, heterogeneity of PCa, and limitations in physician expertise pose challenges to rational decision-making in RARP. To address these challenges, the authors aimed to organize the knowledge of previously complex cohorts and establish an online platform named the RARP knowledge base (RARPKB) to provide reference evidence for personalized treatment plans.

Materials and methods:

PubMed searches over the past two decades were conducted to identify publications describing RARP. The authors collected, classified, and structured surgical details, patient information, surgical data, and various statistical results from the literature. A knowledge-guided decision-support tool was established using MySQL, DataTable, ECharts, and JavaScript. ChatGPT-4 and two assessment scales were used to validate and compare the platform.

Results:

The platform comprised 583 studies, 1589 cohorts, 1 911 968 patients, and 11 986 records, resulting in 54 834 data entries. The knowledge-guided decision support tool provide personalized surgical plan recommendations and potential complications on the basis of patients’ baseline and surgical information. Compared with ChatGPT-4, RARPKB outperformed in authenticity (100% vs. 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), matching of patients (100% vs. 0%), and personalized recommendations for complications (100% vs. 20%). Postuse, the average System Usability Scale score was 88.88±15.03, and the Net Promoter Score of RARPKB was 85. The knowledge base is available at: http://rarpkb.bioinf.org.cn.

Conclusions:

The authors introduced the pioneering RARPKB, the first knowledge base for robot-assisted surgery, with an emphasis on PCa. RARPKB can assist in personalized and complex surgical planning for PCa to improve its efficacy. RARPKB provides a reference for the future applications of artificial intelligence in clinical practice.
Construction of S100 family members prognosis prediction model and analysis of immune microenvironment landscape at single-cell level in pancreatic adenocarcinoma: a tumor marker prognostic study
Authors: Xu Zi-jin , Li Jian-ang , Cao Ze-yuan , Xu Hua-xiang , Ying Ying , Xu Zhi-hang , Liu Run-jie , Guo Yuquan , Zhang Zi-xin , Wang Wen-quan , Liu Liang
Published: March 2024

Pancreatic adenocarcinoma characterized by a mere 10% 5-year survival rate, poses a formidable challenge due to its specific anatomical location, making tumor tissue acquisition difficult. This limitation underscores the critical need for novel biomarkers to stratify this patient population. Accordingly, this study aimed to construct a prognosis prediction model centered on S100 family members. Leveraging six S100 genes and their corresponding coefficients, an S100 score was calculated to predict survival outcomes. The present study provided comprehensive internal and external validation along with power evaluation results, substantiating the efficacy of the proposed model. Additionally, the study explored the S100-driven potential mechanisms underlying malignant progression. By comparing immune cell infiltration proportions in distinct patient groups with varying prognoses, the research identified differences driven by S100 expression. Furthermore, the analysis explored significant ligand-receptor pairs between malignant cells and immune cells influenced by S100 genes, uncovering crucial insights. Notably, the study identified a novel biomarker capable of predicting the sensitivity of neoadjuvant chemotherapy, offering promising avenues for further research and clinical application.
Multiparametric MRI subregion radiomics for preoperative assessment of high-risk subregions in microsatellite instability of rectal cancer patients: a multicenter study
Authors: Cai Zhiping , Xu Zhenyu , Chen Yifan , Zhang Rong , Guo Baoliang , Chen Haixiong , Ouyang Fusheng , Chen Xinjie , Chen Xiaobo , Liu Dechao , Luo Chun , Li Xiaohong , Liu Wei , Zhou Cuiru , Guan Xinqun , Liu Ziwei , Zhao Hai , Hu Qiugen
Published: March 2024

Background:

Microsatellite instability (MSI) is associated with treatment response and prognosis in patients with rectal cancer (RC). However, intratumoral heterogeneity limits MSI testing in patients with RC. The authors developed a subregion radiomics model based on multiparametric MRI to preoperatively assess high-risk subregions with MSI and predict the MSI status of patients with RC.

Methods:

This retrospective study included 475 patients (training cohort, 382; external test cohort, 93) with RC from two participating hospitals between April 2017 and June 2023. In the training cohort, subregion radiomic features were extracted from multiparametric MRI, which included T2-weighted, T1-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. MSI-related subregion radiomic features, classical radiomic features, and clinicoradiological variables were gathered to build five predictive models using logistic regression. Kaplan–Meier survival analysis was conducted to explore the prognostic information.

Results:

Among the 475 patients [median age, 64 years (interquartile range, IQR: 55–70 years); 304 men and 171 women], the prevalence of MSI was 11.16% (53/475). The subregion radiomics model outperformed the classical radiomics and clinicoradiological models in both training [area under the curve (AUC)=0.86, 0.72, and 0.59, respectively] and external test cohorts (AUC=0.83, 0.73, and 0.62, respectively). The subregion-clinicoradiological model combining clinicoradiological variables and subregion radiomic features performed the optimal, with AUCs of 0.87 and 0.85 in the training and external test cohorts, respectively. The 3-year disease-free survival rate of MSI groups predicted based on the model was higher than that of the predicted microsatellite stability groups in both patient cohorts (training, P=0.032; external test, P=0.046).

Conclusions:

The authors developed and validated a model based on subregion radiomic features of multiparametric MRI to evaluate high-risk subregions with MSI and predict the MSI status of RC preoperatively, which may assist in individualized treatment decisions and positioning for biopsy.
Patient-Centered Innovation
Authors: Jung Olivia S. , Kyle Michael Anne , McCree Paula , Nadel Hiyam M.
Published: March 2024

Background:

Involving patients in the health-care delivery innovation has many benefits. Open social innovation (OSI) presents a fitting lens to examine and advance patient engagement in innovation. OSI offers a participatory approach to innovation, in which diverse groups of participants collaboratively generate ideas and scale solutions on complex social challenges.

Purpose:

This study: (1) describes a pilot application of OSI, in which individuals serving on a hospital’s patients and family advisory councils (PFACs) were invited to participate in an innovation contest; and (2) explores the extent to which patients’ beliefs about their role in innovation relate to their participation in the contest.

Methodology/Approach:

We conducted an innovation contest that invited PFAC members to share ideas that would improve patient experiences and then vote on and select the ideas that they wanted to see move forward. We measured patients’ beliefs about their role in innovation in a survey before the contest.

Results:

Twenty individuals submitted 27 ideas. Patients who expressed preference for more involvement in innovation were more likely to participate.

Conclusions:

Using OSI may help expand patient engagement in innovation, particularly among those who want to be more involved but do not feel authorized to voice ideas in traditional advisory committees.

Practical Implications:

OSI spurred collaboration among patients, clinicians, quality improvement staff, hospital administrators, and other stakeholders in idea generation, elaboration, and implementation. More experimentation and research are needed to understand how OSI can be leveraged to capture patients’ voice and incorporate them in care delivery innovation.
Angiodysplasia simulating variceal bleeding: a challenging case report of diagnosis and intervention
Authors: Chataut Dinesh , Katwal Shailendra , Suwal Sundar , Thapa Ajit , Bhattarai Bharosha
Published: March 2024

Introduction and importance:

Angiodysplasia, a prevalent vascular anomaly in the gastrointestinal tract, often presents with upper gastrointestinal bleeding, sharing symptoms with gastric varices. The diagnostic challenge arises due to overlapping clinical features. This case report highlights the importance of considering angiodysplasia in the differential diagnosis, especially when variceal bleeding is less likely, and emphasizes the role of various diagnostic modalities in accurate identification.

Case presentation:

A 52-year-old male presented with severe hematemesis and melena, mimicking variceal bleeding. Despite initial management, bleeding persisted. Contrast-enhanced computed tomography revealed dilated vascular channels, raising suspicion for both gastric varices and angiodysplasia. Endoscopy confirmed an angiomatous lesion, inadvertently disrupted during the procedure, necessitating angiography. The angiographic findings supported the diagnosis of angiodysplasia, and successful interventions included temporary glue embolization and argon laser coagulation during endoscopy. The patient was discharged with stable hemoglobin; a 2-year follow-up showed no recurrence.

Clinical discussion:

The case discusses the challenges in differentiating angiodysplasia from varices, emphasizing the role of imaging and endoscopic modalities. It highlights the need for a tailored approach to treatment, including argon plasma coagulation, and underscores the significance of meticulous follow-up for recurrence.

Conclusion:

This case report elucidates the diagnostic and therapeutic journey in managing a patient with angiodysplasia masquerading as variceal bleeding. It emphasizes the importance of considering vascular anomalies without typical signs and the significance of individualized interventions for optimal patient outcomes. The 2-year follow-up without recurrence signifies the successful management of the case.
Fear of falling, quality of life, and daily functional activity of elderly women with and without a history of falling: a cross-sectional study
Authors: Miri Sahar , Norasteh Ali Asghar
Published: March 2024

Background:

This study aimed to evaluate the fear of falling, quality of life, and daily functional activity of older women aged 60 years or older with or without a history of falling.

Materials and methods:

Two hundred older adult women were recruited for the cross-sectional study in Iran. This cross-sectional study collected data from July to August 2023 through convenience sampling. The researchers collected data using a five-part questionnaire, that collected information that included demographic characteristics, the Fall Efficacy Scale in the Elderly-International Version (FES-I), 12-item Quality of Life assessment (SF-12), Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL).

Results:

FES-I score in older women with a history of falls was significantly higher than those without a history of falls [median: 38.0, interquartile range (IQR): 31.5–44.0 versus median: 22.0, IQR: 20.0–30.0; P<0.001]. The median quality-of-life score using the SF-12 was significantly lower in women with a history of falls than in those without a history of falls (median: 25.0, IQR: 21.0–30.0 versus median: 35.0, IQR: 31.0–39.0; P<0.001). The ADL scores were significantly lower among women with a history of falls than those without (P<0.001). A similar result was obtained for IADL scores (P<0.001).

Conclusion:

Overall, this study’s findings highlight the adverse impact of a history of falls on three key factors: fear of falling, quality of life, and daily functional activity (including both basic and instrumental activities). The findings delineate that, ultimately, the history of falls can serve as a valuable indicator for better understanding trends in elderly care and addressing the associated challenges.
Unilateral lateral rectus palsy following dengue: a case report
Authors: Niraula Biraj , Adhikari Bindira , Suvedi Anil , Gosain Dinesh , Gaud Shivendra Kumar
Published: March 2024

Introduction and importance:

Dengue fever is a mosquito-borne viral infection presenting with high-grade fever and other constitutional symptoms.

Case presentation:

This case report details a rare occurrence of lateral rectus palsy in an 18-year-old male subsequent to dengue infection. The patient initially presented with fever, a generalized tonic-clonic seizure (GTCS), and symptomatic hypoglycemia, leading to multiple organ dysfunction syndrome (MODS) necessitating intensive care. Remarkably, no haemorrhagic manifestations were observed. The MODS gradually resolved by the 12th day of admission, coinciding with the emergence of complaints about uniocular diplopia and right esotropia. Systemic examination, including a normal computed tomography (CT) head scan, did not reveal any abnormalities. Additionally, potential causes contributing to esotropia and diplopia were ruled out. The patient was subsequently managed expectantly for lateral rectus palsy following severe dengue. Follow-up assessments indicated a gradual improvement in esotropia and diplopia, and the patient was advised to continue the prescribed medications.

Conclusion:

This is the first documented case report of paralytic squint post-severe dengue in Nepal, emphasizing the importance of considering it as a differential diagnosis in tropical regions with endemic dengue infections. The case report advocates early identification and treatment of ophthalmic issues, notably with prednisolone, to achieve favourable outcomes, as evidenced by improvements in visual acuity, esotropia, and diplopia during follow-ups. Further research is essential to determine optimal treatment strategies for such neurological complications associated with dengue fever.
What Are the Perceptions of Recipients of Allogeneic Hematopoietic Stem Cell Transplant About Medication Adherence?
Authors: Visintini Chiara , Mansutti Irene , Palese Alvisa
Published: March 2024

Background

Recipients of allogeneic hematopoietic stem cell transplant (HSCT) may encounter difficulties in adhering to their post-transplant medication as prescribed to avoid complications. Despite the relevance of patients’ perspectives to inform the clinical practice, to date, no summary regarding their lived experience of oral medication adherence (MA) has been produced.

Objective

To summarize the lived experience of MA by recipients of allogeneic HSCT as documented in qualitative studies.

Methods

A systematic review and meta-synthesis of qualitative research was performed. Six databases were searched up to June 27, 2023. Four qualitative studies met eligibility and were included: those designed and conducted with scientifically sound methodologies and those regarding adult patients who had undergone allogeneic HSCT and required an oral medication regimen in the post-transplant phase. Data were extracted and synthesized using thematic analysis.

Results

Four analytical themes were identified: “The initiation is a challenge,” “Time as a new issue,” “Internal and external obstacles threaten medication adherence,” and “Different strategies are the answer to medication non-adherence.”

Conclusions

Medication adherence in patients after HSCT is a complex phenomenon wherein different factors play a role. When designing targeted interventions to improve MA, it is imperative to start with patients’ experiences and perspectives.

Implications for Practice

Patients developed different strategies to deal with obstacles to MA that may inform daily practice. Before discharge, healthcare professionals should emphasize to both patients and carers the importance of MA.
Social Determinants of Health and Satisfaction With Sources of Information About COVID-19 Related to Vaccine Uptake in a Safety Net Health Care System
Authors: Blake Nancy , Siddiq Hafifa , Brecht Mary-Lynn , Warda Umme , Villacorte Ferlie , Banawa John
Published: March 2024

Background

Vaccination is a critical tool to combat the COVID-19 pandemic. Yet, vaccine uptake varies across communities and is often affected by sociodemographic factors and accessibility.

Objectives

This paper outlines a pilot study aimed to examine factors associated with COVID-19 patients within one of the nation’s largest safety net health care systems.

Methods

A cross-sectional survey design was conducted with adults over 18 eligible to receive the COVID-19 vaccine. Descriptive analysis of survey data collected in 2021–2022 was employed. Unconditional and multivariate logistic regression analyses were conducted to examine associations between sociodemographics, social factors, and COVID-19 vaccine uptake.

Results

Study participants (N = 280) were a diverse patient population, primarily low-income and majority Hispanic/Latinx, with low education levels but with a high level of COVID-19 vaccine uptake and a high rate of intent to vaccinate again. Approximately 22% report having unstable housing, and 46% experiencing food insecurity. Most trusted sources for COVID-19 data included mainstream media, including TV, radio and newspapers and friends, family, or other informal networks. We found that respondents who were satisfied or very satisfied with COVID-19 information received from health care providers or the government had higher odds of vaccine uptake rates.

Discussion

These findings highlight the critical role of access to the COVID-19 vaccine and sources of information as an independent factor in COVID-19 vaccine uptake among patients within a safety net health care system. This study expands the literature on COVID-19 vaccine uptake, particularly in an under-resourced region of the South Los Angeles community. Future research is needed to better understand the mechanisms between social determinants of health, perceived discrimination, and vaccine uptake.
The Genetic Approach to Stillbirth: A Systematic Review
Authors: Merc Maja Dolanc , Peterlin Borut , Lovrecic Luca
Published: March 2024

Stillbirth represents a significant burden to individuals and families and has a great variety of causes, but much is still unknown about the underlying etiologies. The overall contribution of genetic abnormalities to stillbirth is not well known; this study was designed to evaluate known genetic causes of unexplained stillbirths, as well as understand the current position and future direction for using genetic and genomic testing in this field.

This study was a systematic review of literature published between 1953 and 2020 on genetic testing and stillbirth. Inclusion criteria for studies were human cases, details and specific data on cohorts that included proportion of unexplained fetal deaths, and data on genetic testing and the subsequent results. Exclusion criteria were pregnancy loss before 22 weeks of gestation, focus on known causes of stillbirth, focus on fetal pathology or abnormalities, investigating neonatal death, genetic testing in populations with congenital anomalies or suspected specific syndromes, and those without details on genetic testing. The final review included 9 studies, 1 comparing karyotyping and chromosomal microarray analysis (CMA); 1 comparing karyotyping, CMA, and quantitative fluorescence–polymerase chain reaction; 2 with CMA only; and 5 with exome sequencing data.

The studies that examined only CMA found 1 case of copy number variants (CNVs) in 24 cases and 31 CNVs in 96 cases. The largest study included here analyzed 532 stillbirths and compared CMA and karyotyping. Chromosomal microarray analysis showed a higher rate of detection of CNVs, increasing from 5.8% to 8.3% (P = 0.007) when compared with karyotype analysis.

One challenge presented by this topic is that some disorders that could contribute to unexplained stillbirth are typically diagnosed when symptoms appear later in life and so are not usually associated with stillbirth or the risk of stillbirth. One example of this could be cardiac rhythm anomalies or other rare genetic variants that lead to stillbirth when appearing in a particular variation. One study included a cohort of unexplained stillbirth after postmortem examination that excluded obvious causes. Genetic analysis showed that several cases carried a variant that was functionally disruptive that may have contributed to stillbirth, but several additional cases that were functionally normal.

Genetic variations relating to unexplained stillbirth are a broad and largely unexplored topic. Genetics play a vital role in clinical exploration and treatment of many disorders and in diagnosing causes of fetal mortality and morbidity. This review shows that genetic testing for stillbirth varies greatly according to test availability and guidelines of use, with some tests showing greater diagnostic yield than others. Although these studies incorporated large cohorts of unexplained stillbirths, genetic analysis identified potential causes for only a small percentage. Future research is needed to explain potential genetic causes for stillbirth.
Fatal Vertebral Artery Dissection Following Self-Manipulation of the Cervical Spine
Authors: Persons Jane E. , Stauffer Stephanie
Published: March 2024

Cervical spine manipulation is a known risk factor for vertebral artery dissection. In this report, we present a case of fatal vertebral artery dissection that occurred as the result of self-manipulation of the cervical spine. The decedent was a 40-year-old man with no significant past medical history. He was observed to “crack his neck” while at work. Soon after, he began experiencing neck pain, then developed strokelike symptoms and became unresponsive. He was transported to a local medical center, where imaging showed bilateral vertebral artery dissection. His neurological status continued to decline, and brain death was pronounced several days later. An autopsy examination showed evidence of cerebellar and brainstem infarcts, herniation, and diffuse hypoxic-ischemic injury. A posterior neck dissection was performed to expose the vertebral arteries, which showed grossly visible hemorrhage and dilation. There was no evidence of traumatic injury to the bone or soft tissue of the head or neck. Bilateral dissection tracts were readily appreciated on microscopic examination. Death was attributed to self-manipulation of the neck, which in turn led to bilateral vertebral artery dissection, cerebellar and brainstem infarcts, herniation, hypoxic-ischemic injury, and ultimately brain death.
The Barriers to Recognizing and Reporting Child Physical Abuse by Emergency Physicians and Associated Factors
Authors: Lee Dongwoo , Lee Jin Hee , Kwak Young Ho , Suh Dongbum , Kwon Hyuksool , Kim Do Kyun , Jung Jin Hee , Park Joong Wan , Lee Ha Ni , Kim Jin Hee
Published: March 2024

Background

Although the reporting rate of child abuse is increasing every year, the child abuse detection rate is 3.81% as of 2019 in Korea, which is significantly lower than that of developed countries for child rights.

Objective

We investigated the associated factors with barriers that emergency physicians face in recognizing and reporting cases of child abuse.

Methods

From May to July 2022, 240 emergency physicians working in the 15 emergency department were asked to participate in the survey via email. The questionnaire included the respondent's basic information, treatment experience for child abuse, reasons for reporting or not reporting, and opinions on measures to increase the reporting rate. We conducted a logistic regression analysis to discern the factors contributing to underreporting.

Results

Seventy-one individuals were included in the analysis, after excluding those who had never encountered suspected cases of child abuse. A multivariable logistic regression was performed with the above variables, and although it was not statistically significant, there was a tendency for workers to report well when working at a pediatric emergency department (odds ratio [95% confidence interval], 3.97 [0.98–16.09]). The primary reason for reporting suspected abuse was the pattern of damage suspected of abuse. The first reason for not reporting suspected abuse was because they were not sure it was child abuse. Respondents answered that to report better, a quick and appropriate response from the police and confidentiality of the reporter were needed.

Conclusions

Physicians in pediatric emergency departments demonstrated a tendency for more proactive reporting suspected cases of child abuse.
Efficacy and Safety of 225Ac-DOTATATE in the Treatment of Neuroendocrine Neoplasms With High SSTR Expression
Authors: Yang Hongyu , Zhang Yu , Li Hongmei , Zhang Yu , Feng Yue , Yang Xiqun , Chen Yue
Published: March 2024

Purpose

We aimed to evaluate the efficacy and safety of 225Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression.

Patients and Methods

This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68Ga-DOTATATE PET/CT imaging. All patients received 225Ac-DOTATATE TAT. The primary end points were molecular imaging–based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0).

Results

A molecular imaging–based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7–22 months), and no deaths were reported.

Conclusions

This initial study suggests that 225Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.
Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty
Authors: Dou Jinfeng , Huang Yixuan , Cheng Xu , Li Jingtao , Shi Bing
Published: March 2024

This study aimed to introduce a surgery technique—Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon’s experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.
Online Search Strategies and Results From a Crowdsourced Survey on Asymptomatic Bacteriuria
Authors: Bradley Megan S. , Hetzel-Riggin Melanie D. , Knight Julia C. , Murillo Ashley , Zyczynski Halina , Shelton Christopher R.
Published: March 2024

Importance

Despite the prevalence of asymptomatic bacteriuria (ASB), what proportion of the population is aware of this condition and the quality of internet resources are currently unknown.

Objective

This study aimed to use an online crowdsourcing platform to explore general knowledge and internet search strategies, along with the quality of information, on ASB.

Study Design

An online survey was administered through a crowdsourcing platform to women 50 years or older via Qualtrics, which is a sophisticated online survey tool. Participants completed a survey on ASB, and participants were asked how they would search the internet for information both on urinary test results and on ASB. Outcomes included survey responses, and qualitative data were coded and analyzed thematically. χ2 Testing and regression modeling were used to look for variables associated with concern for ASB.

Results

There were a total of 518 participants who passed attention check qualifications, and only 45 respondents (8.7%) had heard of ASB. Many were concerned about progress to a worsening infection (n = 387 [77.6%]). When controlling for confounders, education beyond a college degree was not associated with a lower concern for ASB when compared with those with a high school education or less (adjusted odds ratio, 0.63; 95% confidence interval, 0.25–1.55; P = 0.31). Medical providers were the target audience for a majority of the websites, and many of the patient-facing results were of poor quality.

Conclusions

Our national survey of women demonstrated a prevalent knowledge deficit surrounding ASB. We must seek to create high-quality, readily available, patient-facing information to increase awareness of ASB, allay concerns, and increase antibiotic stewardship.
Cereal weevils' antimicrobial peptides: at the crosstalk between development, endosymbiosis and immune response
Authors: Galambos N. , Vincent-Monegat C. , Vallier A. , Parisot N. , Heddi A. , Zaidman-Rémy A.
Published: March 2024

Interactions between animals and microbes are ubiquitous in nature and strongly impact animal physiology. These interactions are shaped by the host immune system, which responds to infections and contributes to tailor the associations with beneficial microorganisms. In many insects, beneficial symbiotic associations not only include gut commensals, but also intracellular bacteria, or endosymbionts. Endosymbionts are housed within specialized host cells, the bacteriocytes, and are transmitted vertically across host generations. Host–endosymbiont co-evolution shapes the endosymbiont genome and host immune system, which not only fights against microbial intruders, but also ensures the preservation of endosymbionts and the control of their load and location. The cereal weevilSitophilusspp. is a remarkable model in which to study the evolutionary adaptation of the immune system to endosymbiosis owing to its binary association with a unique, relatively recently acquired nutritional endosymbiont,Sodalis pierantonius. This Gram-negative bacterium has not experienced the genome size shrinkage observed in long-term endosymbioses and has retained immunogenicity. We focus here on the sixteen antimicrobial peptides (AMPs) identified in theSitophilus oryzaegenome and their expression patterns in different tissues, along host development or upon immune challenges, to address their potential functions in the defensive response and endosymbiosis homeostasis along the insect life cycle.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
Decreasing hearing ability does not lead to improved visual speech extraction as revealed in a neural speech tracking paradigm
Authors: Haider Chandra Leon , Hauswald Anne , Weisz Nathan
Published: March 2024

The use of visual speech is thought to be especially important in situations where acoustics are unclear and in individuals with hearing impairment. To investigate this in a neural speech tracking paradigm, we measured MEG in sixty-seven mid- to old-age individuals during audiovisual (AV), audio-only (A), and visual-only (V) speech in the context of face masks. First, we could extend previous findings by showing that not only in young normal-hearing individuals but also in aging individuals with decreasing hearing ability the brain is superior in neurally tracking the acoustic spectrogram in AV compared to A presentations, especially in multi-speaker situations. The addition of visual lip movements further increases this benefit. Second, we could show that neural speech tracking in individuals with lower levels of hearing ability is affected more by face masks. However, in this population, the effect seems to be a composite of blocked visual speech and distorted acoustics. Third, we could confirm previous findings, that the neural benefit of visual speech varies strongly across individuals. We show that this general individual ability predicts how much people engage in visual speech tracking in difficult AV listening situations. Interestingly, this was not correlated with hearing thresholds and therefore does seem to be a widely used compensatory strategy in the hearing impaired.
Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats
Authors: King Christopher P. , Chitre Apurva S. , Leal-Gutiérrez Joel D. , Tripi Jordan A. , Hughson Alesa R. , Horvath Aidan P. , Lamparelli Alexander C. , George Anthony , Martin Connor , St. Pierre Celine L. , Sanches Thiago , Bimschleger Hannah V. , Gao Jianjun , Cheng Riyan , Nguyen Khai-Minh , Holl Katie L. , Polesskaya Oksana , Ishiwari Keita , Chen Hao , Solberg Woods Leah C. , Palmer Abraham A. , Robinson Terry E. , Flagel Shelly B. , Meyer Paul J.
Published: March 2024

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli (“cues”). Rats exhibited either cue-directed “sign-tracking” behavior or food-cup directed “goal-tracking” behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability,h2= .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes (e.g. Tenm4,Mir708) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes (e.g. Wnt11, Pak1) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.
Experimental evolution of a reduced bacterial chemotaxis network
Authors: Kargeti Manika , Kalita Irina , Hoch Sarah , Ratnikava Maryia , Xu Wenhao , Ni Bin , Dy Ron Leonard , Colin Remy , Sourjik Victor
Published: March 2024

Chemotaxis allows bacteria to follow chemical gradients by comparing their environment over time and adjusting their swimming behavior accordingly. The chemotaxis signaling pathway is highly conserved among all chemotactic bacteria. The system comprises two modules: one for environmental sensing and signal transduction toward the flagellar motor, and the other for adapting to the constant level of background stimulation and providing short-term memory for temporal comparisons. Previous experimental analysis and mathematical modeling have suggested that all components of the paradigmatic chemotaxis pathways inEscherichia coliare essential. This indicates that it may contain a minimal set of protein components necessary to mediate gradient sensing and behavioral response. To test this assumption, here we subjected strains carrying deletions in chemotaxis genes to experimental laboratory evolution. We observed that the core components of the chemotaxis pathway are indeed essential. However, the absence of individual auxiliary pathway proteins, including the adaptation enzymes that are conserved in a vast majority of bacteria, and the phosphatase, could be compensated for to varying degrees by changes in other pathway components. Our results suggest that the experimental evolution of these deletion strains has led to the emergence of alternative strategies for bacterial chemotaxis, demonstrating the surprisingly rapid evolvability of this signaling network.
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release
Authors: Poppinga J , Barret N.J. , Cornelisse L.N. , Verhage M. , van Weering J.R.T.
Published: March 2024

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how SNX4 affects synapse function remains unknown. We generated a conditional SNX4 knock-out mouse model and report that SNX4 cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. SNX4 depletion did not affect vesicle recycling, basic autophagic flux or the levels and localization of SNARE-protein VAMP2/synaptobrevin-2. However, SNX4 depletion affected synapse ultrastructure: an increase in docked synaptic vesicles at the active zone, while the overall vesicle number was normal, and a decreased active zone length. These effects together lead to a substantially increased density of docked vesicles per release site. In conclusion, SNX4 is a negative regulator of synaptic vesicle docking and release. These findings suggest a role for SNX4 in synaptic vesicle recruitment at the active zone.
Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotype and phenotype in chronic lymphocytic leukemia
Authors: Black Gage S. , Huang Xiaomeng , Qiao Yi , Moos Philip , Sampath Deepa , Stephens Deborah M. , Woyach Jennifer A. , Marth Gabor T.
Published: March 2024

Bruton's tyrosine kinase (BTK) inhibitors are effective for the treatment of chronic lymphocytic leukemia (CLL) due to BTK's role in B cell survival and proliferation. Treatment resistance is most commonly caused by the emergence of the hallmark BTKC481S mutation that inhibits drug binding. In this study, we aimed to investigate whether the presence of additional CLL driver mutations in cancer subclones harboring a BTKC481S mutation accelerates subclone expansion. In addition, we sought to determine whether BTK-mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones. To achieve these goals, we employ our recently published method (Qiao et al. 2024) that combines bulk DNA sequencing and single-cell RNA sequencing (scRNA-seq) data to genotype individual cells for the presence or absence of subclone-defining mutations. While the most common approach for scRNA-seq includes short-read sequencing, transcript coverage is limited due to the vast majority of the reads being concentrated at the priming end of the transcript. Here, we utilized MAS-seq, a long-read scRNAseq technology, to substantially increase transcript coverage across the entire length of the transcripts and expand the set of informative mutations to link cells to cancer subclones in six CLL patients who acquired BTKC481S mutations during BTK inhibitor treatment. We found that BTK-mutated subclones often acquire additional mutations in CLL driver genes, leading to faster subclone proliferation. When examining subclone-specific gene expression, we found that in one patient, BTK-mutated subclones are transcriptionally distinct from the rest of the malignant B cell population with an overexpression of CLL-relevant genes.
Accelerating the continuous community sharing of digital neuromorphology data
Authors: Tecuatl Carolina , Ljungquist Bengt , Ascoli Giorgio A.
Published: March 2024

The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.Org is the largest online collection of freely available digital neural reconstructions and related metadata and is continuously updated with new uploads. Earlier in the project, we released multiple datasets together yearly, but this process caused an average delay of several months in making the data public. Moreover, in the past 5 years, >80% of invited authors agreed to share their data with the community via NeuroMorpho.Org, up from <20% in the first 5 years of the project. In the same period, the average number of reconstructions per publication increased 600%, creating the need for automatic processing to release more reconstructions in less time. The progressive automation of our pipeline enabled the transition to agile releases of individual datasets as soon as they are ready. The overall time from data identification to public sharing decreased by 63.7%; 78% of the datasets are now released in less than 3 months with an average workflow duration below 40 days. Furthermore, the mean processing time per reconstruction dropped from 3 hours to 2 minutes. With these continuous improvements, NeuroMorpho.Org strives to forge a positive culture of open data. Most importantly, the new, original research enabled through reuse of datasets across the world has a multiplicative effect on science discovery, benefiting both authors and users.
Highly Pathogenic Avian Influenza A (H5N1) Suspected in penguins and shags on the Antarctic Peninsula and West Antarctic Coast
Authors: León Fabiola , Le Bohec Céline , Pizarro Eduardo J. , Baille Loïcka , Cristofari Robin , Houstin Aymeric , Zitterbart Daniel P. , Barriga Gonzalo , Poulin Elie , Vianna Juliana A.
Published: March 2024

Suspected cases of Highly Pathogenic Avian Influenza (H5N1) were detected in Adélie penguins and Antarctic shags at the southernmost latitude so far in Antarctica, at two breeding sites out of 13 visited, using highly specific PCR assay. These first records mark the progression of the H5N1 panzootic into Antarctica.