bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-related stigma, depression and suicidal ideation among HIV-positive MSM in China: a moderated mediation model
Authors: Fu Jiaqi , Chen Xu , Dai Zhenwei , Huang Yiman , Xiao Weijun , Wang Hao , Si Mingyu , Wu Yijin , Zhang Ling , Jing Shu , Liu Xin , Yu Fei , Mi Guodong , Su Xiao-You
Published: October 2023

Background

As the HIV epidemic among MSM in China continues, Chinese men who have sex with men (MSM) face various mental health difficulties, including suicide ideation, depression, and stigma. The current study aims to assess the mechanisms between HIV-related stigma, depression, and suicidal ideation among MSM in China.

Methods

This national cross-sectional study was completed on the geosocial networking application (GSN) app, Blued, from December 2020 to March 2021. We used the HIV Stigma Scale and the Center for Epidemiologic Studies Depression Scale (CES-D10) to measure HIV stigma and depression, respectively. Suicidal ideation was measured by the suicidal ideation-related item. Descriptive analyses, logistic regression, and structural equation modeling (SEM) were used for data analysis.

Results

A total of 244 HIV-positive MSM were included in the analysis. The mediation model revealed that the direct pathway of perceived HIV-related stigma on suicidal ideation was significant (standardized pathway coefficient = 0.07), and the indirect pathway of perceived HIV-related stigma on suicidal ideation via depression was also significant (standardized pathway coefficient = 0.04). There was a partial mediating effect of depression in the association between perceived HIV-related stigma and suicidal ideation.

Conclusions

Our study found that both perceived HIV-related stigma and depression were associated with suicidal ideation among HIV-positive MSM in China, and that depression could serve as a mediator between HIV-related stigma and suicidal ideation. Targeted interventions regarding HIV-related stigma and depression should be taken into account to reduce suicidal ideation among HIV-positive MSM in China.
A transvaginal ultrasound-based diagnostic calculator for uterus post-cesarean scar defect
Authors: Allameh Zahra , Rouholamin Safoura , Rasti Sina , Adibi Atoosa , Foroughi Zahra , Goharian Maryam , Rad Mehrdad Rabiee , Dabaghi Ghazal Ghasempour
Published: October 2023

Background

A cesarean scar defect (CSD) is incomplete healing of the myometrium at the site of a prior cesarean section (CS), complicating more than half of all cesarean sections. While transvaginal ultrasound (TVU) is the most common modality for diagnosing this defect, hysteroscopy remains the gold standard. We aimed to develop an efficient diagnostic tool for CSD among women with abnormal uterine bleeding (AUB) by integrating TVU findings and participants’ demographic features.

Methods

A single-center cross-sectional study was conducted on 100 premenopausal and non-pregnant women with a history of CS complaining of AUB without a known systemic or structural etiology. Each participant underwent a hysteroscopy followed by a TVU the next day. The defect dimensions in TVU, patients’ age, and the number of previous CSs were integrated into a binary logistic regression model to evaluate their predictive ability for a hysteroscopy-confirmed CSD.

Results

Hysteroscopy identified 74 (74%) participants with CSD. The variables age, the number of CSs, defect length, and defect width significantly contributed to the logistic regression model to diagnose CSD with odds ratios of 9.7, 0.7, 2.6, and 1.7, respectively. The developed model exhibited accuracy, sensitivity, and specificity of 88.00%, 91.89%, and 76.92%, respectively. The area under the receiver operating curve was 0.955 (P-value < 0.001).

Conclusion

Among non-pregnant women suspected of CSD due to AUB, looking at age, the number of previous CSs, and TVU-based defect width and length can efficiently rule CSD out.
The effects of ginger supplementation on common gastrointestinal symptoms in patients with relapsing-remitting multiple sclerosis: a double-blind randomized placebo-controlled trial
Authors: Foshati Sahar , Poursadeghfard Maryam , Heidari Zahra , Amani Reza
Published: October 2023

Background

Gastrointestinal (GI) symptoms affect more than 80% of individuals with relapsing-remitting multiple sclerosis (RRMS). Ginger is widely known for its GI relieving properties. Therefore, we investigated the effect of ginger supplementation on common GI symptoms in RRMS patients.

Methods

This study was a 12-week double-blind parallel randomized controlled trial with a 3-week run-in period. The intervention (n = 26) and control (n = 26) groups received 500 mg ginger and placebo (as corn) supplements 3 times a day along with main meals, respectively. At the beginning and end of the trial, the frequency and severity of constipation, dysphagia, abdominal pain, diarrhea, bloating, belching, flatulence, heartburn, anorexia, and nausea were assessed using the visual analogue scale ranging from 0 to 100 mm. Totally, 49 participants completed the study. However, data analysis was performed on all 52 participants based on the intention-to-treat principle.

Results

In comparison with placebo, ginger supplementation resulted in significant or near-significant reductions in the frequency (-23.63 ± 5.36 vs. 14.81 ± 2.78,P < 0.001) and severity (-24.15 ± 5.10 vs. 11.39 ± 3.23,P < 0.001) of constipation, the frequency (-12.41 ± 3.75 vs. 3.75 ± 1.82,P < 0.001) and severity (-13.43 ± 4.91 vs. 6.88 ± 2.69,P = 0.001) of nausea, the frequency (-9.31 ± 4.44 vs. 1.56 ± 4.05,P = 0.098) and severity (-11.57 ± 5.09 vs. 3.97 ± 3.99,P = 0.047) of bloating, and the severity of abdominal pain (-5.69 ± 3.66 vs. 3.43 ± 3.26,P = 0.069).

Conclusion

Ginger consumption can improve constipation, nausea, bloating, and abdominal pain in patients with RRMS.

Trial Registration

This trial was prospectively registered at the Iranian Registry of Clinical Trials (www.irct.ir) under the registration number IRCT20180818040827N3 on 06/10/2021.
“There is no one who helps you with it”: experiences of people with long COVID regarding medical care, therapeutic measures, and barriers in the German healthcare system: results of a qualitative study with four focus groups
Authors: Schmachtenberg Tim , Königs Gloria , Dragaqina Anita , Roder Sascha , Müller Frank , Müllenmeister Christina , Schröder Dominik , Dopfer-Jablonka Alexandra , Vieth Katharina , El-Sayed Iman
Published: October 2023

Background

Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures.

Methods

Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz.

Results

Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers’ lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID.

Conclusions

Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment.

Trial registration

The study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).
Perceptions and factors associated with the uptake of the community client-led antiretroviral therapy delivery model (CCLAD) at a large urban clinic in Uganda: a mixed methods study
Authors: Walusaga Happy Annet Gasaatura , Atuyambe Lynn M , Muddu Martin , Mpirirwe Ruth , Nangendo Joan , Kalibbala Dennis , Semitala Fred C. , Katahoire Anne R.
Published: October 2023

Introduction

Community Client-Led ART Delivery (CCLAD) is a community HIV care model. In this model, a group of persons living with HIV (PLHIV) in a specific location, take turns going to the HIV clinic to pick up Antiretroviral Treatment refills for members. The uptake of this model, however, remains low despite its improvements in patient retention. In this study, we explored PLHIV’s perceptions of this model and identified the factors associated with its low uptake.

Methods

This was a mixed methods study based on a retrospective review of records of PLHIV and in-depth interviews. We reviewed the medical records of people receiving ART to determine their current model of ART delivery and conducted in-depth interviews with 30 participants who were eligible to be enrolled in the CCLAD model at the Mulago ISS clinic. We performed logistic regression to identify factors associated with the uptake of the CCLAD model and inductive thematic analysis to explore PLHIV’s perceptions of the CCLAD model.

Results

A total of 776 PLHIV were sampled for the study, 545 (70.2%) of whom were female. The mean age (standard deviation) was 42 (± 9.3) years. Overall, 55 (7.1%) received ART using the CCLAD model. Compared to other ART-delivery models, CCLAD was associated with being on ART for at least eight years (AOR 3.72; 95% CI: 1.35–10.25) and having no prior missed clinic appointments (AOR 10.68; 95% CI: 3.31–34.55). Mixed perceptions were expressed about the CCLAD model. Participants interviewed appreciated CCLAD for its convenience and the opportunities it offered members to talk and support each other. Others however, expressed concerns about the process of group formation, and feeling detached from the health facility with consequences of lack of confidentiality.

Conclusion

The current uptake of the CCLAD model is lower than the national recommended percentage of 15%. Its uptake was associated with those who had been in care for a longer period and who did not miss appointments. Despite CCLAD being perceived as convenient and as promoting support among members, several challenges were expressed. These included complexities of group formation, fear of stigma and feelings of detachment from health facilities among others. So, while CCLAD presents a promising alternative ART delivery model, more attention needs to be paid to the processes of group formation and improved patient monitoring to address the feelings of detachment from the facility and facility staff.
Deep learning models of ultrasonography significantly improved the differential diagnosis performance for superficial soft-tissue masses: a retrospective multicenter study
Authors: Long Bin , Zhang Haoyan , Zhang Han , Chen Wen , Sun Yang , Tang Rui , Lin Yuxuan , Fu Qiang , Yang Xin , Cui Ligang , Wang Kun
Published: October 2023

Background

Most of superficial soft-tissue masses are benign tumors, and very few are malignant tumors. However, persistent growth, of both benign and malignant tumors, can be painful and even life-threatening. It is necessary to improve the differential diagnosis performance for superficial soft-tissue masses by using deep learning models. This study aimed to propose a new ultrasonic deep learning model (DLM) system for the differential diagnosis of superficial soft-tissue masses.

Methods

Between January 2015 and December 2022, data for 1615 patients with superficial soft-tissue masses were retrospectively collected. Two experienced radiologists (radiologists 1 and 2 with 8 and 30 years’ experience, respectively) analyzed the ultrasound images of each superficial soft-tissue mass and made a diagnosis of malignant mass or one of the five most common benign masses. After referring to the DLM results, they re-evaluated the diagnoses. The diagnostic performance and concerns of the radiologists were analyzed before and after referring to the results of the DLM results.

Results

In the validation cohort, DLM-1 was trained to distinguish between benign and malignant masses, with an AUC of 0.992 (95% CI: 0.980, 1.0) and an ACC of 0.987 (95% CI: 0.968, 1.0). DLM-2 was trained to classify the five most common benign masses (lipomyoma, hemangioma, neurinoma, epidermal cyst, and calcifying epithelioma) with AUCs of 0.986, 0.993, 0.944, 0.973, and 0.903, respectively. In addition, under the condition of the DLM-assisted diagnosis, the radiologists greatly improved their accuracy of differential diagnosis between benign and malignant tumors.

Conclusions

The proposed DLM system has high clinical application value in the differential diagnosis of superficial soft-tissue masses.
Influences of comorbidities on perioperative rehabilitation in patients with gastrointestinal cancers: a retrospective study
Authors: Seriu Naoto , Tsukamoto Shinji , Ishida Yukako , Yamanaka Nobuki , Mano Tomoo , Kobayashi Yasuyo , Sajiki-Ito Marina , Inagaki Yusuke , Tanaka Yuu , Sho Masayuki , Kido Akira
Published: October 2023

Background

Older patients are more likely to have comorbidities than younger patients, and multiple comorbidities are associated with mortality in patients with cancer. Therefore, we hypothesized that a functional comorbidity index could predict the therapeutic effects of rehabilitation.

Objectives

In this study, we investigate whether the comorbidities influenced the execution and therapeutic effects of rehabilitation.

Methods

A consecutive cohort of 48 patients with gastrointestinal cancer who underwent surgery between January 1 and November 30, 2020, was analyzed. Charlson Comorbidity Index (CCI) scores were calculated based on data derived from medical records. The primary outcomes were ambulation status, duration (days) from the start of postoperative rehabilitation, and length of hospital stay. We investigated the relationship between CCI scores and primary outcomes.

Results

The CCI did not correlate with the duration of rehabilitation or the length of hospital stay. Subsequently, patients with functional recovery problems were evaluated, and we identified the conditions that were not included in the list using CCI scores. Most conditions are associated with surgical complications. Furthermore, using the Clavien-Dindo classification (CDC), we assessed the clinical features of the severity of complications. We found that the length of stay and the duration to start rehabilitation were significantly longer in the patients with higher severity of surgical complications (CDC≧III) than in those with lower severity (CDC≦II).

Conclusions

Treatment-related conditions may significantly impact the perioperative period more than the original comorbidities. In addition to original comorbidities, events related to surgical complications should be assessed to determine the therapeutic effects of rehabilitation in patients with gastrointestinal cancer.
Factors associated with regional retention of physicians: a cross-sectional online survey of medical students and graduates in Japan
Authors: Koike Soichi , Okazaki Kentaro , Tokinobu Akiko , Matsumoto Masatoshi , Kotani Kazuhiko , Kataoka Hitomi
Published: October 2023

Background

Physician shortage and maldistribution is an urgent health policy issue requiring resolution. Determination of factors associated with regional retention and development of effective policy interventions will help to solve this issue. The purpose of the present study was to identify factors associated with regional retention and discuss their policy implications.

Methods

We conducted a cross-sectional online survey from February to March of 2022 for graduates from regional quotas (special quotas for medical schools to select students engaged in community medicine) and Jichi Medical University (JMU) and students at 10 medical schools including JMU. Completed surveys were obtained from 375 graduates and 1153 students. Questions included intention to continue to work in their home prefecture in the future, as well as background information and potential factors associated with regional retention. In the analyses, regional quotas and JMU were referred to as community medicine-oriented programs and schools (CMPS). We performed logistic regression analyses to identify factors associated with regional retention.

Results

Among the students, scholarship-bonded obligatory service, satisfaction with current life, intention to belong to ikyoku (a traditional physician allocation/training system in Japanese medical schools), and interest in general practice/family medicine were significantly positively associated with regional retention. Among the graduates, satisfaction with training environment, intention to belong to ikyoku, and recommending their program to high school students were significantly positively associated with regional retention. For students of CMPS, satisfaction with the career development program was positively associated with future regional retention. For graduates, this association was observed only in the crude analysis.

Conclusions

In addition to known factors such as interest in general practice/family medicine, intention to belong to ikyoku had a substantial impact on regional retention. The present results suggest that the career support system represented by ikyoku as well as a career development program are of potential importance for increasing regional retention through the mechanisms of a sense of belonging and a life-long education system. These findings provide useful information for the development of further policy interventions that interweave traditional and new systems to maximize their effectiveness.
Case report: JAK1/2 inhibition with baricitinib in the treatment of STING-associated vasculopathy with onset in infancy
Authors: Wu Jianqiang , Zhou Qing , Zhou Hua , Lu Meiping
Published: October 2023

Background

Gain-of-function mutations in STING1 (also known as TMEM173) which result in constitutive activation of STING, have been reported to cause STING-associated vasculopathy with onset in infancy (SAVI). Although a wider spectrum of associated manifestations and perturbations in disease onset have been observed since its description, the genotype-phenotype correlations are not definite, and there is no established treatment protocol for SAVI.

Case presentation

Herein, we report a kindred, heterozygous STING mutation (p.V155M) in which the 2-year-old proband suffered from severe interstitial lung disease (ILD) while her father was initially misdiagnosed with connective tissue disease associated with ILD at an adult age. Baricitinib was initiated after the diagnosis of SAVI in the proband combined with steroids, and during the 14-month follow-up, the respiratory symptoms were improved. However, as the improvement of laboratory indicators was limited, especially in autoimmune indices, and the lung CT images remained unaltered, it seems that JAK1/2 inhibition was unsatisfactory in completely controlling the inflammation of the disease in our study.

Conclusions

Baricitinib was shown to elicit some effect on the ILD but failed to control the inflammation of the disease completely. Further exploration of JAK inhibitors or other therapeutic strategies are needed to more optimally treat this inflammatory disease.
IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury
Authors: Vincent Jonathan C. , Garnett Colleen N. , Watson James B. , Higgins Emma K. , Macheda Teresa , Sanders Lydia , Roberts Kelly N. , Shahidehpour Ryan K. , Blalock Eric M. , Quan Ning , Bachstetter Adam D.
Published: October 2023

Neuroinflammation contributes to secondary injury cascades following traumatic brain injury (TBI), with alternating waves of inflammation and resolution. Interleukin-1 (IL-1), a critical neuroinflammatory mediator originating from brain endothelial cells, microglia, astrocytes, and peripheral immune cells, is acutely overexpressed after TBI, propagating secondary injury and tissue damage. IL-1 affects blood–brain barrier permeability, immune cell activation, and neural plasticity. Despite the complexity of cytokine signaling post-TBI, we hypothesize that IL-1 signaling specifically regulates neuroinflammatory response components. Using a closed-head injury (CHI) TBI model, we investigated IL-1's role in the neuroinflammatory cascade with a new global knock-out (gKO) mouse model of the IL-1 receptor (IL-1R1), which efficiently eliminates all IL-1 signaling. We found that IL-1R1 gKO attenuated behavioral impairments 14 weeks post-injury and reduced reactive microglia and astrocyte staining in the neocortex, corpus callosum, and hippocampus. We then examined whether IL-1R1 loss altered acute neuroinflammatory dynamics, measuring gene expression changes in the neocortex at 3, 9, 24, and 72 h post-CHI using the NanoString Neuroinflammatory panel. Of 757 analyzed genes, IL-1R1 signaling showed temporal specificity in neuroinflammatory gene regulation, with major effects at 9 h post-CHI. IL-1R1 signaling specifically affected astrocyte-related genes, selectively upregulating chemokines like Ccl2, Ccl3, and Ccl4, while having limited impact on cytokine regulation, such as Tnfα. This study provides further insight into IL-1R1 function in amplifying the neuroinflammatory cascade following CHI in mice and demonstrates that suppression of IL-1R1 signaling offers long-term protective effects on brain health.
CRISPR–Cas system to discover host-virus interactions in Flaviviridae
Authors: Ramezannia Zahra , Shamekh Ali , Bannazadeh Baghi Hossein
Published: October 2023

The Flaviviridae virus family members cause severe human diseases and are responsible for considerable mortality and morbidity worldwide. Therefore, researchers have conducted genetic screens to enhance insight into viral dependency and develop potential anti-viral strategies to treat and prevent these infections. The host factors identified by the clustered regularly interspaced short palindromic repeats (CRISPR) system can be potential targets for drug development. Meanwhile, CRISPR technology can be efficiently used to treat viral diseases as it targets both DNA and RNA. This paper discusses the host factors related to the life cycle of viruses of this family that were recently discovered using the CRISPR system. It also explores the role of immune factors and recent advances in gene editing in treating flavivirus-related diseases. The ever-increasing advancements of this technology may promise new therapeutic approaches with unique capabilities, surpassing the traditional methods of drug production and treatment.
Sustainability, spread, and scale in trials using audit and feedback: a theory-informed, secondary analysis of a systematic review
Authors: Laur Celia , Ladak Zeenat , Hall Alix , Solbak Nathan M. , Nathan Nicole , Buzuayne Shewit , Curran Janet A. , Shelton Rachel C. , Ivers Noah
Published: October 2023

Background

Audit and feedback (A&F) is a widely used implementation strategy to influence health professionals’ behavior that is often tested in implementation trials. This study examines how A&F trials describe sustainability, spread, and scale.

Methods

This is a theory-informed, descriptive, secondary analysis of an update of the Cochrane systematic review of A&F trials, including all trials published since 2011. Keyword searches related to sustainability, spread, and scale were conducted. Trials with at least one keyword, and those identified from a forward citation search, were extracted to examine how they described sustainability, spread, and scale. Results were qualitatively analyzed using the Integrated Sustainability Framework (ISF) and the Framework for Going to Full Scale (FGFS).

Results

From the larger review, n = 161 studies met eligibility criteria. Seventy-eight percent (n = 126) of trials included at least one keyword on sustainability, and 49% (n = 62) of those studies (39% overall) frequently mentioned sustainability based on inclusion of relevant text in multiple sections of the paper. For spread/scale, 62% (n = 100) of trials included at least one relevant keyword and 51% (n = 51) of those studies (31% overall) frequently mentioned spread/scale. A total of n = 38 studies from the forward citation search were included in the qualitative analysis. Although many studies mentioned the need to consider sustainability, there was limited detail on how this was planned, implemented, or assessed. The most frequent sustainability period duration was 12 months. Qualitative results mapped to the ISF, but not all determinants were represented. Strong alignment was found with the FGFS for phases of scale-up and support systems (infrastructure), but not for adoption mechanisms. New spread/scale themes included (1) aligning affordability and scalability; (2) balancing fidelity and scalability; and (3) balancing effect size and scalability.

Conclusion

A&F trials should plan for sustainability, spread, and scale so that if the trial is effective, the benefits can continue. A deeper empirical understanding of the factors impacting A&F sustainability is needed. Scalability planning should go beyond cost and infrastructure to consider other adoption mechanisms, such as leadership, policy, and communication, that may support further scalability.

Trial registration

Registered with Prospero in May 2022. CRD42022332606.
Exosomal long noncoding RNA MLETA1 promotes tumor progression and metastasis by regulating the miR-186-5p/EGFR and miR-497-5p/IGF1R axes in non-small cell lung cancer
Authors: Hsu Xiu-Rui , Wu Jia-En , Wu Yi-Ying , Hsiao Sheng-Yen , Liang Jui-Lin , Wu Ya-Ju , Tung Chia-Hao , Huang Meng-Fan , Lin Ming-Shiu , Yang Pan-Chyr , Chen Yuh-Ling , Hong Tse-Ming
Published: October 2023

Background

Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear.

Methods

Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs.

Results

Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients.

Conclusions

This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment.
Do we need standardized management after termination-of-resuscitation attempts? Autoresuscitation in a 67-year-old woman
Authors: Pasierski Janina , Kleger Gian-Reto , Imboden Paul
Published: October 2023

Background

Autoresuscitation is the phenomenon of spontaneous return of circulation after cessation of CPR, also known as the Lazarus phenomenon. Most of the evidence is based on case reports and a few systematic reviews. The occurrence of autoresuscitation may lead to self-reproach and dismay in affected emergency personnel and may rise questions about the correct procedure after terminating resuscitative efforts. In contrast to existing cardiac arrest guidelines there is no standardized approach to terminating resuscitative attempts.

Case

We report a case of out of hospital autoresuscitation in a 67-year-old female after 60 min of advanced cardiac life support. After shock refractory shockable rhythm, we recorded pulseless electrical activity and fixed pupils, consequently resuscitation was terminated. About 50 min later the patient surprisingly showed signs of life. Due to the suggestive history a coronary angiography was performed, showing severe coronary heart disease which necessitated surgical intervention. After ACBP surgery and intensive care followed by treatment on the cardiological ward, she was finally discharged to neurological rehabilitation.

Conclusion

As already proposed by existing literature, there should be at least a 10-min interval of close monitoring after abandoning CPR. Transport of a deceased patient should only take place after secure signs of death can be detected. Further investigation is needed to determine which patients are most likely to benefit from an extended observation period. Our case reports highlights the difficulties in death declaration and the importance of close monitoring after abandoning CPR.
Human parechovirus meningitis in children: state of the art
Authors: Bozzola Elena , Barni Sarah , Barone Chiara , Perno Carlo Federico , Maggioni Andrea , Villani Alberto
Published: October 2023

Human Parechovirus is a common cause of infection occurring especially during the first years of life. It may present with a broad spectrum of manifestations, ranging from a pauci-symptomatic infection to a sepsis-like or central nervous system disease. Aim of this study is to explore the knowledge on Parechovirus meningitis. According to the purpose of the study, a systematic review of the literature focusing on reports on central nervous system. Parechovirus infection of children was performed following PRISMA criteria. Out of the search, 304 papers were identified and 81 records were included in the revision dealing with epidemiology, clinical manifestations, laboratory findings, imaging, therapy and outcome. Parechovirus meningitis incidence may vary all over the world and outbreaks may occur. Fever is the most common symptom, followed by other non-specific signs and symptoms including irritability, poor feeding, skin rash or seizures. Although several reports describe favourable short-term neurodevelopmental outcomes at discharge after Parechovirus central nervous system infection, a specific follow up and the awareness on the risk of sequelae should be underlined in relation to the reported negative outcome. Evidence seems to suggest a correlation between magnetic imaging resonance alteration and a poor outcome.
How I manage differential gas exchange in peripheral venoarterial extracorporeal membrane oxygenation
Authors: Asija Richa , Fried Justin A. , Siddall Eric C. , Mullin Dana A. , Agerstrand Cara L. , Brodie Daniel , Sonett Joshua R. , Lemaitre Philippe H. , Abrams Darryl
Published: October 2023

Dual circulation is a common but underrecognized physiological occurrence associated with peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Competitive flow will develop between blood ejected from the heart and blood travelling retrograde within the aorta from the ECMO reinfusion cannula. The intersection of these two competitive flows is referred to as the “mixing point”. The location of this mixing point, which depends upon the relative strengths of the native and extracorporeal pumps, will determine which regions of the body are perfused with blood ejected from the left ventricle and which regions are perfused by reinfused blood from the ECMO circuit, effectively establishing dual circulations. Because gas exchange within these circulations is dictated by the native lungs and membrane lung, respectively, oxygenation and carbon dioxide removal may differ between regions—depending on how well gas exchange is preserved within each circulation—potentially leading to differential oxygenation or differential carbon dioxide, each of which may have important clinical implications. In this perspective, we address the identification and management of dual circulation and differential gas exchange through various clinical scenarios of venoarterial ECMO. Recognition of dual circulation, proper monitoring for differential gas exchange, and understanding the various strategies to resolve differential oxygenation and carbon dioxide may allow for more optimal patient management and improved clinical outcomes.
Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates
Authors: Zheng Shijie C. , Stein-O’Brien Genevieve , Boukas Leandros , Goff Loyal A. , Hansen Kasper D.
Published: October 2023

Background

RNA velocity analysis of single cells offers the potential to predict temporal dynamics from gene expression. In many systems, RNA velocity has been observed to produce a vector field that qualitatively reflects known features of the system. However, the limitations of RNA velocity estimates are still not well understood.

Results

We analyze the impact of different steps in the RNA velocity workflow on direction and speed. We consider both high-dimensional velocity estimates and low-dimensional velocity vector fields mapped onto an embedding. We conclude the transition probability method for mapping velocity estimates onto an embedding is effectively interpolating in the embedding space. Our findings reveal a significant dependence of the RNA velocity workflow on smoothing via the k-nearest-neighbors (k-NN) graph of the observed data. This reliance results in considerable estimation errors for both direction and speed in both high- and low-dimensional settings when the k-NN graph fails to accurately represent the true data structure; this is an unknown feature of real data. RNA velocity performs poorly at estimating speed in both low- and high-dimensional spaces, except in very low noise settings. We introduce a novel quality measure that can identify when RNA velocity should not be used.

Conclusions

Our findings emphasize the importance of choices in the RNA velocity workflow and highlight critical limitations of data analysis. We advise against over-interpreting expression dynamics using RNA velocity, particularly in terms of speed. Finally, we emphasize that the use of RNA velocity in assessing the correctness of a low-dimensional embedding is circular.
Y-mediated optimization of 3DG-PbO2 anode for electrochemical degradation of PFOS
Authors: Duan Xiaoyue , Ning Ziqi , Wang Weiyi , Li Yitong , Zhao Xuesong , Liu Liyue , Li Wenqian , Chang Limin
Published: October 2023

In our previous study, the three-dimensional graphene-modified PbO2 (3DG-PbO2) anode was prepared for the effective degradation of perfluorooctanesulfonat (PFOS) by the electrochemical oxidation process. However, the mineralization efficiency of PFOS at the 3DG-PbO2 anode still needs to be further improved due to the recalcitrance of PFOS. Thus, in this study, the yttrium (Y) was doped into the 3DG-PbO2 film to further improve the electrochemical activity of the PbO2 anode. To optimize the doping amount of Y, three Y and 3DG codoped PbO2 anodes were fabricated with different Y3+ concentrations of 5, 15, and 30 mM in the electroplating solution, which were named Y/3DG-PbO2-5, Y/3DG-PbO2-15 and Y/3DG-PbO2-30, respectively. The results of morphological, structural, and electrochemical characterization revealed that doping Y into the 3DG-PbO2 anode further refined the β-PbO2 crystals, increased the oxygen evolution overpotential and active sites, and reduced the electron transfer resistance, resulting in a superior electrocatalytic activity. Among all the prepared anodes, the Y/3DG-PbO2-15 anode exhibited the best activity for electrochemical oxidation of PFOS. After 120 min of electrolysis, the TOC removal efficiency was 80.89% with Y/3DG-PbO2-15 anode, greatly higher than 69.13% with 3DG-PbO2 anode. In addition, the effect of operating parameters on PFOS removal was analyzed by response surface, and the obtained optimum values of current density, initial PFOS concentration, pH, and Na2SO4 concentration were 50 mA/cm2, 12.21 mg/L, 5.39, and 0.01 M, respectively. Under the optimal conditions, the PFOS removal efficiency reached up to 97.16% after 40 min of electrolysis. The results of the present study confirmed that the Y/3DG-PbO2 was a promising anode for electrocatalytic oxidation of persistent organic pollutants.
A novel transcriptional repressor specifically regulates xylanase gene 1 in Trichoderma reesei
Authors: Xu Wenqiang , Ren Yajing , Xia Yuxiao , Liu Lin , Meng Xiangfeng , Chen Guanjun , Zhang Weixin , Liu Weifeng
Published: October 2023

Background

The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering.

Results

To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter.

Conclusions

XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei.
Cysteine facilitates the lignocellulolytic response of Trichoderma guizhouense NJAU4742 by indirectly up-regulating membrane sugar transporters
Authors: Liu Yang , Li Tuo , Zhu Han , Zhou Yihao , Shen Qirong , Liu Dongyang
Published: October 2023

Background

Filamentous fungi possess a rich CAZymes system, which is widely studied and applied in the bio-conversion of plant biomass to alcohol chemicals. Carbon source acquisition is the fundamental driver for CAZymes-producing sustainability and secondary metabolism, therefore, a deeper insight into the regulatory network of sugar transport in filamentous fungi has become urgent.

Results

This study reports an important linkage of sulfur assimilation to lignocellulose response of filamentous fungus. Inorganic sulfur addition facilitated biodegradation of rice straw by Trichodermaguizhouense NJAU4742. Cysteine and glutathione were revealed as major intracellular metabolites responsive to sulfur addition by metabolomics, cysteine content was increased in this process and glutathione increased correspondingly. Two membrane sugar transporter genes, Tgmst1 and Tgmst2, were identified as the critical response genes significantly up-regulated when intracellular cysteine increased. Tgmst1 and Tgmst2 were both positively regulated by the glucose regulation-related protein (GRP), up-regulation of both Tgmst1 and Tggrp can cause a significant increase in intracellular glucose. The transcriptional regulatory function of GRP mainly relied on GSH-induced glutathionylation, and the transcription activating efficiency was positively related to the glutathionylation level, furthermore, DTT-induced deglutathionylation resulted in the down-regulation of downstream genes.

Conclusions

Inorganic sulfur addition induces a rise in intracellular Cys content, and the conversion of cysteine to glutathione caused the increase of glutathionylation level of GRP, which in turn up-regulated Tgmst1 and Tgmst2. Subsequently, the sugar transport efficiency of single cells was improved, which facilitated the maintenance of vigorous CAZymes metabolism and the straw-to-biomass conversion.
Nascent transcription upon interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines
Authors: Ramirez Daniel , B. Chuong Edward , D. Dowell Robin
Published: October 2023

Objectives

The interferon-triggered innate immune response has been observed to be under strong diversifying selection to counteract the many pathogens hosts have to defend against. In particular, rewiring of gene transcription regulation allows organisms to rapidly acquire new phenotypes by removing and adding genes into the innate immune gene network. Dissecting the molecular processes by which this rewiring takes place, either by changing the DNA regulatory elements or by changing the activity of the regulators across species, is key to better understand this evolutionary process.

Data description

To better comprehend the evolutionary dynamics that have occurred in the initial transcriptional response to interferon in primates, we present Precision Run-On (PRO-seq) datasets made after 1 h of interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines. Further, we tested the difference between using either species’ cognate interferon versus using the other orthologous interferon to account for any potential impacts in the interaction of the orthologous interferons with their cellular membrane receptors. This data provides insights into the regulatory mechanisms that drive species-specific responses to environmental perturbations, such as the one driven by the interactions of pathogens and their hosts.
Social contact patterns among employees in U.S. long-term care facilities during the COVID-19 pandemic, December 2020 to June 2021
Authors: Zissette Seth , Kiti Moses C. , Bennett Brady W. , Liu Carol Y. , Nelson Kristin N. , Zelaya Alana , Kellogg Joseph T. , Johnson II Theodore M. , Clayton Pam , Fridkin Scott K. , Omer Saad B. , Lopman Benjamin A. , Adams Carly
Published: October 2023

Objective

We measured contact patterns using social contact diaries for 157 U.S. long-term care facility employees from December 2020 - June 2021. These data are crucial for analyzing mathematical transmission models and for informing healthcare setting infection control policy.

Results

The median number of daily contacts was 10 (IQR 8–11). Household contacts were more likely partially masked than fully masked, more likely to involve physical contact, and longer in duration compared to facility contacts.
Limiting life-sustaining treatment for very old ICU patients: cultural challenges and diverse practices
Authors: Beil Michael , van Heerden Peter Vernon , Joynt Gavin M. , Lapinsky Stephen , Flaatten Hans , Guidet Bertrand , de Lange Dylan , Leaver Susannah , Jung Christian , Forte Daniel Neves , Bin Du , Elhadi Muhammed , Szczeklik Wojciech , Sviri Sigal
Published: October 2023

Background

Decisions about life-sustaining therapy (LST) in the intensive care unit (ICU) depend on predictions of survival as well as the expected functional capacity and self-perceived quality of life after discharge, especially in very old patients. However, prognostication for individual patients in this cohort is hampered by substantial uncertainty which can lead to a large variability of opinions and, eventually, decisions about LST. Moreover, decision-making processes are often embedded in a framework of ethical and legal recommendations which may vary between countries resulting in divergent management strategies.

Methods

Based on a vignette scenario of a multi-morbid 87-year-old patient, this article illustrates the spectrum of opinions about LST among intensivsts with a special interest in very old patients, from ten countries/regions, representing diverse cultures and healthcare systems.

Results

This survey of expert opinions and national recommendations demonstrates shared principles in the management of very old ICU patients. Some guidelines also acknowledge cultural differences between population groups. Although consensus with families should be sought, shared decision-making is not formally required or practised in all countries.

Conclusions

This article shows similarities and differences in the decision-making for LST in very old ICU patients and recommends strategies to deal with prognostic uncertainty. Conflicts should be anticipated in situations where stakeholders have different cultural beliefs. There is a need for more collaborative research and training in this field.