bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow induces common and specific transcriptional changes in renal tubular epithelial cells involving the PI3K pathway
Authors: Tröndle Kevin , Rizzo Ludovica , Pichler Roman , Zimmermann Stefan , Lienkamp Soeren S. 
Published: December 2023

AbstractFlow‐induced shear stress affects renal epithelial cells in the nephron tubule with potential implications for differential functionalities of the individual segments. Disruptions of cellular mechanosensation or flow conditions are associated with the development and progression of various renal diseases. This study investigates the effects of flow on the transcriptome of various renal tubular epithelial cell types. We analyzed the transcriptome of induced renal epithelial cells (iREC) cultured under physiological flow (0.57 ± 0.05 dyn/cm2) or in static conditions for 72 h. RNA sequencing showed 861 differentially expressed genes (DEGs), with 503 up‐ and 358 downregulated under flow. DEGs were linked to extracellular matrix (ECM) components (e.g. Col1a1, Col4a3, Col4a4, Fn1, Smoc2), junctions (Gja1, Tubb5), channel activities (Abcc4, Aqp1), and transcription factors (Foxq1, Lgr6). Next, we performed a meta‐analysis comparing our data with three published datasets that subjected epithelial cell lines from distinct segments to flow, including proximal tubule and collecting duct cells. We found that TGF‐ß, p53, MAPK, and PI3K are common flow‐regulated pathways. Tfrc expression and thus the capability of iron uptake is commonly upregulated under flow. Many DEGs were related to kidney diseases, such as fibrosis (e.g. Tgfb1‐3 and Serpine1). To obtain further mechanistic insights we investigated the role of the PI3K pathway in flow sensing. Applying flow and inhibition of PI3K showed significantly altered expression of transcripts related to ECM remodeling, angiogenesis, and ion transport. This suggests that the PI3K pathway is a critical mediator in flow‐dependent cellular processes and gene expression, potentially influencing renal development and tissue remodeling. Finally, we derived a cross‐cell‐line summary of common as well as segment‐specific transcriptomic effects, thus providing insights into the molecular mechanisms underlying flow sensing in the nephron tubule.
Overcoming barriers to recognizing and reporting child abuse
Authors: Harding-Bremner Meredith 
Published: December 2023

ABSTRACT
Infants and children under age 3 years have the highest risk of dying from child abuse and neglect. Clinicians treating children must recognize and report child abuse. Barriers to consistent recognition and reporting leave children in harm's way. Often, the signs of abuse in very young children are subtle, and clinicians may fail to recognize and report these signs. Clinicians also must understand the role of bias in the reporting of child abuse and ways to address abuse individually and as part of a larger system.
ALDOB/KAT2A interactions epigenetically modulate TGF-β expression and T cell functions in hepatocellular carcinogenesis
Authors: Yin Chunzhao , Zhang Cunzhen , Wang Yongqiang , Liu Guijun , Wang Ningning , Liang Ningning , Zhang Lili , Tu Qiaochu , Lv Jingwen , Jiang Huimin , Ma Haoran , Du Chenxi , Li Min , He Xuxiao , Chen Shiting , Guo Jiacheng , Li Shengxian , Qin Jun , Li Nan , Tao Yongzhen , Yin Huiyong 
Published: December 2023

Background and Aims:
Cross talk between tumor cells and immune cells enables tumor cells to escape immune surveillance and dictate responses to immunotherapy. Previous studies have identified that downregulation of the glycolytic enzyme fructose-1,6-bisphosphate aldolase B (ALDOB) in tumor cells orchestrated metabolic programming to favor HCC. However, it remains elusive whether and how ALDOB expression in tumor cells affects the tumor microenvironment in HCC.

Approach and Results:
We found that ALDOB downregulation was negatively correlated with CD8+ T cell infiltration in human HCC tumor tissues but in a state of exhaustion. Similar observations were made in mice with liver-specific ALDOB knockout or in subcutaneous tumor models with ALDOB knockdown. Moreover, ALDOB deficiency in tumor cells upregulates TGF-β expression, thereby increasing the number of Treg cells and impairing the activity of CD8+ T cells. Consistently, a combination of low ALDOB and high TGF-β expression exhibited the worst overall survival for patients with HCC. More importantly, the simultaneous blocking of TGF-β and programmed cell death (PD) 1 with antibodies additively inhibited tumorigenesis induced by ALDOB deficiency in mice. Further mechanistic experiments demonstrated that ALDOB enters the nucleus and interacts with lysine acetyltransferase 2A, leading to inhibition of H3K9 acetylation and thereby suppressing TGFB1 transcription. Consistently, inhibition of lysine acetyltransferase 2A activity by small molecule inhibitors suppressed TGF-β and HCC.

Conclusions:
Our study has revealed a novel mechanism by which a metabolic enzyme in tumor cells epigenetically modulates TGF-β signaling, thereby enabling cancer cells to evade immune surveillance and affect their response to immunotherapy.
Outcomes of selective non-operative management in adults with abdominal gunshot wounds: A systematic review and meta-analysis
Authors: Liu Tingwei , Fang Xiaohui , Bai Zhaohui , Liu Lu , Lu Hui , Qi Xingshun 
Published: December 2023

Background and Aims:
Abdominal gunshot wounds (GSWs), a clinically devastating injury, can result in a variety of severe and lethal complications. Traditionally, exploratory laparotomy is the first-line approach for the management of abdominal GSWs, but associated with a considerable amount of unnecessary surgeries. At present, selective non-operative management (SNOM) of abdominal GSWs is becoming an effective and well-recognized approach, but remains widely disputed since many surgeons are skeptical about the validity of SNOM in clinical practice. This meta-analysis aims to estimate the outcomes of SNOM and immediate laparotomy in patients with GSWs by collecting the currently available evidence.

Methods:
The PubMed, EMBASE, and Cochrane Library databases were searched. A random-effects model was employed. Pooled proportion with 95% confidence intervals (CIs) was calculated. Heterogeneity was evaluated using the Cochran’s Q test and I2 statistics.

Results:
Overall, 53 studies involving 60,291 participants were included. The pooled proportions of SNOM and SNOM failure were 27.0% (95%CI=24.0%-30.0%) and 10.0% (95%CI=7.0%-13.0%), respectively. The pooled mortality after SNOM and SNOM failure were 0.0% (95%CI=0.0%-1.0%) and 0.0% (95%CI=0.0%-0.0%), respectively. The pooled proportions of immediate laparotomy and unnecessary immediate laparotomy were 73.0% (95%CI=70.0%-76.0%) and 10.0% (95%CI=8.0%-13.0%), respectively. The pooled mortality after immediate laparotomy and unnecessary immediate laparotomy were 10.0% (95%CI=8.0%-13.0%) and 0.0% (95%CI=0.0%-1.0%), respectively. Heterogeneity was statistically significant in nearly all meta-analyses.

Conclusion:
Immediate laparotomy is still the mainstay approach for the management of abdominal GSWs. Approximately one third of patients with abdominal GSWs undergo SNOM. SNOM failure is not frequent and its related mortality is also rare.
A Case of Metastatic Renal Cell Carcinoma to the Maxillary Sinus Initially Presenting as Recurrent Epistaxis
Authors: Mehr Justin P. , Blum Kyle A. , Jones William S. , Maithel Neha , Citardi Martin J. , Canfield Steven 
Published: December 2023

Abstract
Metastatic neoplasms to the sinonasal tract are rare. Here, we report the case of a 74-year-old woman with no notable oncological history, presenting to the emergency department with a 3-week history of intermittent epistaxis. CT and MRI revealed a right-sided sinonasal tract mass with histopathological analysis revealing cells of clear cell renal cell carcinoma origin. Full-body CT revealed a 4.9-cm L renal mass for which cytoreductive nephrectomy was performed after immunotherapy. The patient experienced recurrence of the sinonasal mass 14 months from initial discovery, for which they continue to follow with our multidisciplinary cancer care team.
Utilization of Instagram by Urology Residency Programs for Applicant Recruitment
Authors: Li Oscar , Grutman Aurora , Rabinowitz Matthew , Clifton Marisa 
Published: December 2023

Purpose:
To assess Instagram content and trends by urology residency programs.

Materials and Methods:
A cross-sectional analysis of urology residency program Instagram accounts was completed after data collection between October 1 and 20, 2022. Included accounts were reviewed and descriptive details were recorded, such as number of followers, those followed, and post content. All posts were then coded on a predetermined list of 7 categories: (1) resident promotion; (2) faculty/departmental promotion; (3) activities outside medicine; (4) research, presentation, or awards; (5) urology match/application-related promotion; (6) “urology in general”; and (7) other.

Results:
Overall, 66 of 147 (44.9%) programs had an account at the time of analysis. About half (31 of 66, 47%) of accounts were created between June and December 2020. Accounts had a median of 633 followers (IQR: 254,844) and 39 posts (IQR: 18,64). Of the 3236 posts analyzed, the majority featured residents or activities outside medicine; video posts were least used. Posts promoting residents had significantly higher average likes per post compared with all other categories except posts about “urology in general.”

Conclusions:
To our knowledge, this is the first study analyzing the use of Instagram by urology residency programs for recruitment. Our study describes an increasing number of urology residency program Instagram accounts for showcasing residents and life outside of medicine to engage with followers.
The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy
Authors: Jacobson Jeffrey M. , Felber Barbara K. , Chen Huichao , Pavlakis George N. , Mullins James I. , De Rosa Stephen C. , Kuritzkes Daniel R. , Tomaras Georgia D. , Kinslow Jennifer , Bao Yajing , Olefsky Maxine , Rosati Margherita , Bear Jenifer , Heptinstall Jack R. , Zhang Lu , Sawant Sheetal , Hannaman Drew , Laird Gregory M. , Cyktor Joshua C. , Heath Sonya L. , Collier Ann C. , Koletar Susan L. , Taiwo Babafemi O. , Tebas Pablo , Wohl David A. , Belaunzaran-Zamudio Pablo F. , McElrath M. Juliana , Landay Alan L. ,   ACTG 5369 Study Team
Published: December 2023

Objective:
The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).

Design:
AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+ T-cell counts greater than 500 cells/μl, and nadir CD4+ T-cell counts greater than 350 cells/μl.

Methods:
The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.

Results:
There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+ and/or CD8+ T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.

Conclusion:
A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.
Promising developments in gonococcal vaccines
Authors: Waltmann Andreea , Chen Jane S. , Duncan Joseph A. 
Published: December 2023

Purpose of review
While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades. This review highlights recent progress in the field.

Recent findings
Vaccines containing outer-membrane vesicles (OMV) have been used to manage outbreaks of the serogroup B N. meningitidis in a number of countries. Epidemiologic studies indicate these vaccination campaigns were associated with reductions in reported N. gonorrhoeae infections. Recently, a serogroup B N. meningitidis vaccine containing both recombinant antigens and OMV has been licensed through much of the world. Epidemiologic studies also demonstrate associations between 4CMenB immunization and reduced N. gonorrhoeae infections. Additionally, mathematical modeling studies have begun to identify potential strategies for vaccine deployment to maximize reduction of infections.

Summary
After several decades with little progress towards an effective gonococcal vaccine, large observational studies have provided evidence that a new generation of group B N. meningitidis vaccines containing OMV have serendipitously restarted the field. Ongoing clinical trials will soon provide definitive evidence regarding the efficacy of these vaccines in preventing N. gonorrhoeae infection.
68Ga-PSMA-11 Uptake in a Large Fibroadenoma in a Male Axillary Accessory Breast
Authors: Solanki Ritanshu , Mittal Bhagwant Rai , Kumar Rajender , Singh Harmandeep , Sekar Aravindh , Dahiya Divya 
Published: December 2023

Abstract
Prostate-specific membrane antigen PET imaging has revolutionized the role of prostate cancer diagnosis and management, with very high sensitivity and specificity. To prevent misdiagnosis and for accurate therapy planning, prostate-specific membrane antigen (PSMA) uptake in nonprostatic diseases needs to be recognized correctly. Besides the physiological PSMA expression, 68Ga-PSMA-11 uptake has been mentioned in multiple oncological and nononcological lesions. The present case report exhibits 68Ga-PSMA-11 uptake in fibroadenoma in a male accessory breast in the right axillary region.
Unusual Perineal Metastasis in a Case of Prostate Cancer on 68Ga-PSMA-11 PET/CT
Authors: Solanki Ritanshu , Mittal Bhagwant Rai , Kumar Rajender , Sekar Aravindh , Kumar Narender 
Published: December 2023

Abstract
Prostate cancer is the fifth leading cause of death in the male population worldwide. 68Ga-PSMA PET/CT has proved to be an excellent modality with greater accuracy for nodal and bone/visceral metastases staging than bone scintigraphy and CT scan, with high sensitivity and specificity. Common sites of metastasis include bone (84%), lymph nodes (10.6%), liver (10.2%), lung, and pleura (9.1%); however, metastasis to the skin is quite rare (≤0.36%). The present case demonstrates PSMA-avid perineal metastasis in a patient of prostate cancer postchemoradiotherapy on 68Ga-PSMA PET/CT scan.
Folic acid prevents interferon-induced iron accumulation and ferroptosis and improves liver health in children with biliary atresia
Authors: Xu Yanhui , Chen Xixi , Fang Rongli , Ning Yu , Zhu Zhijun , Wang Xiaolei , Xiao Yunnan , Li Xiaotian , Ren Huifang , Zhang Yanfang , Zuo Xiaoyu , Chai Chengwei , Zhong Kanghua , Liang Jiankun , Liang Qifeng , Luo Yuanyuan , Xu Yi , Liao Kaili , He Qiuming , Tan Xuying , Ye Qingqing , Lin Zefeng , Han Yang , Luo Zhenhua , Gu Xiaoqiong , Zhang Yan , Sun Liying , Bai Fan , Liu Jinbao , Lv Junqiang , Yao Zhi , Lew Andrew M , Xia Huimin , Zhou Wenhao , Wen Zhe , Chen Zhanghua , Zhang Yuxia 
Published: December 2023

AbstractBackground & AimsBiliary atresia (BA) is an obstructive newborn jaundice disease that leads to liver failure in the majority of affected infants. Viral infection is an important environmental trigger of BA. The aim of the study is to establish how viral infection rewires the cellular and metabolic processes of the digestive systems in at-risk infants and leads to BA development.MethodsSingle cell RNA (scRNA) transcriptomes and V(D)J sequences were generated using small intestine and liver biopsies from BA and control infants. Candidate risk genes were identified by genome-wide association study. Patient specimens, mouse model of experimental biliary atresia, and a myeloid-specificFolr2knockout mice (folr2Mko) were used to determine immune pathologies that lead to BA development. An open label clinical trial was conducted to determine the therapeutic effect of folic acid on post-Kasai’s outcomes of patients with BA.ResultsType I interferon (IFN-I) signaling is persistently activated in infants with BA. This promotes expression of hepcidin in hepatic TREM2+macrophages and hepatocytes, which impairs SLC40A1-mediated iron excretion from the small intestine, leading to iron accumulation, lipid peroxidation, dysbiosis and folic acid deficiency. By genetic ablation ofFolr2,we show that folinate supplementation halts persistent IFN-I activation and suppresses hepcidin expression by TREM2+macrophages. In an open label clinical study, folic acid supplementation decreased post-Kasai’s cholangitis incidences and liver transplantation rates by 70%.ConclusionPersistent IFN-I signaling plays a critical role in virally induced pathological jaundice in infants, and that folic acid supplementation is an effective therapy for BA.
GPT-4 and Neurologists in Screening for Mild Cognitive Impairment in the Elderly: A Comparative Analysis Study
Authors: Yang Hao , Wang Ruihan , Wang Changyu , Gao Hui , Cai Hanlin , Zhang Fengying , Liu Jialin , Liu Siru 
Published: December 2023

SummaryThis study evaluates the efficacy of GPT-4 in screening for Mild Cognitive Impairment (MCI) in the elderly, comparing it with junior neurologists. MCI is a precursor to dementia, presenting a significant public health concern due to the rising global aging population. With over 55 million people affected by dementia worldwide, early detection is essential for timely intervention. Common screening tools, while effective, are resource-intensive, highlighting the need for more efficient methods. The study used an exploratory design with 174 participants, comparing the performance of GPT-4 against three junior neurologists. The GPT-4 model was trained using a set of language analysis indicators to evaluate the severity of MCI. Participants’ test texts and voices were grouped and independently assessed by the neurologists and the GPT-4 model. The neurologists and the GPT-4 model independently assessed the participants’ test corpus. The neurologists assessed both the text and voice of the test, while the GPT model assessed the text only. Results showed that the GPT-4 model had higher accuracy (0.81) compared to the neurologists (ranging from 0.41 to 0.49). GPT-4 demonstrated better discrimination of MCI with significant statistical difference (p < 0.001). The study also developed a clinical risk assessment nomogram based on the top ten weighted features from GPT-4’s analysis, aiding in MCI patient evaluation. In conclusion, the GPT-4 model shows promise as a diagnostic aid for MCI, potentially improving patient outcomes and reducing healthcare burdens. However, its practical applicability in real-world scenarios requires further investigation and clinical validation.
Instagram as a health education tool: Evaluating the efficacy and quality of medical content on Instagram in Azerbaijan
Authors: Graefen Bahar , Hasanli Shams , Jabrayilov Araz , Alakbarova Gulgaz , Tahmazi Khayala , Gurbanova Jamila , Fazal Nadeem 
Published: December 2023

AbstractBackgroundIn recent years, Instagram has become the most popular tool among professional doctors in Azerbaijan for educating their patients. The use of the Instagram application aims to raise patients’ awareness of the importance of taking care of their health and to increase their knowledge about their health conditions using modern services. In this article, the authors examine the quality of Instagram content for health education among the population.MethodsWe conducted a survey to collect anonymous data from more than 205 respondents and summarized the following points.Results65% of the respondents were already obtaining health information from Instagram before to participating in the study. 15.1 % of them frequently visit Instagram for health information while 5% had found the health information accessed there harmful. 71% of respondents think accessing health information in this way is beneficial but that the quality and usefulness of the content is average. 95% of respondents reported that the health information they obtained from the identical platform was not causing them any harmConclusionThe medical information shared on Instagram is generally considered useful and beneficial by the population, but it is desirable to improve the quality of the content.
On the dependence of the critical success index (CSI) on prevalence
Authors: Mbizvo Gashirai K. , Larner Andrew J. 
Published: December 2023

AbstractRecently the critical success index (CSI) has been increasingly discussed and advocated as a unitary outcome measure in various clinical situations where large numbers of true negatives may influence the interpretation of other more traditional outcome measures such as sensitivity and specificity, or when unified interpretation of positive predictive value (PPV) and sensitivity (Sens) is needed. The derivation of CSI from measures including PPV has prompted questions as to whether and how CSI values may vary with disease prevalence (P), just as PPV estimates are dependent on P, and hence whether CSI values are generalizable between studies with differing prevalences. As no detailed study of the relation of CSI to prevalence has been undertaken hitherto, the dataset of a previously published test accuracy study of a cognitive screening instrument was reinterrogated to address this question. Three different methods were used to examine the change in CSI across a range of prevalences, using both Bayes formula and equations directly relating CSI to Sens, PPV, P, and to test threshold (Q). These approaches showed that, as expected, CSI does vary with prevalence, but the dependence differs according to the method of calculation adopted. Bayesian rescaling both Sens and PPV generates a concave curve, suggesting that CSI will be maximal at a particular prevalence which may vary according to the particular dataset.
Imaging neuronal voltage beyond the scattering limit
Authors: Chen Tsai-Wen , Huang Xian-Bin , Plutkis Sarah E. , Holland Katie L. , Lavis Luke D. , Lin Bei-Jung 
Published: December 2023

AbstractVoltage imaging is a promising technique for high-speed recording of neuronal population activity. However, tissue scattering severely limits its application in dense neuronal populations. Here, we adopted the principle of localization microscopy, a technique that enables super-resolution imaging of single-molecules, to resolve dense neuronal activitiesin vivo. Leveraging the sparse activation of neurons during action potentials (APs), we precisely localize the fluorescence change associated with each AP, creating a super-resolution image of neuronal activities. This approach, termedActivityLocalizationImaging (ALI), identifies overlapping neurons and separates their activities with over 10-fold greater precision than what tissue scattering permits. Using ALI, we simultaneously recorded over a hundred densely-labeled CA1 neurons, creating a map of hippocampal theta oscillation at single-cell and single-cycle resolution.