tbuckley/cabot-search huggingface dataset:
Ocular Manifestations of COVID-19
Authors: Hannah W. Ng, Daniel A.R. Scott, Helen V. Danesh-Meyer, Justine R. Smith, Charles NJ. McGhee, Rachael L. Niederer
Journal: Progress in Retinal and Eye Research (2024)

There is an increasing body of knowledge regarding how COVID-19 may be associated with ocular disease of varying severity and duration. This article discusses the literature on the ocular manifestations associated with COVID-19, including appraisal of the current evidence, suggested mechanisms of action, associated comorbidities and risk factors, timing from initial infection to diagnosis and clinical red flags. The current literature primarily comprises case reports and case series which inevitably lack control groups and evidence to support causality. However, these early data have prompted the development of larger population-based and laboratory studies that are emerging. As new data become available, a better appraisal of the true effects of COVID-19 on the eye will be possible. While the COVID-19 pandemic was officially declared no longer a "global health emergency" by the World Health Organization (WHO) in May 2023, case numbers continue to rise. Reinfection with different variants is predicted to lead to a growing cumulative burden of disease, particularly as more chronic, multi-organ sequelae become apparent with potentially significant ocular implications. COVID-19 ocular manifestations are postulated to be due to three main mechanisms: firstly, there is a dysregulated immune response to the initial infection linked to inflammatory eye disease; secondly, patients with COVID-19 have a greater tendency towards a hypercoagulable state, leading to prothrombotic events; thirdly, patients with severe COVID-19 requiring hospitalisation and are immunosuppressed due to administered corticosteroids or comorbidities such as diabetes mellitus are at an increased risk of secondary infections, including endophthalmitis and rhino-orbital-mucormycosis. Reported ophthalmic associations with COVID-19, therefore, include a range of conditions such as conjunctivitis, scleritis, uveitis, endogenous endophthalmitis, corneal graft rejection, retinal artery and vein occlusion, non-arteritic ischaemic optic neuropathy, glaucoma, neurological and orbital sequelae. With the need to consider telemedicine consultation in view of COVID-19's infectivity, understanding the range of ocular conditions that may present during or following infection is essential to ensure patients are appropriately triaged, with prompt in-person ocular examination for management of potentially sight-threatening and life-threatening diseases.
Intercellular adhesion molecule-1 suppresses TMZ chemosensitivity in acquired TMZ-resistant gliomas by increasing assembly of ABCB1 on the membrane
Authors: Xin Zhang, Yingying Tan, Tao Li, Dashan Tan, Bin Fu, Mengdi Yang, Yaxin Chen, Mengran Cao, Chenyuan Xuan, Qianming Du, Rong Hu, Qing Wang
Journal: Drug Resistance Updates (2024)

Despite aggressive treatment, the recurrence of glioma is an inevitable occurrence, leading to unsatisfactory clinical outcomes. A plausible explanation for this phenomenon is the phenotypic alterations that glioma cells undergo aggressive therapies, such as TMZ-therapy. However, the underlying mechanisms behind these changes are not well understood.
Letter to the Editor: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis
Authors: Kai Kang, Yijun Wu
Journal: Hepatology (2024)

To the editor, Predicting long-term complications of liver cirrhosis is crucial for facilitating early interventions and improving patient outcomes. With great interest, we read the recent study by Guo et al,1 which reported a noninvasive metabolomic state prediction model based on a UK Biobank cohort of 64,005 participants with extensive baseline data and metabolomic profiles. The metabolomic state model exhibited better performance than routine risk scores, such as the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), in both the training and validation cohorts. In addition, the authors developed and validated a nomogram integrating the metabolic state model with other predictors, which demonstrated better performance compared to the independent metabolic state model, APRI, and FIB-4. Here, we express a concern regarding the use of decision curve analysis (DCA) in assessing the clinical usefulness of the nomogram. In Figure 3 of the original paper, the authors exhibited DCA results for nomogram, metabolomic state model, APRI, and FIB-4 in both training and validation cohorts. As depicted in Figure 1, DCA demonstrates the range of threshold probabilities within which clinical decisions based on the model yield greater net benefits.2,3 According to the DCA from the training cohort, although not as effective as the metabolomic state model, decision based on APRI and FIB-4 still provide higher net benefits than "intervention for all" or "intervention for none" within a certain threshold probability ranges. However, in the validation cohort randomly grouped together with the training cohort, neither APRI nor FIB-4 demonstrated improved net benefits and their decision curves nearly overlapped with those of "intervention for all" and "intervention for none." This inconsistency appears unreasonable for such a large cohort, especially since APRI and FIB-4 are recognized predictive biomarkers,4,5 and in Figure 2B of the original paper. APRI and FIB-4 demonstrate modest predictive accuracy in the validation cohort. This observation prompts us to inquire about the data analysis process, seeking to understand the underlying factors better.FIGURE 1: Schematic diagram of the decision curve of a predictive model. Abbreviation: DCA, decision curve analysis.This work represents a significant step toward leveraging metabolic biomarkers for predicting long-term outcomes in patients with liver cirrhosis. Therefore, we encourage the authors to further elucidate the application of DCA to enhance the strength of the evidence, facilitating the broader adoption of the predictive model.
Letter to the Editor: Enhancing the rigor and impact of cholangiocarcinoma research: Addressing key concerns in the PTPN9-FGFR2 interaction study
Authors: Meng Zhu, Mengqi Qu, Shengxia Lv, Jinfang Zhang, Yongsheng Zhang, Fuzhen Pan
Journal: Hepatology (2024)

1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China 2Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China Abbreviation: CCA, cholangiocarcinoma. In this article, Fuzhen Pan and Yongsheng Zhang are co-corresponding authors. Meng Zhu, Mengqi Qu, Shengxia Lv, and Fuzhen Pan are co-first authors, making equal contributions to this paper. Correspondence Fuzhen Pan, Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, China. Email: [email protected] Correspondence Yongsheng Zhang, School of Basic Medical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou 310053, Zhejiang Province, China. Email: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Letter to the Editor: Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline
Authors: Fei Zhang, Jiahe Wang
Journal: Hepatology (2024)

Department of Family Medicine, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning Province, China Correspondence Jiahe Wang, Department of Family Medicine, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning Province, China. Email: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Molecular Endotypes of Idiopathic Pulmonary Fibrosis: A Latent Class Analysis of Two Multicenter Observational Cohorts
Authors: Manoj V Maddali, Andrew R. Moore, Pratik Sinha, Chad A. Newton, John S. Kim, Ayodeji Adegunsoye, Shwu-Fan Ma, Mary E. Strek, Ching-Hsien Chen, Angela L Linderholm, Rachel L Zemans, Bethany B Moore, Paul J Wolters, Fernando J. Martinez, Angela J. Rogers, Rishi Raj, Imre Noth, Justin M. Oldham
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. Although antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF.
<i>Food and Drug Administration v Alliance for Hippocratic Medicine</i>—A Cautious Win for Reproductive Health Care and FDA Authority
Authors: Michele B. Goodwin, Allison M. Whelan, Lawrence O. Gostin
Journal: JAMA (2024)

This Viewpoint discusses the recent US Supreme Court ruling allowing mifepristone—a drug used in medication abortion—to be widely available in the US, summarizes the history of challenges to the availability of mifepristone, and highlights reasons for concerns that remain after the Court’s current ruling.
Gut microbial features and dietary fiber intake predict gut microbiota response to resistant starch supplementation
Authors: Sri Lakshmi Sravani Devarakonda, Dorothy K. Superdock, Jennifer Ren, Lynn M. Johnson, Aura (Alex) P. Loinard-González, Angela C. Poole
Journal: Gut Microbes (2024)

Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a 7-week crossover study with 59 individuals completing the study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and digestible starch, for 10 d each with 5-d washout periods in between. We collected fecal and saliva samples and food records during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase (AMY1) gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of the relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. AMY1-related metrics were not predictive of response to RS. SAA was only predictive of the relative abundance of one ASV after digestible starch supplementation. Interestingly, SCFA concentrations increased the most during digestible starch supplementation. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation because these data can be used to predict changes in specific ASVs and fecal SCFA concentrations. These findings lay a foundation to support the premise that using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.
Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial
Authors: Paul Glue, Colleen Loo, Johnson Fam, Hsien-Yuan Lane, Allan H. Young, Peter Surman, Nick Glozier, Paul Fitzgerald, Dennis Liu, Shanthi Sharma, Jennifer Grunfeld, David Barton, Malcolm Hopwood, Wayne Miles, Mike Williams, Simon Carson, Johnson Fam, Phern-Chern Tor, Hsien-Yuan Lane, Chun-Hsin Chen, Yu-Jui Huang
Journal: Nature Medicine (2024)

Abstract Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1–8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was −6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235 .
Efficacy of hypnotherapy in chronic idiopathic pruritus: a single-arm prospective pilot study
Authors: Clemence Bertold, Pascal Delaunay, Anne-Claire Cathelineau, Madleen Chassang, Thierry Passeron, Philippe Bahadoran
Journal: British Journal of Dermatology (2024)

There is a large unmet need for treatment of chronic idiopathic pruritus. We show that hypnotherapy can relieve pruritus over several months.
Inflammasomes: emerging therapeutic targets in hidradenitis suppurativa?
Authors: Ciara Campbell, Jay M Mayatra, Ashish J Neve, Jean M Fletcher, Daniel G W Johnston
Journal: British Journal of Dermatology (2024)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent inflammatory lesions, which affect skin and hair follicles in intertriginous areas. HS has a multifactorial aetiology resulting in barrier dysfunction associated with aberrant immune activation. There is increased evidence for the role of inflammasomes in the pathophysiology of inflammatory skin diseases, including HS. Inflammasomes are multiprotein complexes activated following exposure to danger signals, including microbial ligands and components of damaged host cells. Inflammasome activation induces many signalling cascades and subsequent cleavage of proinflammatory cytokines - most notably interleukin (IL)-1β - which have a role in HS pathogenesis. Limited immunotherapies are approved for treating moderate-to-severe HS, with variable response rates influenced by disease heterogeneity. Inflammasomes represent attractive targets to suppress multiple inflammatory pathways in HS, including IL-1β and IL-17. This review aims to summarize the role of inflammasomes in HS and to evaluate evidence for inflammasomes as therapeutic targets for HS treatment.
Potassium-Alkali–Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy
Authors: Donna L. Ralph, Darren Ha, Hillmin Lei, Taylor S. Priver, Scotti D. Smith, Brandon E. McFarlin, Seth Schwindt, Drishti Pandya, Hermann Koepsell, Nuria M. Pastor-Soler, Aurelie Edwards, Alicia A. McDonough
Journal: Journal of the American Society of Nephrology (2024)

Key Points A K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing Na + reabsorption. Uninephrectomy-associated proteinuria could be attributed to elevated single-nephron GFR and downregulation of megalin, which reduced fractional protein endocytosis. Background Losing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate the potential benefits of a K + - alkali–enriched diet and the mechanisms underlying proteinuria. Methods Male Sprague Dawley rats were fed either a 2% NaCl+0.95% KCl diet (HNa-LK) or a 0.74% NaCl+3% K + -alkali diet (HK-alk) for 3 weeks before uninephrectomy and then maintained on respective diets for 12 weeks. BP (by tail-cuff), urine, blood, and kidney proteins were analyzed before and after uninephrectomy. Results Before uninephrectomy, HK-alk–fed versus HNa-LK–fed rats exhibited similar BPs and plasma [K + ], [Na + ], but lower proximal (NHE3, sodium bicarbonate cotransporter 1, NaPi2) and higher distal (NCC, ENaC, and pendrin) transporter abundance, a pattern facilitating K + and HCO 3 − secretion. After uninephrectomy, single-nephron GFR increased 50% and Li + clearance doubled with both diets; in HK-alk versus HNa-LK, the increase in BP was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC- α fell, and NCCp increased, consistent with K + conservation. After uninephrectomy, independent of diet, albuminuria increased eight-fold and abundance of endocytic receptors was reduced (megalin by 44%, disabled homolog 2 by 25%–35%) and kidney injury molecule-1 was increased. Conclusions The K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na + transporters and increasing K + -alkali secretion. Furthermore, uninephrectomy-associated proteinuria could be attributed, at least in part, to elevated single-nephron GFR coupled with downregulation of megalin, which reduced fractional protein endocytosis and V max . Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_07_31_ASN0000000000000420.mp3
Stellate ganglion block for visceral pain in elderly patients undergoing video-assisted thoracoscopic lung cancer surgery: a randomized, controlled trial
Authors: Xiao-bing Xiang, Yang-yang Wu, Zheng Fang, Xiao Tang, Ying-li Wu, Jun Zhou, Xin-qi Cheng
Journal: International Journal of Surgery (2024)

Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS).
The prognostic value of visceral pleural infiltration in ≤3cm non-small cell lung cancer presenting with ground glass opacity: An inverse probability of treatment weighting study
Authors: Zhenyu Yang, Yiming Li, Chenglin Guo, Yikai Xing, Chengwu Liu, Jian Zhang, Qiang Pu, Lunxu Liu
Journal: International Journal of Surgery (2024)

Background: Visceral pleural infiltration (VPI) has been identified as an important risk factor in non-small cell lung cancer (NSCLC) for many decades. However, for patients who present with ground glass opacity (GGO), the prognostic value of VPI is still elusive. We aimed to investigate whether the VPI is a significant prognostic factor in surgically resected ≤3 cm stage I NSCLC who presented with GGO. Materials and methods: Patients with primary NSCLC who underwent surgical resection between December 2009 and December 2018 were collected. Stage I tumors that presented as GGO nodule with a tumor size of less than 3 cm were included and divided into two groups based on VPI status (positive and negative). Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional hazards model and Kaplan-Meier method. Results: A total of 2043 patients were included in this study (VPIs were found in 196 patients). After IPTW weighting, all factors between the two groups were balanced. The median follow-up time was 67.3 months. According to the multivariable Cox models, the VPI was not a significant prognostic factor for OS (HR = 2.00, 95% CI, 0.96-4.17; P = 0.063), but was significant for RFS (HR =2.00, 95% CI, 1.12-3.55; P = 0.019). In subgroup analysis, we found VPI was significant for OS (HR=3.17, 95%CI: 1.09-9.26, P =0.035) and RFS (HR=4.07, 95%CI: 1.76-9.40, P =0.001) in patients with a tumor size &gt;1 cm and a consolidation to tumor ratio (CTR) &gt;50%. For patients with a tumor size ≤1 cm or a CTR ≤50%, the VPI was not significant. Conclusions: VPI may be a significant risk factor for GGOs in NSCLC patients with a tumor size &gt;1 cm and a CTR &gt;50%. Further prospective studies conducted across multi-centers with a larger sample size are needed.
Intraoperative fluorescence redefining neurosurgical precision
Authors: Moksada Regmi, Yanni Li, Yingjie Wang, Weihai Liu, Yuwei Dai, Shikun Liu, Ke Ma, Laisan Pan, Jiacheng Gan, Hongyi Liu, Xiuling Zheng, Jun Yang, Jian Wu, Yang Chenlong
Journal: International Journal of Surgery (2024)

Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures must delicately balance tumor removal with the preservation of surrounding tissue. Achieving clear margins is particularly challenging in cases like glioblastoma due to the limitations of traditional white light visualization. These limitations often result in incomplete resections, leading to frequent recurrences, or excessive resection that harms vital neural structures, causing iatrogenic nerve damage which can lead to sensory and functional deficits. Current statistics reveal a 90% recurrence rate for malignant gliomas. Similarly, an 8% incidence of iatrogenic nerve trauma contributes to an estimated 25 million cases of peripheral nerve injury globally each year. These figures underscore the urgent need for improved intraoperative techniques for lesion margin and nerve identification and visualization. Recent advances in neurosurgical imaging, such as fluorescence-guided surgery (FGS), have begun to address these challenges. Fluorescent agents used in FGS illuminate target tissues, although not all do so selectively. Despite the promising results of agents such as 5-aminolevulinic acid and indocyanine green, their applications are mainly limited by issues of sensitivity and specificity. Furthermore, these agents do not effectively address the need for precise nerve visualization. Nerve Peptide 41, a novel systemically administered fluorescent nerve-targeted probe, shows promise in filling this gap. This review assesses the major fluorescent imaging modalities in neurosurgery, highlighting each of their benefits, limitations, and potential.