bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer
Authors: Juarez Tiffany M , Gill Jaya M , Heng Annie , Carrillo Jose A , Wagle Naveed , Nomura Natsuko , Nguyen Minhdan , Truong Judy , Dobrawa Lucia , Sivakumar Walavan , Barkhoudarian Garni , Kelly Daniel F , Kesari Santosh
Published: March 2024

Background

Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers.

Methods

Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity.

Results

A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%).

Conclusions

Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.
Welfare-maximizing patent length in a dynamic general equilibrium model
Authors: Iwaisako Tatsuro
Published: March 2024

This article examines analytically the welfare-maximizing patent length in a dynamic general equilibrium model which is based on a variety expansion R&D-based growth model. The results show that if the elasticity of substitution among the intermediate goods is higher, that is, the price elasticity of demand is higher, the welfare-maximizing patent length is shorter. This article also examines the welfare-maximizing mix of patent length and breadth, and numerically obtains similar results, that is, a higher elasticity of substitution shortens the welfare-maximizing length.
Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels
Authors: Handley Guy , Greene John , Cannella Anthony P , Velez Ana Paula , Shah Shivan , Pasikhova Yanina
Published: March 2024

Background

Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation.

Methods

In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL.

Results

Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated.

Conclusions

A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.
Sacraments of the Law: Discovering Common Ground of Law and Religion
Authors: Hahn Judith
Published: March 2024

This article proposes to identify ritualization—as the differentiation between the profane and the sacred—as the basic act underlying the creation of norms. In this light, we can perceive ritualization as a common ground of law and religion. This is particularly evident in ‘sacraments’, a specific type of ritual that culminates in the realization of the sacred within the profane. As ‘norm-facts’, sacraments draw the sacred into our everyday world. This connection has been evident since Roman times when ‘sacraments’ denoted performative signs of a juridico-religious nature. If one acknowledges that both religion and law draw not merely on essential ritual processes of generating normative meaning, but also use sacramental action to realize sacred norms within profane contexts, speaking of ‘law and religion’ reaches deeper than identifying the common topics of two separate spheres of the social. We have then in fact discovered an elemental and common foundation of law and religion.
Long-Term Consequences of PTI Activation and Its Manipulation by Root-Associated Microbiota
Authors: Nakano Ryohei Thomas , Shimasaki Tomohisa
Published: March 2024

In nature, plants are constantly colonized by a massive diversity of microbes engaged in mutualistic, pathogenic or commensal relationships with the host. Molecular patterns present in these microbes activate pattern-triggered immunity (PTI), which detects microbes in the apoplast or at the tissue surface. Whether and how PTI distinguishes among soil-borne pathogens, opportunistic pathogens, and commensal microbes within the soil microbiota remains unclear. PTI is a multimodal series of molecular events initiated by pattern perception, such as Ca2+ influx, reactive oxygen burst, and extensive transcriptional and metabolic reprogramming. These short-term responses may manifest within minutes to hours, while the long-term consequences of chronic PTI activation persist for days to weeks. Chronic activation of PTI is detrimental to plant growth, so plants need to coordinate growth and defense depending on the surrounding biotic and abiotic environments. Recent studies have demonstrated that root-associated commensal microbes can activate or suppress immune responses to variable extents, clearly pointing to the role of PTI in root–microbiota interactions. However, the molecular mechanisms by which root commensals interfere with root immunity and root immunity modulates microbial behavior remain largely elusive. Here, with a focus on the difference between short-term and long-term PTI responses, we summarize what is known about microbial interference with host PTI, especially in the context of root microbiota. We emphasize some missing pieces that remain to be characterized to promote the ultimate understanding of the role of plant immunity in root–microbiota interactions.
Exceeding the limit for microscopic image translation with a deep learning-based unified framework
Authors: Dai Weixing , Wong Ivy H M , Wong Terence T W
Published: March 2024

Deep learning algorithms have been widely used in microscopic image translation. The corresponding data-driven models can be trained by supervised or unsupervised learning depending on the availability of paired data. However, general cases are where the data are only roughly paired such that supervised learning could be invalid due to data unalignment, and unsupervised learning would be less ideal as the roughly paired information is not utilized. In this work, we propose a unified framework (U-Frame) that unifies supervised and unsupervised learning by introducing a tolerance size that can be adjusted automatically according to the degree of data misalignment. Together with the implementation of a global sampling rule, we demonstrate that U-Frame consistently outperforms both supervised and unsupervised learning in all levels of data misalignments (even for perfectly aligned image pairs) in a myriad of image translation applications, including pseudo-optical sectioning, virtual histological staining (with clinical evaluations for cancer diagnosis), improvement of signal-to-noise ratio or resolution, and prediction of fluorescent labels, potentially serving as new standard for image translation.
Leakage of old carbon dioxide from a major river system in the Canadian Arctic
Authors: Dasari Sanjeev , Garnett Mark H , Hilton Robert G
Published: March 2024

The Canadian Arctic is warming at an unprecedented rate. Warming-induced permafrost thaw can lead to mobilization of aged carbon from stores in soils and rocks. Tracking the carbon pools supplied to surrounding river networks provides insight on pathways and processes of greenhouse gas release. Here, we investigated the dual-carbon isotopic characteristics of the dissolved inorganic carbon (DIC) pool in the main stem and tributaries of the Mackenzie River system. The radiocarbon (14C) activity of DIC shows export of “old” carbon (2,380 ± 1,040 14C years BP on average) occurred during summer in sampling years. The stable isotope composition of river DIC implicates degassing of aged carbon as CO2 from riverine tributaries during transport to the delta; however, information on potential drivers and fluxes are still lacking. Accounting for stable isotope fractionation during CO2 loss, we show that a large proportion of this aged carbon (60 ± 10%) may have been sourced from biospheric organic carbon oxidation, with other inputs from carbonate weathering pathways and atmospheric exchange. The findings highlight hydrologically connected waters as viable pathways for mobilization of aged carbon pools from Arctic permafrost soils.
Systemic sclerosis-associated pulmonary arterial hypertension is characterized by a distinct peripheral T helper cell profile
Authors: Papadimitriou Theodoros Ioannis , Lemmers Jacqueline M J , van Caam Arjan P M , Vos Jacqueline L , Vitters Elly L , Stinissen Lizan , van Leuven Sander I , Koenders Marije I , van der Kraan P M , Koenen Hans J P M , Smeets Ruben L , Nijveldt Robin , Vonk Madelon C , Thurlings Rogier M
Published: March 2024

Objectives

Systemic sclerosis (SSc) is characterized by multiple clinical manifestations. Vasculopathy is a main disease hallmark and ranges in severity from an exacerbated Raynaud phenomenon to pulmonary arterial hypertension (PAH). The potential involvement of the immune system in SSc-associated vascular abnormalities is not clear. Here, we set out to study SSc-related immune parameters and determine whether and which peripheral T cell subsets associate with vascular severity in SSc patients.

Methods

Peripheral blood and clinical data were collected from 30 SSc patients, 5 patients with idiopathic PAH and 15 age and sex-matched healthy donors (HD). In this cross-sectional cohort, SSc patients with PAH (n = 15) were matched for their age, sex and medication with SSc patients with no signs of PAH (n = 15). Lymphocyte subsets were quantified by multi-colour flow cytometry.

Results

SSc patients exhibited elevated percentages of T peripheral helper cells (Tph), CD4+GZMB+ T cells and decreased levels of Th1 cells compared with HD. Increased presence of both CD4+ and CD8+ exhausted-like (CD28−) T cells, characterized by raised cytokine and cytotoxic signature, was also observed in SSc compared with HD blood. Furthermore, IL-4 expressing CD4+CD8+ T cells were significantly increased in SSc peripheral blood. Interestingly, the presence of PAH in SSc was accompanied by a distinct T helper profile, characterized by raised percentages of Th17 and Tph cells.

Conclusion

SSc patients with severe vasculopathy (presence of PAH) exhibited a distinct T cell profile, suggesting a potential role of auto-immune inflammation in SSc vascular complications.
Risk of diabetes mellitus in systemic lupus erythematosus: systematic review and meta-analysis
Authors: Etchegaray-Morales Ivet , Mendoza-Pinto Claudia , Munguía-Realpozo Pamela , Solis-Poblano Juan Carlos , Méndez-Martínez Socorro , Ayón-Aguilar Jorge , Abud-Mendoza Carlos , García-Carrasco Mario , Cervera Ricard
Published: March 2024

Objective

To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE.

Methods

Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774).

Results

A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87–1.27; P = 0.63 and RR = 1.32, 95% CI 0.93–1.87; P = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients.

Conclusion

Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk.
JMJD3 activation contributes to renal protection and regeneration following acute kidney injury in mice
Authors: Yu Chao , Tang Jinhua , Yu Jianjun , Wang Yanjin , Liu Na , Dong Zheng , Zhuang Shougang
Published: March 2024

We have recently demonstrated that Jumonji domain‐containing protein D3 (JMJD3), a histone demethylase of histone H3 on lysine 27 (H3K27me3), is protective against renal fibrosis, but its role in acute kidney injury (AKI) remains unexplored. Here, we report that JMJD3 activity is required for renal protection and regeneration in murine models of AKI induced by ischemia/reperfusion (I/R) and folic acid (FA). Injury to the kidney upregulated JMJD3 expression and induced expression of H3K27me3, which was coincident with renal dysfunction, renal tubular cell injury/apoptosis, and proliferation. Blocking JMJD3 activity by GSKJ4 led to worsening renal dysfunction and pathological changes by aggravating tubular epithelial cell injury and apoptosis in both murine models of AKI. JMJD3 inhibition by GSKJ4 also reduced renal tubular cell proliferation and suppressed expression of cyclin E and phosphorylation of CDK2, but increased p21 expression in the injured kidney. Furthermore, inactivation of JMJD3 enhanced I/R‐ or FA‐induced expression of TGF‐β1, vimentin, and Snail, phosphorylation of Smad3, STAT3, and NF‐κB, and increased renal infiltration by F4/80 (+) macrophages. Finally, GSKJ4 treatment caused further downregulation of Klotho, BMP‐7, Smad7, and E‐cadherin, all of which are associated with renal protection and have anti‐fibrotic effects. Therefore, these data provide strong evidence that JMJD3 activation contributes to renal tubular epithelial cell survival and regeneration after AKI.
Clinical Efficacy of Beta-1 Selective Beta-Blockers Versus Propranolol in Patients With Thyroid Storm: A Retrospective Cohort Study*
Authors: Matsuo Yuichiro , Jo Taisuke , Watanabe Hideaki , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: March 2024

OBJECTIVES:

Thyroid storm is the most severe manifestation of thyrotoxicosis. Beta-blockers are among the standard treatment regimens for this condition, with propranolol being the historically preferred option. However, 2016 guidelines issued by the Japan Thyroid Association and the Japan Endocrine Society recommend the use of beta-1 selective beta-blockers over nonselective beta-blockers, such as propranolol. Nevertheless, evidence supporting this recommendation is limited. Herein, we aimed to investigate the in-hospital mortality of patients with thyroid storms based on the choice of beta-blockers.

DESIGN:

Retrospective cohort study.

SETTING:

The Diagnosis Procedure Combination database, a national inpatient database in Japan.

PATIENTS:

Patients hospitalized with thyroid storm between April 2010 and March 2022.

INTERVENTIONS:

Propensity-score overlap weighting was performed to compare in-hospital mortality between patients who received beta-1 selective beta-blockers and those who received propranolol. Subgroup analysis was also conducted, considering the presence or absence of acute heart failure.

MEASUREMENTS AND MAIN RESULTS:

Among the 2462 eligible patients, 1452 received beta-1 selective beta-blockers and 1010 received propranolol. The crude in-hospital mortality rates were 9.3% for the beta-1 selective beta-blocker group and 6.2% for the propranolol group. After adjusting for baseline variables, the use of beta-1 selective beta-blockers was not associated with lower in-hospital mortality (6.3% vs. 7.4%; odds ratio, 0.85; 95% CI, 0.57–1.26). Furthermore, no significant difference in in-hospital mortality was observed in patients with acute heart failure.

CONCLUSIONS:

In patients with thyroid storm, the choice between beta-1 selective beta-blockers and propranolol did not affect in-hospital mortality, regardless of the presence of acute heart failure. Therefore, both beta-1 selective beta-blockers and propranolol can be regarded as viable treatment options for beta-blocker therapy in cases of thyroid storm, contingent upon the clinical context.
A Quality Improvement Initiative for Detection of Attention-Deficit/Hyperactivity Disorder in an Urban, Academic Safety Net Hospital
Authors: Roberts Mona Doss , Loubeau J. Krystel , Hasan Syeda , Rabin Megan , Sikov Jennifer , Baul Tithi D. , Brigham Rebecca , Gillooly Melissa , Singh Ruby , Cassidy Kaitlin , Spencer Andrea E.
Published: March 2024

Objective:

Improve detection of Attention Deficit/Hyperactivity Disorder (ADHD) in a safety net, hospital-based, academic pediatric practice by optimizing screening with the Pediatric Symptom Checklist attention score (PSC-AS) and further evaluation with the Vanderbilt ADHD Diagnostic Rating Scale (VADRS).

Methods:

We implemented a multi-component intervention by (1) optimizing electronic medical record (EMR) features; (2) adjusting clinic operational workflow; and (3) creating a decision-making algorithm for pediatric primary care clinicians (PPCCs). We extracted 4 outcomes manually from the EMR (pediatrician acknowledgment of a positive PSC-AS, documentation of a plan for further evaluation, distribution of VADRS, and completion of at least 1 VADRS). Outcomes were measured monthly in run charts compared to the pre-intervention control period, and implementation was optimized with Plan-Do-Study-Act cycles.

Results:

PPCCs were significantly more likely to acknowledge a positive PSC-AS in the intervention versus control (65.3% vs 41.5%; p < 0.001), although this did not change documentation of a plan (70% vs 67.1%; p-value = 0.565). Significantly more children with a positive PSC-AS were distributed a parent or teacher VADRS in the intervention versus control (30.6% vs 17.7%; p-value = 0.0059), but the percentage of returned VADRS rating scales did not improve (12.9% vs 9.2%; p-value = 0.269).

Conclusion:

Our ADHD detection quality improvement initiative improved use of the PSC-AS to identify attention problems and distribution of VADRS diagnostic rating scales, but additional interventions are needed to improve the completion of ADHD evaluations in primary care to ensure that children are appropriately identified and offered evidence-based care.
A natural language processing algorithm accurately classifies steatotic liver disease pathology to estimate the risk of cirrhosis
Authors: Sherman Marc S. , Challa Prasanna K. , Przybyszewski Eric M. , Wilechansky Robert M. , Uche-Anya Eugenia N. , Ott Ashley T. , McGoldrick Jessica , Goessling Wolfram , Khalili Hamed , Simon Tracey G.
Published: March 2024

Background:

Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction–associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features.

Methods:

From the Mass General Brigham health care system electronic medical record, we identified all patients (1987–2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates.

Results:

The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72–1.5) for metabolic dysfunction–associated steatohepatitis (MASH)/F0, 1.19 (0.92–1.54) for MASH/F1, 1.89 (1.41–2.52) for MASH/F2, and 4.21 (3.26–5.43) for MASH/F3.

Conclusions:

The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.
Genetics of liver disease in adults
Authors: Konkwo Chigoziri , Chowdhury Shanin , Vilarinho Silvia
Published: March 2024

Chronic liver disease stands as a significant global health problem with an estimated 2 million annual deaths across the globe. Combining the use of next-generation sequencing technologies with evolving knowledge in the interpretation of genetic variation across the human genome is propelling our understanding, diagnosis, and management of both rare and common liver diseases. Here, we review the contribution of risk and protective alleles to common forms of liver disease, the rising number of monogenic diseases affecting the liver, and the role of somatic genetic variants in the onset and progression of oncological and non-oncological liver diseases. The incorporation of genomic information in the diagnosis and management of patients with liver disease is driving the beginning of a new era of genomics-informed clinical hepatology practice, facilitating personalized medicine, and improving patient care.
Mesenchymal stem/stromal cells armored by FGF21 ameliorate alcohol-induced liver injury through modulating polarization of macrophages
Authors: Huai Qian , Zhu Cheng , Zhang Xu , Dai Hanren , Li Xiaolei , Wang Hua
Published: March 2024

Background:

Alcohol-associated liver disease (ALD) is a major health care challenge worldwide with limited therapeutic options. Although mesenchymal stem/stromal cells (MSCs) represent a newly emerging therapeutic approach to treat ALD, thus far, there have been extensive efforts to try and enhance their efficacy, including genetically engineering MSCs. FGF21, an endocrine stress-responsive hormone, has been shown to regulate energy balance, glucose, and lipid metabolism and to enhance the homing of MSCs toward injured sites. Therefore, the purpose of this study was to investigate whether MSCs that overexpress FGF21 (FGF21-MSCs) improve the therapeutic effect of MSCs in treating ALD.

Methods:

Human umbilical cord-derived MSCs served as the gene delivery vehicle for the FGF21 gene. Human umbilical cord-derived MSCs were transduced with the FGF21 gene using lentiviral vectors to mediate FGF21 overexpression. We utilized both chronic Lieber-DeCarli and Gao-binge models of ethanol-induced liver injury to observe the therapeutic effect of FGF21-MSCs. Liver injury was phenotypically evaluated by performing biochemical methods, histology, and inflammatory cytokine levels.

Results:

Compared with MSCs alone, administration of MSCs overexpressing FGF21(FGF21-MSCs) treatment significantly enhanced the therapeutic effect of ALD in mice, as indicated by the alleviation of liver injury with reduced steatosis, inflammatory infiltration, oxidative stress, and hepatic apoptosis, and the promotion of liver regeneration. Mechanistically, FGF21 could facilitate the immunomodulatory function of MSCs on macrophages by setting metabolic commitment for oxidative phosphorylation, which enables macrophages to exhibit anti-inflammatory inclination.

Conclusions:

Our data elucidate that MSC modification by FGF21 could enhance their therapeutic effect in ALD and may help in the exploration of effective MSCs-based cell therapies for the treatment of ALD.
Bilateral dead bag syndrome
Authors: Nayak Rashmi , Pai H Vijaya , S Shailaja
Published: March 2024

Introduction:

Posterior capsular rupture (PCR) is defined as breach in the continuity of the posterior part of the capsular bag in the human crystalline lens. Dead bag syndrome (DBS), a term coined by Samuel Masket, is a rare late complication of cataract surgery, which may present with spontaneous posterior capsular tear, causing intraocular lens (IOL) decentration or dislocation. It is usually seen in patients who have undergone an uneventful phacoemulsification with in-the-bag posterior chamber IOL implantation many years ago.

Patient and Clinical Findings:

A 73-year-old man presented with reduced vision in the right eye 17 years after an uneventful phacoemulsification and in-the-bag posterior chamber IOL implantation. There was no history of trauma to the eye. On examination, a decentered IOL with an inferior PCR was noted.

Diagnosis, Intervention, and Outcomes:

Decentered IOL was explanted, and a retro-iris–fixated IOL was implanted. Similar findings were noted in the left eye 4 years after the involvement of the right eye. There was no IOL dislocation or decentration. A diagnosis of DBS as the cause of PCR was made. The left eye was managed conservatively, and the patient remains under observation.

Conclusions:

The case described here seems to correspond to bilateral DBS. Physicians should be alert to look for the possibility of development of a similar complication in the other eye.
Pain in the enthesis of levator ani muscle: A novel source of chronic pelvic pain
Authors: Khasanah Nurida , Peng Chih-Wei , Fang Jessica Jay , Rahman Muhammad Nurhadi , Sulistiawan Dedik , Chin Hung-Yen
Published: March 2024

Background:

Managing chronic pelvic pain (CPP) remains a challenge due to its diverse range of causes. A newly identified anatomical entity known as the enthesis of the levator ani muscle (LAM) and its associated disorders might play a role. This paper describes a novel insight into CPP’s origin, aiming to improve accurate diagnosis and treatment.

Methods:

Data were collected from medical records (paper or electronic) retrospectively. The study included 112 patients meeting the criteria, divided into CPP and non-CPP groups. Clinical symptoms, including location of LAM enthesis, referred pain from pain in LAM enthesis, and related lower urinary tract symptoms (LUTSs) were discussed. To identify differences in symptoms between the groups, a Chi-squared test and descriptive analyses were conducted.

Results:

Bimanual examination revealed tender sites in the attachment of the LAM to the pubic bone. LAM enthesis pain presumably caused referred pain in at least 10 areas, primarily in the lower abdominal quadrate (40.2%-47.3%) followed by the inguinal area (8.9%-15.1%). Multiple LUTSs were observed, including urinary frequency (72.3%), urgency (42.9%), nocturia (53.6%), residual urine sensation (64.3%), urinary incontinence (30.3%), painful bladder (34.8%), and weak urine stream (47.9%). Patients in the CPP groups experienced significant residual urine sensation (53.6%) and bearing-down sensation (42%) compared to the non-CPP group.

Conclusion:

Pain in LAM enthesis is a novel cause of pelvic pain and LUTSs that warrants attention for the evaluation and management of CPP.
Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma
Authors: Pravisani Riccardo , De Martino Maria , Mocchegiani Federico , Melandro Fabio , Patrono Damiano , Lauterio Andrea , Di Francesco Fabrizio , Ravaioli Matteo , Zambelli Marco Fabrizio , Bosio Claudio , Dondossola Daniele , Lai Quirino , Zanchetta Matteo , Dingfelder Jule , Toti Luca , Iacomino Alessandro , Nicolae Sermed , Ghinolfi Davide , Romagnoli Renato , De Carlis Luciano , Gruttadauria Salvatore , Cescon Matteo , Colledan Michele , Carraro Amedeo , Caccamo Lucio , Vivarelli Marco , Rossi Massimo , Nadalin Silvio , Gyori Georg , Tisone Giuseppe , Vennarecci Giovanni , Rostved Andreas , De Simone Paolo , Isola Miriam , Baccarani Umberto
Published: March 2024

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center–protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.
Deceased-Donor Kidney Transplant Outcome Prediction Using Artificial Intelligence to Aid Decision-Making in Kidney Allocation
Authors: Ali Hatem , Mohamed Mahmoud , Molnar Miklos Z. , Fülöp Tibor , Burke Bernard , Shroff Arun , Shroff Sunil , Briggs David , Krishnan Nithya
Published: March 2024

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007–2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes.
A de novo PKD1 mutation in a Chinese family with autosomal dominant polycystic kidney disease
Authors: Wei Ting , Zhang Bing , Tang Wei , Li Xin , Shuai Zhuang , Tang Tao , Zhang Yueyang , Deng Lin , Liu Qingsong
Published: March 2024

Background:

PKD1, which has a relatively high mutation rate, is highly polymorphic, and the role of PKD1 is incompletely defined. In the current study, in order to determine the molecular etiology of a family with autosomal dominant polycystic kidney disease, the pathogenicity of an frameshift mutation in the PKD1 gene, c.9484delC, was evaluated.

Methods:

The family clinical data were collected. Whole exome sequencing analysis determined the level of this mutation in the proband’s PKD1, and Sanger sequencing and bioinformatics analysis were performed. SIFT, Polyphen2, and MutationTaster were used to evaluate the conservation of the gene and pathogenicity of the identified mutations. SWISS-MODEL was used to predict and map the protein structure of PKD1 and mutant neonate proteins.

Results:

A novel c.9484delC (p.Arg3162Alafs*154) mutation of the PKD1 gene was identified by whole exome sequencing in the proband, which was confirmed by Sanger sequencing in his sister (II7). The same mutation was not detected in the healthy pedigree members. Random screening of 100 normal and end-stage renal disease patients did not identify the c.9484delC mutation. Bioinformatics analysis suggested that the mutation caused the 3162 nd amino acid substitution of arginine by alanine and a shift in the termination codon. As a result, the protein sequence was shortened from 4302 amino acids to 3314 amino acids, the protein structure was greatly changed, and the PLAT/LH2 domain was destroyed. Clustal analysis indicated that the altered amino acids were highly conserved in mammals.

Conclusion:

A novel mutation in the PKD1 gene has been identified in an affected Chinese family. The mutation is probably responsible for a range of clinical manifestations for which reliable prenatal diagnosis and genetic counseling may be provided.
Music therapy and anxiety: A bibliometric review from 1993 to 2023
Authors: Lun Tingting , Chen Yuecai , Liu Jingcai , Li Li , Yu Jin , Xiang Meng
Published: March 2024

Background:

Music therapy (MT) has received increasing attention from scholars in the efficacy treatment of anxiety symptoms, which is of great significance to human physical and mental health. The visual mapping functionality of CiteSpace and Vosviewer software was applied in this study to assess the status of MT in the treatment of anxiety symptoms.

Methods:

In order to find research on MT and anxiety that were relevant for this research, we searched the Web of Science database. We also utilized CiteSpace and VOSviewer software to examine institutions, journals, authors, publications, and keywords for scientometric and visual analysis.

Results:

Our findings show that since 2009, the field has developed rapidly and publications on MT and anxiety have gradually increased. The journal Complement Therapies In Medicine published the most relevant articles, the Cochrane Database Of Systematic Reviews journal had the highest citation frequency, and the United States had the most publications. The majority of the top academic institutions in the region are found in the United States, with the University of London having the most publications. The evolution of this field was significantly influenced by Gold C., the author with the most publications, and Bradt J., the author with the most co-citations. The topics of anxiety, nursing, cancer, and pain management have been the focus of this research.

Conclusion:

This study has the potential to increase public understanding of MT and anxiety as well as mental health awareness, all of which are crucial for lowering the prevalence of mental diseases.
Triplane technique for breast reconstruction after breast cancer surgery: A case series report
Authors: Yang Xiao-Juan , Wang Wen-Huan , Zou Jie-Ya , Wang Ji , Yang Zhuang-Qing
Published: March 2024

Rationale:

Implant-based breast reconstruction is an important method for post-mastectomy breast reconstruction. Currently, the most commonly used technique is the biplane technique. However, the high rate of postoperative complications, the inability of pockets to accommodate larger implants, and the expensive costs of biological mesh make the development of new surgical methods urgent. The triplane technique for breast reconstruction is an ideal candidate method.

Patient concerns:

The main local symptoms were breast lump, abnormal breast skin, nipple discharge, and abnormal nipple or areola in 24 patients.

Diagnoses:

The study included 24 female patients who underwent breast reconstruction using the triplane technique after radical breast cancer surgery.

Interventions:

The surgical procedure involved measuring the dimensions of the breast, designing the incision, and creating a pocket for the implant using the triplane technique, which includes the pectoralis major muscle, the pectoralis major fascia continuing to the rectus abdominis fascia, and the latissimus dorsa muscle fascia continuing to the rectus abdominis fascia. Postoperative follow-up included regular assessments of pain and evaluation of breast appearance.

Outcomes:

No cases of postoperative infection were observed in all patients. During the 1-year follow-up period after surgery, 5 patients (20.8%) who needed radiotherapy after mastectomy for cancer showed slight darkening of skin flap pigment after using the triplane technique implant. No cases of exposure or infection of the expanders were reported, and 1 patient underwent expander replacement with a permanent prosthesis. All patients expressed satisfaction with the reconstructed breast shape. The 10 patients (41.7%) experiencing postoperative swelling and pain. However, the pain gradually subsided during the postoperative recovery period. No cases of local recurrence or distant metastasis of breast cancer were observed during the 1-year-follow-up period.

Lessons:

The triplane technique for breast reconstruction after breast cancer surgery provides good implant coverage, reduces the risk of complications, and is cost-effective.
A case report of acute renal failure caused by anti-brucellosis treatment
Authors: Miao Yuanyi , Li Xuegang
Published: March 2024

Rationale:

Rifampicin, as a main chemotherapy drug treating brucellosis, is widely used in clinical practice. Rifampicin-associated ARF is not rare, especially in those rifampicin re-exposure patients. However, this was rare complication of severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium, and few studies have reported it.

Patient concerns:

A 59-year-old male presented to our hospital with acute renal failure (ARF) caused by anti-brucellosis treatment with rifampicin (675 mg/day), gentamicin (320 mg/day), and doxycycline (200 mg/day). He had a contrast-enhanced CT of the upper abdomen before the onset of. After stopping rifampicin and undergoing integrated therapy, the patient’s renal function gradually recovered.

Diagnoses:

Considering that the patient had a history of using rifampicin for pulmonary tuberculosis in the past, based on the examination results, the patient was diagnosed with rifampicin-associated ARF.

Interventions:

Symptomatic treatment such as hemodialysis, and anti-brucella treatment with doxycycline and moxifloxacin were given.

Outcomes:

The patient had significant anuric and polyuric periods and acute tubular necrosis is considered. After treatment, his renal function and urine volume returned to normal, and Brucella melitensis was not isolated from blood cultures.

Lessons:

The case reveals that severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium. Misdiagnosis and mistreatment can deteriorate the patient’s condition. Renal function should be closely monitored in the susceptible patients. Early recognition can provide appropriate therapy to patients. If unexplained renal failure during the use of rifampicin, especially in those rifampicin re-exposure patients, rifampicin-associated ARF should be considered.
Risk factors affecting the sleep quality of patients on dialysis: A single-center cross-sectional study
Authors: Peng Yanmei , Huang Huie , Liao Yumei , Diao Yuhan , Lin Chuangpeng , Liu Yan , Xu Chunhua , Gao Min , He Yan , Yang Guang
Published: March 2024

Sleep quality is among the common complication in patients on dialysis and serious affect their health and quality of life; however, other associated risk factors are unclear. This study aimed to investigate the risk factors affecting sleep quality in patients on dialysis. Data were collected from 260 patients who met the inclusion criteria at out hospital from May 2023 to October 2023. Questionnaires were completed by patients, and biochemical indicators were obtained from past medical records. Univariate and multifactor analyses were used to find factors influencing sleep quality in patients on dialysis. Simple linear regression results showed that female, type of kidney primary disease, high systolic blood pressure (SBP), pruritus, pruritus frequency, restless legs syndrome (RLS), anxiety, and depression were associated with poor sleep quality. Blood biochemical parameters showed that low sodium and calcium levels and high ferritin levels were associated with poor sleep quality. Multiple linear regression statistics showed that female, pruritus, RLS, high SBP, depression, and high ferritin levels were associated with poor sleep quality. This study showed that female, chronic nephritis syndrome, high SBP, pruritus, RLS, low mood. and high ferritin levels were associated with poor sleep quality. Future development of individual nursing and targeted therapies is key to improving sleep quality in patients on dialysis.
The association of hypophysitis with immune checkpoint inhibitors use: Gaining insight through the FDA pharmacovigilance database
Authors: Tang Qirui , Han Yaru , Song Min , Peng Jing , Zhang Mei , Ren Xiaolei , Sun Hailing
Published: March 2024

The use of immune checkpoint inhibitor (ICI) marked a revolutionary change in cancer treatment and opened new avenues for cancer therapy, but ICI can also trigger immune-related adverse events (irAEs). Here, we investigated the publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insight into the possible association between immune checkpoint inhibitors and hypophysitis. Data on adverse events (AEs) due to hypophysitisfor nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected from the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, and the signals for hypophysitis associated with the four drugs were examined using the reporting odds ratio (ROR) method. The number of reported hypophysitis events ≥ 3 and the lower limit of the 95% confidence interval (CI) of the ROR > 1 were considered positive for hypophysitis signals. A total of 1252 AE reports of hypophysitis associated with nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected, including 419, 149, 643, and 41 cases, respectively. The RORs of hypophysitis were 289.58 (95% CI 258.49–324.40), 171.74 (95% CI 144.91–203.54), 2248.57 (95% CI 2025.31–2496.45), and 97.29 (95% CI 71.28–132.79), respectively. All four drugs were statistically correlated with the target AE, with the correlation being, in descending order, ipilimumab, nivolumab, pembrolizumab, and atezolizumab. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab have all been associated with hypophysitis, which can negatively impact quality of life, and early recognition and management of immune checkpoint inhibitor-related hypophysitis is critical.
Network pharmacology-based strategy combined with molecular docking to explore the potential mechanism of agarwood against recurrent aphthous stomatitis
Authors: Tao Si-Yu , Zhang Hai-Ou , Yuan Qing , Li Chu-Xing , Guo Xiang , Sunchuri Diwas , Guo Zhu-Ling
Published: March 2024

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.