bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age added to MELD or ACLF predicts survival in patients with alcohol-associated hepatitis declined for liver transplantation
Authors: Rutledge Stephanie M. , Nathani Rohit , Wyatt Brooke E. , Eschbach Erin , Trivedi Parth , Kerznerman Stanley , Chu Lily , Schiano Thomas D. , Kim-Schluger Leona , Florman Sander , Im Gene Y. 
Published: August 2024

Background:
Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision.

Methods:
We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation.

Results:
Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5–1368) days, 58% (119/206) died at a median of 21 (9–124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey’s (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%).

Conclusions:
Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.
The Effect of Breathing and Relaxation Exercises Training on Psychological Well-Being and Sleep Quality in Individuals Diagnosed With Schizophrenia
Authors: Yıldırım Üşenmez Tülay , Kavak Budak Funda 
Published: August 2024

This study was conducted to determine the effect of breathing and relaxation exercises training on psychological well-being and sleep quality in individuals diagnosed with schizophrenia. This study was conducted at a community mental health center between October 2022 and April 2023 as a randomized controlled study with a pretest-posttest control group. The study’s participants were 64 individuals diagnosed with schizophrenia (31 in the experimental group and 33 in the control group). The Descriptive Characteristics Form, the Psychological Well-being Scale, and the Pittsburg Sleep Quality Index were used to collect data. The individuals in the experimental group underwent 6 sessions of breathing and relaxation exercises training in the form of group training, and no training was applied to the individuals in the control group. It was determined that the individuals in the experimental group had an increase in the total mean score of psychological well-being and a decrease in the total mean score of sleep quality after breathing and relaxation exercise training. In addition, a statistically significant difference was found between the posttest psychological well-being and sleep quality total mean scores of the experimental and control groups (P < .05). It can be said that breathing and relaxation exercises training can be used as an effective intervention to increase the psychological well-being and sleep quality of individuals diagnosed with schizophrenia and can be used in addition to pharmacological treatment.
Comparison of reperfusion- and central repair-first strategies for acute type A dissection with mesenteric malperfusion: a single-center retrospective cohort study
Authors: Gao Xia , Chen Yu-Xin , Ma Wei-Guo , Zhang Li , Cui Cong , Wang Ping-Fan , Yuan Yi-Qiang 
Published: August 2024

Background:
We seek to compare the early and late outcomes of reperfusion-first vs. central repair-first strategies in patients with acute type A dissection (ATAAD) complicated by mesenteric malperfusion.

Methods:
Among 68 patients, reperfusion-first strategy with superior mesenteric artery (SMA) stenting was adopted in 31 and central repair-first in 37, based on rupture risk and circulatory compromise, severity, time and mechanisms of mesenteric ischemia. Early and late outcomes were compared between two strategies. Follow-up was 100% at 3.3±1.4 years.

Results:
Mean age was 50.6±11.4 years (59 males, 86.8%). The reperfusion-first group were more likely to have celiac artery involvement (74.2% vs. 48.6%, P=0.033) and peritoneal irritation signs (19.4% vs. 2.7%, P=0.025), while central repair-first group had more tamponade (27% vs. 3.2%, P=0.008). Early mortality was 48.6% (18/37) with central repair-first strategy vs. 19.4% (6/31) in reperfusion-first group (P=0.012). Reperfusion-first patients had fewer gastrointestinal complications (12.9% vs. 54.1%, P<0.001) and respiratory failure (3.2% vs. 24.3%, P=0.017). At 5 years, SMA stent patency was 84%, and survival was significantly higher in reperfusion-first patients (80.6% vs. 45.9%, P=0.009), with similar freedom from adverse events between two groups (74.9% vs. 76.0%, P=0.812). Tamponade [hazard ratio (HR), 3.093; P=0.023], peritoneal irritation signs (HR, 8.559; P=0.006), and lactate (mmol/l) (HR, 1.279; P<0.001) were predictors for all-cause mortality.

Conclusions:
In this series of ATAAD patients with mesenteric malperfusion, the reperfusion-first strategy with SMA stenting significantly reduced the mortality risk and achieved favorable late survival and freedom from adverse events. These results argue favorably for the use of the reperfusion-first strategy in acute type A dissection with mesenteric malperfusion.
A novel surgical risk predictor combining frailty and hypoalbuminemia – a cohort study of 9.8 million patients from the ACS-NSQIP database
Authors: Panayi Adriana C. , Knoedler Samuel , Rühl Jasmin , Friedrich Sarah , Haug Valentin , Kneser Ulrich , Orgill Dennis P. , Hundeshagen Gabriel 
Published: August 2024

Introduction:
The functional decline seen in frail patients is associated with significant morbidity and mortality. The modified frailty index 5 (mFI-5) score is an accepted risk predictor score in surgery. Hypoalbuminemia has been correlated with poor postoperative outcomes.
There exists, however, a gap in the literature regarding the combined assessment of frailty and hypoalbuminemia and the predictive power of this combined assessment. This retrospective cohort study aimed to investigate the association of preoperative albumin and frailty, as assessed with the mFI-5 score, and its ability to predict surgical outcomes.

Methods:
We queried the ACS-NSQIP database (2008–2021) to identify all surgical patients. Perioperative data, including demographics and preoperative laboratory values, including albumin, were collected. The predictive power of the mFI-5 and hypoalbuminemia (Alb) independently and in combination (mFI-5+Alb), was assessed using multivariable linear and logistic regression models 30-day outcomes were assessed including mortality, length of hospital stay, reoperation, medical and surgical complications, and discharge destination.

Results:
A total of 9 782 973 patients were identified, of whom 4 927 520 (50.4%) were nonfrail (mFI=0), 3 266 636 had a frailty score of 1 (33.4%), 1 373 968 a score of 2 (14.0%), 188 821 a score of 3 (1.9%), and 26 006 a score greater or equal to 4 (0.3%). Albumin levels were available for 4 570 473 patients (46.7%), of whom 848 315 (18.6%) had hypoalbuminemia. The combined assessment (mFI-5+Alb) was found to be a more accurate risk predictor than each factor independently for all outcomes. A weak negative correlation between serum albumin levels and mFI scores was established (Spearman R: −0.2; <0.0001).

Conclusions:
Combined assessment of frailty and albumin was the strongest risk predictor. Therefore, for patients undergoing surgery, we recommend consideration of both serum albumin and frailty in order to optimally determine perioperative planning, including multidisciplinary care mobilization and prehabilitation and posthabilitation.
Deficiency of adenosine deaminase 2 (DADA2) presented with bilateral renal subcapsular hematoma: a case report and literature review
Authors: Al-Ghoul Majd , Yazbak Jillan , Rummanneh Israa , Abuhammad Aseel , Khalilia Ali H. , Wahdan Adnan A. M. 
Published: August 2024

Introduction and importance:
Adenosine deaminase 2 (DADA2) deficiency is a monogenic autoinflammatory disease caused by biallelic mutations in the ADA2 gene. Small- and medium-sized vessels may be involved and can cause various clinical symptoms, including features resembling polyarteritis nodosa (PAN). In this article, the authors discuss a unique case of DADA2 disease in which a patient presented with a bilateral renal subcapsular hematoma.

Case presentation:
An 18-year-old female patient with a history of recurrent optic neuritis presented with a sudden onset of right flank pain as well as nausea, vomiting, weight loss, fever, and elevated arterial blood pressure. Comprehensive abdominal imaging revealed the presence of a bilateral renal subcapsular hematoma. A laboratory test revealed a positive ANA, negative C-ANCA and P-ANCA, and high ESR and CRP. This finding indicated the presence of systemic inflammation. The authors considered DADA2 based on the patient’s clinical features and her family’s history of autoimmune diseases. A genetic study of the patient revealed the presence of a homozygous ADA2 mutation at chromosomal position 22:17182609, which confirmed the presence of adenosine deaminase 2 deficiency.

Clinical discussion:
The authors present a rare case of DADA2 disease successfully treated with immunosuppressive therapy. As the authors suspected of having known autoimmune diseases, the patient’s clinical and laboratory results improved with corticosteroids and etanercept treatment, leading to notable remission. Under continuous CT imaging, the subcapsular hematoma shrank significantly over two months, decreasing from 8.3 to 5 cm in size for the right-sided hematoma and completely disappearing for the left-sided hematoma.

Conclusion:
The clinical features of DADA2 may be fatal, but DADA2 may also be curable; therefore, early diagnosis and treatment are essential.
Lung cancer masquerading as COVID-19 in a young non-smoking woman: case report
Authors: Zarrouki S. , Marouf R. 
Published: August 2024

Introduction and importance:
The clinical and radiological similarities between COVID-19 and lung cancer pose diagnostic challenges, particularly in young, non-smoking individuals. Ground glass opacities (GGO) on imaging, often associated with COVID-19, can also indicate lung cancer. Distinguishing between these conditions is crucial but complex, requiring a systematic approach.

Case presentation:
The authors present a case of a 31-year-old non-smoking woman initially suspected of COVID-19 due to cough, dyspnea, and GGO on chest CT. Despite negative RT-PCR and inconclusive bronchial aspiration, symptoms persisted, prompting further investigation. A PET scan revealed hypermetabolic consolidation, leading to a biopsy confirming adenocarcinoma.

Clinical discussion:
Lung cancer can mimic COVID-19 symptoms, complicating diagnosis, especially in young, non-smoking patients. While smoking remains the primary risk factor, lung cancer in non-smokers, particularly young individuals, is increasingly recognized. GGO, commonly associated with COVID-19, should prompt consideration of malignancy, emphasizing the importance of a comprehensive differential diagnosis.

Conclusion:
Early detection of lung cancer in young, non-smoking individuals is vital yet challenging. Clinicians should maintain a high index of suspicion, promptly investigating persistent or worsening symptoms, even in the absence of traditional risk factors. Timely biopsy and intervention are critical for improving outcomes in this population.
Prompt response to rituximab in a patient with resistant polymyositis with complications of dysphagia and dysphonia: a case report
Authors: Habes Yousef Mahmoud Nimer , Mohammad Sadeh Saif Ibraheem , Saada Layth Jamil Mohammad , Mali Ali Jamil Ali , Abdulrazzak Mohammed , Attawna Saed I. Y. 
Published: August 2024

Introduction and importance:
Polymyositis is an inflammatory process, primarily affecting proximal muscles, characterized by elevated muscle enzymes and distinctive electromyography patterns.

Case presentation:
The authors present a case of a 33-year-old male patient experiencing complications of polymyositis, including pharyngeal and laryngeal involvement leading to dysphagia and dysphonia. Steroids and intravenous immunoglobulin (IVIG) therapy proved ineffective. Subsequently, rituximab was administered, resulting in significant improvement in dysphagia, dysphonia, and proximal muscles within 3 days of the initial rituximab dose. Additionally, there was a remarkable decrease in creatine phosphokinase (CPK) levels.

Clinical discussion:
Immune-mediated myopathies (IMM) are rare diseases characterized by muscle inflammation and weakness. This case of probable polymyositis, diagnosed through clinical features and elevated CPK, was complicated by the patient’s lack of response to glucocorticoids and IVIG therapy. Remarkably, rituximab treatment led to rapid improvement in muscle strength and symptoms, highlighting its potential effectiveness in refractory cases of polymyositis.

Conclusions:
Primary treatment for cases of polymyositis typically involves the use of glucocorticoids. However, approximately half of the patients do not respond adequately to corticosteroids alone. Alternatives, in such cases, encompass IVIG therapy and rituximab.
Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy
Authors: Basu Srijani , Običan Sarah G. , Bertaggia Enrico , Staab Hannah , Izquierdo M. Concepcion , Gyamfi-Bannerman Cynthia , Haeusler Rebecca A. 
Published: August 2024

AbstractIntrahepatic cholestasis of pregnancy (ICP) is characterized by elevated plasma bile acid levels. ICP is linked to adverse metabolic outcomes, including a reported increased risk of gestational diabetes. The standard therapeutic approach for managing ICP is treatment with ursodeoxycholic acid (UDCA) and induction of labor prior to 40 weeks of gestation. To investigate bile acid and metabolic parameters after UDCA treatment, we enrolled 12 ICP patients with singleton pregnancies–half with and half without gestational diabetes–and 7 controls. Our study reveals that after UDCA treatment, notwithstanding a reduction in total bile acid and ALT levels, imbalances persist in the cholic acid (CA) to chenodeoxycholic acid (CDCA) ratio in maternal and cord blood plasma. This indicates a continued dysregulation of bile acid metabolism despite therapeutic intervention. Maternal plasma lipid analysis showed a distinct maternal dyslipidemia pattern among ICP patients, marked by elevated cholesterol levels on VLDL particles and heightened triglyceride concentrations on LDL particles, persisting even after UDCA treatment. Cord plasma lipid profiles in ICP patients exhibited elevated triglyceride and free fatty acid levels alongside a tendency toward increased β-hydroxybutyrate. The changes in lipid metabolism in both maternal and cord blood correlated with the high CA/CDCA ratio, but not total bile acid levels or gestational diabetes status. Understanding the imbalances in maternal and cord bile acid and lipid profiles that persist after standard UDCA therapy provides insights for improving management strategies and mitigating the long-term consequences of ICP.News and NoteworthyThis study uncovers that despite ursodeoxycholic acid treatment, intrahepatic cholestasis of pregnancy (ICP) is associated with increases in the ratio of cholic acid to chenodeoxycholic acid in both maternal and cord blood, suggesting ongoing dysregulation of bile acid metabolism. The high cholic to chenodeoxycholic acid ratio is correlated with maternal dyslipidemia and high cord blood lipids. These findings may inform more targeted approaches to managing ICP.
Treatment Outcomes and MRI Features of SUNA: A Systematic Review and Meta-Analysis
Authors: Verma Jay , Khanduja Sneha , Etienne Mill 
Published: August 2024

AbstractBackgroundTrigeminal autonomic cephalalgias (TACs), including short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), are rare but debilitating headaches. The pathophysiology and optimal treatment of SUNA remain poorly defined, compounded by disparities in healthcare access.ObjectivesTo systematically review and analyze the effectiveness of treatment options, clinical outcomes, and brain MRI findings for SUNA, and to identify gaps in the current evidence base.MethodologyFollowing PRISMA guidelines, a systematic search was performed across multiple databases. Data from 20 studies were analyzed, focusing on treatment efficacy, patient demographics, and MRI findings. Meta-analyses were conducted on treatment effectiveness, and bias was assessed using the Newcastle-Ottawa Scale.ResultsAmong 267 patients, the most commonly used treatments were lamotrigine (37.07%) and greater occipital nerve (GON) block (16.85%), showing effectiveness in over 50% of cases. Heterogeneity in lamotrigine effectiveness was high (Cochran’s Q = 63.10, p-value < 0.0001, α = 0.05). Lidocaine was effective for acute attacks (> 80%). Brain MRIs were mostly unremarkable, with some evidence suggesting neurovascular involvement.ConclusionLamotrigine and GON block are effective for SUNA, though treatment responses vary widely. MRI findings often lack abnormalities, suggesting a need for further research into the pathophysiology of SUNA. Larger, high-quality studies are needed to establish standardized treatment protocols and improve patient outcomes.
Covalently linked adenovirus-AAV complexes as a novel platform technology for gene therapy
Authors: Collins Logan Thrasher , Beatty Wandy , Moyo Buhle , Alves-Bezerra Michele , Hurley Ayrea , Lagor William , Bao Gang , Lu Zhi Hong , Curiel David T. 
Published: August 2024

AbstractAdeno-associated virus (AAV) has found immense success as a delivery system for gene therapy, yet the small 4.7 kb packaging capacity of the AAV sharply limits the scope of its application. In addition, high doses of AAV are frequently required to facilitate therapeutic effects, leading to acute toxicity issues. While dual and triple AAV approaches have been developed to mitigate the packaging capacity problem, these necessitate even higher doses to ensure that co-infection occurs at sufficient frequency. To address these challenges, we herein describe a novel delivery system consisting of adenovirus (Ad) covalently linked to multiple adeno-associated virus (AAV) capsids as a new way of more efficiently co-infecting cells with lower overall amounts of AAVs. We utilize the DogTag-DogCatcher (DgT-DgC) molecular glue system to construct our AdAAVs and we demonstrate that these hybrid virus complexes achieve enhanced co-transduction of cultured cells. This technology may eventually broaden the utility of AAV gene delivery by providing an alternative to dual or triple AAV which can be employed at lower dose while reaching higher co-transduction efficiency.
Cyclin C Promotes Pancreatic Development and Suppresses Cancer Initiation Through Maintenance of the Autophagy-Lysosome Pathway
Authors: Hanley Sara E. , Cai Kathy Q. , Willis Stephen D. , Stieg David C. , Klein-Szanto Andres J. , Campbell Kerry S. , Strich Randy 
Published: August 2024

ABSTRACTThe cyclin C (Ccnc)-Cdk8/Cdk19 kinases are components of the Mediator that represses or activates gene transcription. The present study found that Ccnc is required for both steady state and induced autophagic gene transcription in mouse embryonic fibroblasts. In vivo, pancreatic ablation ofCcnc(CcncPanΔ) resulted in phenotypes (islet atrophy, acinar cell damage) also observed in autophagy deficient models. However,CcncPanΔanimals displayed more dramatic phenotypes including earlier death and accelerated acinar ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) precancerous lesion formation when these animals also expressed oncogenicKrasG12D. Consistent with the in vivo results, aKrasG12D;CcncPanΔpancreatic derived cell line displayed reduced autophagy lysosome pathway (ALP) activation. Although autophagy deficient acinar cells undergo Tp53-dependent cell death, histopathology revealed thatKrasG12D;Ccnc-/-(PC) pancreata did not allowing damaged cells to keep dividing. Therefore, Ccnc both supports normal ALP function protecting endocrine and exocrine cell but also kills damaged cells before they become malignant. Finally, the PC cell line displayed reduced proteasome function rendering cells hypersensitive to proteasome inhibitors. This hypersensitivity was also observed in disparateCcnc-/-tumor cell lines or inCcnc+/+tumor cells co-treated with Cdk8/Cdk19 inhibitors. These findings suggest a new avenue to target pancreatic neoplasms by inhibiting cyclin C-Cdk8/Cdk19 proteasome activity.