bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations Between Integration and Patient Experience in Hospital-Based Health Systems: An Exploration of Horizontal and Vertical Forms of Integration
Authors: Torres Jillian S. , Diana Mark L. 
Published: September 2024

Goal:The U.S. hospital sector is experiencing record levels of integration, with more than half of U.S. physicians and nearly three quarters of all hospitals affiliated with one of slightly more than 630 health systems. However, there is growing evidence to suggest that health system integration is associated with more expensive and lower quality care. The goal of this research is to explore the associations between forms of health system integration and hospital patient experience scores.Methods:A cross-section of data for the year 2019 was assembled and analyzed from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient experience survey. Data from theCompendium of US Health Systems, published by the Agency for Healthcare Research and Quality (AHRQ), and the American Hospital Association (AHA) Annual Survey were used to obtain independent variables and hospital-level covariates. A series of multivariable regressions was used to explore the associations between forms of health system integration and hospital patient experience scores across three domains: overall impression of the hospital; experiences with staff; and the hospital environment. Forms of both horizontal integration (i.e., number of hospitals owned by hospital-based health systems) and vertical integration (i.e., physician-hospital integration, nursing home ownership, accountable care organization [ACO] participation, group purchasing, contract management, offering insurance products, and investor ownership) were explored.Principal Findings:Although horizontal integration was not associated with any meaningful differences in patient experience scores, health systems with physician–hospital integration were associated with overall impression scores that were 2 percentage points higher than systems without physician integration. Similarly, contract management and membership in a group purchasing organization were associated with overall impression and environment scores that were 2 to 3 percentage points higher than hospitals that did not engage in those forms of integration. By contrast, investor ownership was associated with a 5% lower score for overall patient experience compared with other forms of ownership.Practical Applications:The findings of this study suggest that hospitals in more vertically integrated systems may have higher patient experience scores than independent hospitals and those that belong exclusively to horizontally integrated systems. Thus, there are elements of vertical integration that could benefit patients and be worth pursuing. Conversely, higher degrees of horizontal integration in the form of multihospital ownership may not be of any benefit to patients and should be pursued with caution.
Severity of Lower Urinary Tract Symptoms Predicts Neurologic Quality of Life in Patients With Multiple Sclerosis
Authors: Kong Lily , Blubaum Aleksandar C. , Blakely Stephen A. , Miravalle Augusto A. , Flynn Brian J. 
Published: September 2024

Introduction:
Lower urinary tract symptoms (LUTSs) are underreported in patients with multiple sclerosis (MS). We aim to define the incidence of LUTSs in patients with MS and their effect on neurologic quality of life.

Materials and Methods:
We identified patients presenting to the neurology clinic for routine follow-up for multiple sclerosis. Each patient responded to validated questionnaires regarding urinary quality of life using the Bladder Control Scale (BLCS) from the Multiple Sclerosis Quality-of-Life Inventory (MSQLI) and overall Quality of Life in Neurological Disorders (NeuroQOL). A retrospective chart review was performed to assess for the presence of lower urinary tract symptoms. Overall neurologic quality of life was measured in the presence and absence of LUTS, and P-values were calculated using the Student t test. A urinary quality-of-life score was correlated with an overall neurologic quality-of-life score using the Spearman rank correlation coefficient.

Results:
The study included 91 patients who completed the validated questionnaires. Of the 91 patients, 85 (93%) described the presence of at least 1 lower urinary tract symptom. The most common symptoms were urgency (84%), frequency (69%), incontinence (54%), and retention (38%). Seventy-two (79%) patients reported that LUTS negatively affected urinary quality of life. The presence of LUTS negatively affected the overall neurologic quality of life. Urinary quality of life was predictive of the overall neurologic quality of life (−0.22, P = .04).

Conclusions:
LUTSs are very common in patients with MS, and they not only significantly affect but also predict the overall neurologic quality of life.
New Insights Into Pharmacology of GABAA Receptor Alpha Subunits–Selective Modulators
Authors: Moraru Miruna Valeria , Stoleru Smaranda , Zugravu Aurelian , Coman Oana Andreia , Fulga Ion 
Published: September 2024

Background:
Benzodiazepines have long held a leading position in medical therapeutics, known for their multiple common therapeutic properties and primarily being prescribed for anxiety and insomnia. However, their lack of specificity and various side effects have led to a reevaluation of their long-term use, resulting in a rapid growth in the literature focusing on targeted therapies.

Areas of Uncertainty:
Despite many efforts, uncertainties persist and there are heterogeneous findings across studies regarding the pharmacological effects attributed to gamma-aminobutyric acid type A (GABAA) receptor subunits. Selective compounds targeting GABAA receptor alpha subunits are currently under active research and definitive conclusions have not been reached yet. Some compounds have not progressed to clinical trials, while others, if advanced, have been halted. These challenges emphasize the difficulty in translating preclinical findings into clinical use.

Data Sources:
A literature review was conducted using the PubMed database, searching for articles discussing GABAA receptor subunits. The search was refined by including only selective compounds with potential anxiolytic and cognitive enhancement properties.

Results:
Findings reveal compounds with promising anxiolytic and antidepressant effects with minimal sedation and absence of tolerance development. Moreover, some compounds show potential in alleviating cognitive dysfunction. There is a broad spectrum of potential therapeutic applications for selective compounds, ranging from neurological disorders such as epilepsy and neuropathic pain to cognitive dysfunction–related conditions. Currently, the leading selective compounds with the most promising results in ongoing clinical trials are basmisanil and darigabat. Basmisanil holds further exploration potential in the treatment of cognitive impairment and related conditions, while darigabat shows progress in the advancement of adjunctive therapy of focal onset seizures and for the treatment of panic disorder, respectively.

Conclusions:
Future drug discovery efforts are encouraged to focus on positive allosteric modulators that selectively target the α2, α3 subunits and negative/positive allosteric modulators that target the α5 subunit of the GABAA receptor. The pursuit of ligands possessing only anxiolytic effects or those enhancing cognition continues to be an important focus for future research, with promising advancements depicted in recent studies.
Prophylactic Mesh-related Reoperations and Mesh-related Problems During Subsequent Relaparotomies: Long-term Results From the PRIMA Trial
Authors: van den Berg Rudolf , van den Dop L. Matthijs , Timmermans Lucas , van den Berg Michiel , Pierik Robert E.G.J.M. , Zwaans Willem A.R. , Reim Daniel , Buijk Steven E. , van Brussel Jerome P. , Lange Johan F. , Jeekel Johannes J. , Tanis Pieter J. 
Published: September 2024

Objective:
This study aimed to evaluate all mesh-related problems during reoperations after mesh-reinforcement 15 years after the start of the PRIMA trial. SUMMARY BACKGROUND DATA Prophylactic mesh reinforcement during closure of a midline laparotomy has proven to reduce the incidence of incisional hernia, especially in high-risk patients, but long-term mesh-related morbidity is largely unknown.

Methods:
Patients receiving a prophylactic onlay or retro-rectus mesh in the PRIMA trial between 2009 and 2012 were included on an as-treated basis from participating centers that made reoperation notes available. Main outcomes were the incidences of complications requiring mesh explantation, mesh-related ileus, and mesh-related problems during laparotomy for other diagnoses.

Methods:
Out of 373 patients randomized to prophylactic mesh reinforcement, 242 were included: 127 with onlay and 115 patients with retrorectus mesh. Median follow-up is 27 months (IQR 12-78). Thirty-four patients underwent reoperation for any reason during entire follow-up, 22 after onlay (17.3%) and 12 after retrorectus mesh (10.4%). Reoperation rate for complications that required mesh explantation was 4/127 (3.1%) after onlay and 0/115 (0%) after retrorectus mesh. Mesh-related ileus occurred in none of the onlay group, and 3/115 (2.6%) in the retrorectus group. During subsequent laparotomies for other primary diagnoses, adhesions to the mesh were noted in 3/10 patients in the onlay group and 1/5 patients in the retro-rectus group. Overall, the mesh was removed in 10/127 (7.9%) in the onlay group and 7/115 (6.1%) patients in the retro-rectus group.

Conclusions:
In high-risk patients receiving a prophylactic mesh during midline laparotomy closure, low incidences of mesh-related complications requiring reoperation and mesh-related problems during unrelated subsequent laparotomies were found, for both the onlay and retrorectus techniques.
Platelet-rich plasma enhances rib fracture strength and callus formation in vivo
Authors: Camarena Adrian , Kang Lillian , Mirando Anthony J. , Augustine Emily , McMillian Najerie S. , Stinson Natasha C. , Agarwal Suresh M. , Becker Matthew L. , Hilton Matthew J. , Fernandez-Moure Joseph S. 
Published: September 2024

BACKGROUND
Rib fractures are a common traumatic injury affecting more than 350,000 patients a year. Early stabilization has shown to be effective in reducing pulmonary complications. Platelet-rich plasma (PRP) is a growth factor–rich blood product known to improve soft tissue and bone healing. We hypothesized that the addition of PRP to a rib fracture site would accelerate callus formation and improve callus strength.

METHODS
Platelet-rich plasma was isolated from pooled Lewis rat blood and quantified. Thirty-two Lewis rats underwent fracture of the sixth rib and were treated with 100 μL PRP (1 × 106 platelets/μL) or saline. At 2 weeks, ribs were harvested and underwent a 3-point bend, x-ray, and microcomputed tomography, and callus sections were stained with 4′,6-diamidino-2-phenylindole and Alcian blue and picrosirius red. At 6 weeks, ribs were harvested and underwent a 3-point bend test, x-ray, microcomputed tomography, and Alcian blue and picrosirius red staining.

RESULTS
At 2 weeks, PRP increased callus diameter (9.3 mm vs. 4.3 mm, p = 0.0002), callus index (4.5 vs. 2.1, p = 0.0002), bone volume/total volume (0.0551 vs. 0.0361, p = 0.0024), cellularization (2,364 vs. 1,196, p < 0.0001), and cartilage (12.12% vs. 3.11%, p = 0.0001) and collagen (6.64% vs. 4.85%, p = 0.0087) content compared with controls. At 6 weeks, PRP increased fracture callus diameter (5.0 mm vs. 4.0 mm, 0.0466), callus index (2.5 vs. 2.0, p = 0.0466), BV/TV (0.0415 vs. 0.0308, p = 0.0358), and higher cartilage (8.21% vs. 3.26%, p < 0.0001) and collagen (37.61% vs. 28.00%, p = 0.0022) content compared with controls. At 6 weeks, PRP samples trended toward improved mechanical characteristics; however, these results did not reach significance (p > 0.05).

CONCLUSION
Rib fractures are a common injury, and accelerated stabilization could improve clinical outcomes. Platelet-rich plasma significantly increased callus size, calcium deposition, and cartilage and collagen content at 2 and 6 weeks and trended toward improved strength and toughness on mechanical analysis at 6 weeks compared with controls, although this did not reach significance. These findings suggest that PRP may be a useful adjunct to accelerate and improve fracture healing in high-risk patients.
Psychotherapies for the treatment of personality disorders: the state of the art
Authors: Emmelkamp Paul M.G. , Meyerbröker Katharina 
Published: September 2024

Purpose of review
To provide an update of systematic reviews, meta-analyses and recent clinical outcome studies for personality disorder (PD) in order to investigate the state of the art of the evidence of psychotherapy for personality disorders

Recent findings
Few outcome studies in patients with Cluster A and Cluster C PD have been conducted, which limits the conclusions which can be drawn. Most recently published research has been conducted with borderline PD. There is limited evidence that dialectical behavior therapy (DBT), mentalization based therapy and schema therapy are more effective than treatment as usual. There is no convincing evidence that long and intensive therapy is more effective than short and less intensive therapy. Drop-out is rather high for patients with borderline PD. Group therapy results in more drop-outs than individual therapy

Summary
There is a clear need of studies evaluating whether psychotherapies developed for PDs are more effective than CBT for patients with Cluster C PD. Given that studies with patients with Cluster B PD suggest that longer treatment of DBT and mentalization-based treatment is not more effective than shorter treatment this needs to be studied with other evidence-based therapies as well. Serious efforts are needed to evaluate therapies for patients with Cluster A PDs.
Self-driving development of perfusion processes for monoclonal antibody production
Authors: Müller Claudio , Vuillemin Thomas , Gadiyar Chethana Janardhana , Bielser Jean-Marc , Souquet Jonathan , Fagnani Alessandro , Sokolov Michael , von Stosch Moritz , Feidl Fabian , Butté Alessandro , Cruz Bournazou Mariano Nicolas 
Published: September 2024

AbstractIt is essential to increase the number of autonomous agents bioprocess development for biopharma innovation to shorten time and resource utilization in the path from product to process. While robotics and machine learning have significantly accelerated drug discovery and initial screening, the later stages of development have seen improvement only in the experimental automation but lack advanced computational tools for experimental planning and execution. For instance, during development of new monoclonal antibodies, the search for optimal upstream conditions (feeding strategy, pH, temperature, media composition, etc.) is often performed in highly advanced high-throughput (HT) mini-bioreactor systems. However, the integration of machine learning tools for experiment design and operation in these systems remains underdeveloped. In this study, we introduce an integrated framework composed by a Bayesian experimental design algorithm, a cognitive digital twin of the cultivation system, and an advanced 24 parallel mini-bioreactor perfusion experimental setup. The result is an autonomous experimental machine capable of 1. embedding existing process knowledge, 2. learning during experimentation, 3. Using information from similar processes, 4. Notifying events in the near future, and 5. Autonomously operating the parallel cultivation setup to reach challenging objectives. As a proof of concept, we present experimental results of 27 days long cultivations operated by an autonomous software agent reaching challenging goals as are increasing the VCV and maximizing the viability of the cultivation up to its end.
Vascular HIF2 signaling prevents cardiomegaly, alveolar congestion and capillary remodeling during chronic hypoxia
Authors: Teresa Albendea-Gomez , Susana Mendoza-Tamajon , Rosana Castro-Mecinas , Beatriz Escobar , Susana Ferreira Rocha , Sonia Urra-Balduz , Angel Nicolas-Avila Jose , Eduardo Oliver , Maria Villalba-Orero , Silvia Martin-Puig 
Published: September 2024

SUMMARYHypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary arterial hypertension (PAH). Endothelial HIF2 signaling mediates pulmonary arterial remodeling and subsequent right ventricular systolic pressure (RVSP) elevation during chronic hypoxia, encouraging novel therapeutic opportunities for PAH based on specific HIF2 inhibitors. Nevertheless, HIF2 relevance beyond the pulmonary endothelium or in the cardiac adaptation to hypoxia remains elusive. Wilms tumor 1 lineage contributes to heart and lung vascular compartments including pericytes, endothelial and smooth muscle cells. Here we describe the response to chronic hypoxia of a novel HIF2 mutant mouse model in the Wt1 lineage (Hif2/Wt1cKO).Hif2/Wt1cKO is protected against pulmonary remodeling and increased RVSP induced by hypoxia, but displays alveolar congestion, inflammation and hemorrhages associated with microvascular instability. Furthermore, lack of HIF2 in the Wt1 lineage leads to cardiomegaly, capillary remodeling, right and left ventricular hypertrophy, systolic dysfunction and left ventricular dilation, suggesting pulmonary-independent cardiac direct roles of HIF2 in hypoxia. These structural defects are partially restored upon reoxygenation, while functional parameters remain altered. Our results suggest that cardiopulmonary HIF2 signaling prevents excessive vascular proliferation during chronic hypoxia and define novel protective roles of HIF2 to warrant stable microvasculature and organ function.
Targeted long-read sequencing as a single assay improves diagnosis of spastic-ataxia disorders
Authors: Rudaks Laura Ivete , Stevanovski Igor , Yeow Dennis , Reis Andre L. M. , Chintalaphani Sanjog R. , Cheong Pak Leng , Gamaarachchi Hasindu , Worgan Lisa , Ahmad Kate , Hayes Michael , Hannaford Andrew , Kim Samuel , Fung Victor S. C. , Halmagyi Michael , Martin Andrew , Manser David , Tchan Michel , Ng Karl , Kennerson Marina L. , Deveson Ira W. , Kumar Kishore Raj 
Published: September 2024

AbstractThe hereditary spastic-ataxia spectrum disorders are a group of rare disabling neurological diseases. The genetic testing process is complex, and often requires multiple different assays to evaluate the many potential causative genes and variant types, including short tandem repeat expansions, single nucleotide variants, insertions/deletions, structural variants and copy number variants. This can be a protracted process and, even after all avenues are exhausted, many individuals do not receive a genetic diagnosis.Aiming to streamline and improve this process, we developed a targeted long-read sequencing strategy with capacity to characterise genetic variation of all types and sizes within 469 disease-associated genes, in a single assay. We applied this to a cohort of 34 individuals with genetically undiagnosed spastic-ataxia spectrum disorders. An additional five individuals with a known genetic diagnosis were included as positive controls.We identified causative pathogenic variants that would be sufficient for genetic diagnosis in 14/34 (41%) unsolved participants. The success rate was 5/11 (45%) in those who were naïve to genetic testing and 9/23 (39%) in those who were undiagnosed after prior genetic testing, completed on a clinical basis. Short tandem repeat expansions inFGF14were the most common cause, present in 7/34 (21%). Two individuals (2/34, 6%) had biallelic pathogenic short tandem repeat expansions inRFC1and one individual had a monoallelic pathogenic short tandem repeat expansion inATXN8OS/ATXN8. Causative pathogenic sequence variants other than short tandem repeat expansions were found in four individuals, including a heterozygous missense variant inVCP, a heterozygous in-frame deletion inSTUB1, a homozygous splicing variant inANO10, and compound heterozygous missense and nonsense variants inSPG7. In addition to these solved cases, a pathogenic or likely-pathogenic variant with uncertain clinical implications was identified in a further three individuals, including a single individual who was found to have a short tandem repeat expansion inBEAN1in addition to biallelic expansions inFGF14within the range of 200-249 repeats.Our results demonstrate the utility of targeted long-read sequencing in the genetic evaluation of patients with spastic-ataxia spectrum disorders, highlighting both the capacity to increase overall diagnostic yield and to streamline the testing pathway by capturing all known genetic causes in a single assay.
Performance of Open-Source LLMs in Challenging Radiological Cases – A Benchmark Study on 1,933 Eurorad Case Reports
Authors: Kim Su Hwan , Schramm Severin , Adams Lisa C. , Braren Rickmer , Bressem Keno K. , Keicher Matthias , Zimmer Claus , Hedderich Dennis M. , Wiestler Benedikt 
Published: September 2024

AbstractRecent advancements in large language models (LLMs) have created new ways to support radiological diagnostics. While both open-source and proprietary LLMs can address privacy concerns through local or cloud deployment, open-source models provide advantages in continuity of access, and potentially lower costs. In this study, we evaluated the diagnostic performance of eleven state-of-the-art open-source LLMs using clinical and imaging descriptions from 1,933 case reports in the Eurorad library. LLMs provided differential diagnoses based on clinical history and imaging findings. Responses were considered correct if the true diagnosis was included in the top three LLM suggestions. Llama-3-70B evaluated LLM responses, with its accuracy validated against radiologist ratings in a case subset. Models were further tested on 60 non-public brain MRI cases from a tertiary hospital to assess generalizability. Llama-3-70B demonstrated superior performance, followed by Gemma-2-27B and Mixtral-8x-7B. Similar performance results were found in the non-public dataset, where Llama-3-70B, Gemma-2-27B, and Mixtral-8x-7B again emerged as the top models. Our findings highlight the potential of open-source LLMs as decision support tools for radiological differential diagnosis in challenging, real-world cases.