bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a New Integrative Health and Wellness Clinic for Veterans at the San Francisco VA Health Care System: A Mixed-Methods Pilot Study
Authors: Nicosia Francesca M , Purcell Natalie , Bertenthal Dan , Usman Hajra , Seidel Ilana , McGrath Sarah , Hildebrand Caitlin , McCarthy Brittan , Seal Karen H 
Published: June 2024

Objective The Integrative Health and Wellness Clinic (IHWC), established in 2019 at the San Francisco VA Health Care System, is an interdisciplinary clinic consisting of a medical provider, dietician, physical therapist, and psychologist trained in complementary and integrative health (CIH) following the VA Whole Health model of care. Veterans with complex chronic conditions seeking CIH and nonpharmacologic approaches are referred to the IHWC. This study evaluated the clinic’s acceptability and feasibility among veteran patients and its preliminary impact on health and wellbeing, health-related goals, and use of CIH approaches. Methods Mixed methods were used to assess patient-reported outcomes and experiences with the IHWC. Participants completed surveys administered at baseline and 6-months and a subset completed a qualitative interview. Pre- and post-scores were compared using t-tests and chi-square tests. Results Thirty-five veterans completed baseline and 6-month follow up surveys. Of these, 13% were women; 24% < 50 years of age, and 44% identified as racial/ethnic minorities. Compared to baseline, at 6 months, there were significant ( P < .05) improvements in overall health, physical health, perceived stress, and perceived helpfulness of clinicians in assisting with goal attainment; there was a trend toward improved mental health ( P = .057). Interviews (n = 25) indicated satisfaction with the interdisciplinary clinical model, support of IHWC providers in goal attainment, and positive impact on physical and mental health. Areas for improvement included logistics related to scheduling of multiple IHWC providers and referrals to other CIH services. Conclusion Results revealed significant improvement in important clinical domains and satisfaction with interprofessional IHWC clinic providers, but also opportunities to improve clinic processes and care coordination. An interdisciplinary clinic focused on CIH and Whole Health is a feasible and acceptable model of care for veterans with complex chronic health conditions in the VA healthcare system.
Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants
Authors: Gui Meilin , He Miao , Qin Lixia 
Published: June 2024

Abstract
Background
Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon.

Case presentation
In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient's symptoms deteriorated rapidly following a COVID-19 infection.

Conclusions
In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it's extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.
Safety and efficacy of multi-target TKI combined with nivolumab in check-point inhibitor-refractory patients with advanced NSCLC: a prospective, single-arm, two-stage study
Authors: Zhang Bo , Liu Hongyu , Shi Chunlei , Gao Zhiqiang , Zhong Runbo , Gu Aiqin , Chu Tianqing , Wang Huimin , Xiong Liwen , Zhang Wei , Zhang Xueyan , Yan Bo , Teng Jiajun , Wang Weimin , Bai Hao , Qiao Rong , Cheng Lei , Kuang Yanbin , Zhao Ruiying , Zhong Hua , Han Baohui 
Published: June 2024

Abstract
Background
Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs.

Methods
This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively.

Results
Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively.

Conclusion
Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted.

Trial registration
NCT04507906 August 11, 2020.
Diagnostic performance of Node Reporting and Data System (Node-RADS) for assessing mesorectal lymph node in rectal cancer by CT
Authors: Niu Yue , Wen Lu , Yang Yanhui , Zhang Yi , Fu Yi , Lu Qiang , Wang Yu , Yu Xiao , Yu Xiaoping 
Published: June 2024

Abstract
Background
To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment.

Methods
Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated.

Results
Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05).

Conclusions
The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.
Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis
Authors: El Zein Lulwa , Smith Wendy M. , White Launia J. , Hodge David O. , Olsen Timothy W. , Pulido Jose S. , Dalvin Lauren A. 
Published: June 2024

Abstract
Background
Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides.

Methods
Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022.
The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included.

Results
There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis.

Conclusion
OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.
Collaboration in the return-to-work process after sick leave due to common mental disorders: a qualitative study of stakeholders’ views on goals and roles
Authors: Svärd Veronica , Arapovic Johansson Zana , Holmlund Lisa , Hellman Therese , Kwak Lydia , Björk Brämberg Elisabeth 
Published: June 2024

Abstract
Background
This study explores how the goals of collaboration in the return-to-work (RTW) process for people with common mental disorders are described by the stakeholders involved, and how they experience stakeholders’ roles and responsibilities in relation to these goals.

Methods
Interviews were conducted with 41 participants from three Swedish regions. Nine of the participants were workers, six employer representatives, four occupational health professionals, four social insurance officers, 18 RTW coordinators and five physicians. Thematic analysis was conducted.

Results
Three main themes and overarching goals when collaborating on RTW were identified. In the first theme, ‘creating an informative environment’, all stakeholders emphasised clear roles and responsibilities. The second theme, ‘striving for consensus in an environment of negotiations’, addressed negotiations about when and how to collaborate, on what and with whom, and reveal different views on stakeholders’ goals, roles and responsibilities in collaboration. The third theme identified goals for ‘creating a supportive environment’ for both workers and other stakeholders. Coordinators are found to have an important role in achieving a supportive environment, and in neutralising power imbalances between workers and their employers and social insurance officers.

Conclusions
Competing goals and priorities were identified as hindering successful collaboration, contributing to a spectrum of complex versus easy RTW collaboration. This study suggests some basic conditions for achieving a collaborative arena that is neutral in terms of power balance, where all stakeholders can share their views.
Examination of learning ability development through the implementation of the “autonomy-collaboration” learning mode grounded in evidence-based medicine practice
Authors: Li Xiao-Huan , Zhang Qing , Li Chun , Yin Ya-Lei , Yang Zhen , Fu Ying , Yuan Xiao-Lin 
Published: June 2024

Abstract
Objective
Currently, there are still some shortcomings in EBM education in China.The study aimed to investigate the effectiveness of the novel evidence-based medicine (EBM) learning model of “autonomy-collaboration.”

Methods
A total of 91 undergraduate students majoring in clinical medicine at Zhongshan Clinical College of Dalian University from the 2019 batch were selected as the participants in this study. They were instructed to follow the EBM learning model of “autonomy-collaboration.” Upon completion of the course, questionnaires, records of participants’ sentiments and insights, and evidence-based clinical practice reports were used as indicators to evaluate the effectiveness of the training.

Results
This learning modality effectively enhanced independent learning ability of the students, stimulated their interest in learning, and strengthened the communication between students and teachers, thereby improving the quality of teaching.

Conclusion
The novel EBM learning model of “autonomy-collaboration,” exhibited robust effectiveness in instruction and facilitated the seamless integration of theoretical knowledge with clinical practice. Consequently, its widespread adoption is strongly recommended.
Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation
Authors: Babendreyer Aaron , Kieselhorst Julia , Rinkens Cindy , Lyashenko Anastasia M. , Düsterhöft Stefan , Jahr Holger , Craveiro Rogerio B. , Wolf Michael , Ludwig Andreas 
Published: June 2024

AbstractBone resorption is driven through osteoclast differentiation by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-Β ligand (RANKL). We noted that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 are downregulated at the expression level during osteoclast differentiation of the murine monocytic cell line RAW264.7 in response to RANKL. Both proteinases are well known to shed a variety of single-pass transmembrane molecules from the cell surface. We further showed that inhibitors of ADAM10 or ADAM17 promote osteoclastic differentiation and furthermore enhance the surface expression of receptors for RANKL and M-CSF on RAW264.7 cells. Using murine bone marrow-derived monocytic cells (BMDMCs), we demonstrated that a genetic deficiency of ADAM17 or its required regulator iRhom2 leads to increased osteoclast development in response to M-CSF and RANKL stimulation. Moreover, ADAM17-deficient osteoclast precursor cells express increased levels of the receptors for RANKL and M-CSF. Thus, ADAM17 negatively regulates osteoclast differentiation, most likely through shedding of these receptors. To assess the time-dependent contribution of ADAM10, we blocked this proteinase by adding a specific inhibitor on day 0 of BMDMC stimulation with M-CSF or on day 7 of subsequent stimulation with RANKL. Only ADAM10 inhibition beginning on day 7 increased the size of developing osteoclasts indicating that ADAM10 suppresses osteoclast differentiation at a later stage. Finally, we could confirm our findings in human peripheral blood mononuclear cells (PBMCs). Thus, downregulation of either ADAM10 or ADAM17 during osteoclast differentiation may represent a novel regulatory mechanism to enhance their differentiation process. Enhanced bone resorption is a critical issue in osteoporosis and is driven through osteoclast differentiation by specific osteogenic mediators. The present study demonstrated that the metalloproteinases ADAM17 and ADAM10 critically suppress osteoclast development. This was observed for a murine cell line, for isolated murine bone marrow cells and for human blood cells by either preferential inhibition of the proteinases or by gene knockout. As a possible mechanism, we studied the surface expression of critical receptors for osteogenic mediators on developing osteoclasts. Our findings revealed that the suppressive effects of ADAM17 and ADAM10 on osteoclastogenesis can be explained in part by the proteolytic cleavage of surface receptors by ADAM10 and ADAM17, which reduces the sensitivity of these cells to osteogenic mediators. We also observed that osteoclast differentiation was associated with the downregulation of ADAM10 and ADAM17, which reduced their suppressive effects. We therefore propose that this downregulation serves as a feedback loop for enhancing osteoclast development.
Reliability and reproducibility of the venous excess ultrasound (VExUS) score, a multi-site prospective study: validating a novel ultrasound technique for comprehensive assessment of venous congestion
Authors: Longino August A. , Martin Katharine C. , Leyba Katarina R. , McCormack Luke , Siegel Gabriel , Sharma Vibhu M. , Riscinti Matthew , Lopez Carolina O. , Douglas Ivor S. , Gill Edward A. 
Published: June 2024

AbstractThough the novel venous excess ultrasound (VExUS) score is increasingly used as a noninvasive means of venous congestion measurement, the inter-rater reliability (IRR), inter-user reproducibility (IUR), and utility of concurrent ECG have not been evaluated. We conducted a multicenter study of the IRR, IUR, and utility of ECG for VExUS interpretation between four attending physicians of diverse specialties, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR for scans with and without ECG. Eighty-four paired VExUS exams from 42 patients, 60 of which had a concurrent ECG tracing, were interpreted. They showed substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8. There was greater agreement among images with an ECG tracing. These results suggest that ECG-augmented VExUS may be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.
Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC)
Authors: Kunz Julius Valentin , Hansmann Helena , Fähndrich Mareike , Pigorsch Mareen , Bethke Nicole , Peters Harm , Krüger Anne , Schroeder Tim , Marcy Florian , Magomedov Abakar , Müller-Redetzky Holger , Eckardt Kai-Uwe , Khadzhynov Dmytro , Enghard Philipp 
Published: June 2024

Abstract
Background
Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT.

Methods
We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité—Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment.

Results
From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26).

Conclusion
Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS.

Trial registration
The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.
Nutraceuticals as components of sustainable poultry production systems for food and nutrition security in Africa: a review
Authors: Mnisi Caven Mguvane , Mlambo Victor , Montso Peter Kotsoana , Manyeula Freddy , Kumanda Cebisa , Moreki John Cassius 
Published: June 2024

AbstractPoultry production plays a key role in reducing food and nutrition insecurity in developing countries. However, as the poultry industry continues to grow, its future is in doubt due to economic, environmental, and social sustainability challenges. To address these challenges, poultry production practices must be optimized for food security, human health, economic viability, and environmental stewardship. At the core of this sustainability endeavour are the substantial nutritional and health requirements of birds that are raised intensively. Nutrient-dense feed resources such as maize and soybeans are indispensable in most poultry production systems in Africa, yet these grains are also direct nutrient sources for humans. This has increased their demand and prices on the world market. In addition, frequent disease outbreaks pose viability challenges that are traditionally mitigated using antibiotic growth promoters (AGPs). However, this practice has led to the undesirable propagation of antibiotic-resistant microbes and production of antibiotic residue-containing poultry products. Alternatives to AGPs such as phytogenic products are required to address some of these challenges. Phytogenics contain nutraceuticals that can boost feed efficiency, bird immunity, and product quality without the negative outcomes associated with AGPs, thus promoting sustainable poultry production. However, phytogenics have not been widely adopted in the poultry industry for a variety of reasons, which are interrogated in this review. The objective of this paper is to explore and evaluate the role of nutraceuticals in sustainable poultry production systems and how they can be used to enhance food and nutrition security in Africa. Optimal usage of phytogenics has the potential to sustain poultry meat and egg production as primary animal protein sources for a growing global human population, especially in developing countries.