bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruptions in Standard Care in Patients After Arthroscopic Rotator Cuff Repair During the COVID-19 Pandemic
Authors: Lee Donghoon , Destine Henson , Gibbs Brian S. , Lencer Adam J. , Paul Ryan W. , Palm Justin , Tjoumakaris Fotios P. 
Published: April 2023

Background: The coronavirus disease–2019 (COVID-19) pandemic led to disruptions in care for orthopaedic patients who underwent surgery just before the outbreak, rendering some unable to participate in standard postoperative care. Many of these patients underwent clinical follow-up and physical therapy via telehealth. Purpose: To evaluate the methods of postoperative care in patients who underwent arthroscopic rotator cuff repair (RCR) and had follow-ups during the height of the pandemic versus those who received prior standard of care. We aimed to compare the 1-year outcomes between these cohorts. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective chart review was used to identify patients who underwent primary RCR in February and March 2020 (COVID cohort) and the same period in 2019 (control cohort) at a single institution. Excluded were patients who underwent revision RCR, used workers’ compensation, or were incarcerated or deceased. The included patients reported the postoperative care received, their satisfaction with care, physical therapy appointment type (in person, home based, telehealth, or self-guided), satisfaction with physical therapy, and minimum 1-year postoperative American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and Penn Shoulder Score (PSS) outcomes. Results: Overall, 428 patients were included for final analysis—–199 in the COVID cohort and 229 controls. Follow-up data were collected for 160 patients in the COVID group (80.4%) and 169 control patients (73.8%). In the COVID group, 110 patients (68.8%) had ≥1 clinical visit conducted via telehealth, compared with zero in the control group. There were no differences between the COVID and control groups in the ASES (84.2 ± 16.5 vs 86.5 ± 17; P = .27 ), SANE (83.9 ± 15.4 vs 84.8 ± 17.5; P = .66), PSS (84.8 ± 15.3 vs 87.1 ± 15.1; P = .22), or patient satisfaction with the care received (81.7 ± 22.6 vs 86.3 ± 23.5; P = .09). Satisfaction with physical therapy was significantly higher in the control group (88.3 ± 18.9 vs 81.9 ± 22.5; P = .01). Conclusion: Despite disruptions in care, RCR patients had comparable 1-year outcomes during the pandemic versus before the pandemic. Telehealth clinical follow-up appointments did not adversely affect patient-reported outcome measures and may be appropriate for RCR patients beyond the pandemic.
Clinical and Magnetic Resonance Imaging Outcomes After Human Cord Blood–Derived Mesenchymal Stem Cell Implantation for Chondral Defects of the Knee
Authors: Song Jun-Seob , Hong Ki-Taek , Kim Na-Min , Hwangbo Byung-Hun , Yang Bong-Seok , Victoroff Brian N. , Choi Nam-Hong 
Published: April 2023

Background: There is a paucity of literature reporting clinical and magnetic resonance imaging (MRI) outcomes after allogeneic umbilical cord blood–derived mesenchymal stem cell (UCB-MSC) implantation for chondral defects of the knee. Purpose: To report clinical and MRI outcomes after UCB-MSC implantation for chondral lesions of the knee. Study Design: Case series; Level of evidence, 4. Methods: Inclusion criteria were patients aged between 40 and 70 years with focal chondral lesions of grade 3 or 4 on the medial femoral condyle, defect sizes >4 cm2, and intact ligaments. Exclusion criteria were patients who required realignment osteotomy or who had a meniscal deficiency, ligamentous instability, or a concomitant full-thickness chondral defect in the lateral or patellofemoral compartment. A mixture of human UCB-MSCs and sodium hyaluronate was implanted into the chondral defect through mini-arthrotomy. MRI at 1-year follow-up was performed to evaluate repaired cartilage hypertrophy. Repaired cartilage thickness was measured, and hypertrophy was classified as grade 1 (<125%), grade 2 (<150%), or grade 3 (<200%). Patient-reported outcomes (PROs; International Knee Documentation Committee, visual analog scale for pain, and Western Ontario and McMaster Universities Osteoarthritis Index) were evaluated preoperatively and at 1, 2, and 3 years postoperatively. Repaired cartilage hypertrophy was evaluated for a correlation with PRO scores. Results: Enrolled were 85 patients with a mean age of 56.8 ± 6.1 years and a mean chondral defect size of 6.7 ± 2.0 cm2. At follow-up, a significant improvement in all PRO scores was seen compared with preoperatively ( P < .001 for all). MRI at 1-year follow-up demonstrated that 28 patients had grade 1 repaired cartilage hypertrophy, 41 patients had grade 2, and 16 patients had grade 3. MRI performed in 11 patients at 2 years after surgery indicated no difference in repaired cartilage hypertrophy between the 1- and 2-year time points. The grade of repaired cartilage hypertrophy did not correlate with PRO scores. Conclusion: Clinical outcomes improved significantly at short-term follow-up after UCB-MSC implantation. Although all patients showed repaired cartilage hypertrophy, it did not correlate with clinical outcomes.
Hyperuricemia in a patient with Waldenström’s Macroglobulinemia: An innocent bystander?
Authors: Smith Zachary , Goyal Pankaj , Pandya Vrajesh , Thakar Charuhas V , Gudsoorkar Prakash S 
Published: April 2023

Background: Paraproteins often cause factitious biochemical measurements by forming opaque precipitates with the test reagents and interfering with various automated assays. These interferences may be difficult to anticipate as they are intermittent and patient-specific. Increased IgM has been shown to result in the underestimation of uric acid levels and pseudo-hypouricemia; however, there are no reported cases of pseudo-hyperuricemia in the setting of paraproteinemia. Case presentation: We present a case of Waldenström’s Macroglobulinemia (WM), resulting in a marked elevation of the uric acid level in the absence of tumor lysis syndrome (TLS). On evaluation, it was noted that the elevation in the uric acid levels was spurious, potentially due to high IgM levels resulting in increased serum viscosity. Identifying actual and pseudo-abnormal laboratory results is critical to guide further workup and conserve scarce healthcare resources. The absence of other concomitant laboratory abnormalities and clinical symptoms should raise a suspicion of factitious results. In addition to uric acid, many other assays are affected by paraproteinemia, commonly including electrolytes, lipids, glucose, and liver function tests.
Emerging roles and opportunities for rare disease patient advocacy groups
Authors: Patterson Amy M. , O’Boyle Megan , VanNoy Grace E. , Dies Kira A. 
Published: April 2023

Background: Patient advocacy groups (PAGs) serve a vital role for rare disease patients and families by providing educational resources, support, and a sense of community. Motivated by patient need, PAGs are increasingly at the forefront of policy, research, and drug development for their disease of interest. Objectives: The study explored the current landscape of PAGs in order to guide new and existing PAGs on available resources and challenges to research engagement. We aim to inform industry, advocates, and healthcare personnel about PAG achievements and ways they are increasingly involved in research. Design: We chose PAGs from the Rare Diseases Clinical Research Network (RDCRN) Coalition for Patient Advocacy Groups (CPAG) listserv and the National Organization for Rare Disorders (NORD) ‘Find a patient organization’. Methods: We surveyed eligible PAG leaders about the demographics, goals, and research activities of their organization. For analysis, PAGs were bucketed by size, age, prevalence of disease, and budget. Data were de-identified for cross-tabulation and multinomial logistic regression analysis with R. Results: Research engagement was an extremely important goal for most PAGs (81%), though ultra-rare disease and high-budget PAGs were most likely to cite it as the top priority. In total, 79% reported research engagement in some capacity, including registries, translational research, and clinical trials. ‘Ultra-rare’ PAGs were less likely than ‘rare’ PAGs to have an ongoing clinical trial. Conclusion: While PAGs of varying sizes, budgets, and maturity levels reported an interest in research, limited funding and lack of disease awareness continue to create barriers to achieving their goals. While support tools exist to make research more accessible, often their utility depends on the funding, sustainability, maturity of the PAG itself, and the level of investment of collaborators. Despite the availability of current support systems, there are challenges related to both the start-up and sustainability of patient-centric research efforts.
4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling
Authors: Xu Lujun , Cai Juan , Li Chenrui , Yang Ming , Duan Tongyue , Zhao Qing , Xi Yiyun , Sun Liya , He Liyu , Tang Chengyuan , Sun Lin 
Published: April 2023

Abstract
Background
Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process. 4-octyl itaconate (4-OI) is a multi-target itaconate derivative with potent anti-inflammatory action. However, it remains elusive whether and how 4-OI contributes to the regulation of S-AKI.

Methods
We employed a lipopolysaccharide (LPS)-induced AKI murine model and explored the potential renoprotective effect of 4-OI in vivo. In vitro experiments, BUMPT cells, a murine renal tubular cell line, were conducted to examine the effects of 4-OI on inflammation, oxidative stress, and mitophagy. Moreover, STAT3 plasmid was transfected in BUMPT cells to investigate the role of STAT3 signaling in the 4-OI-administrated state.

Results
We demonstrate that 4-OI protects against S-AKI through suppressing inflammation and oxidative stress and enhancing mitophagy. 4-OI significantly reduced the levels of Scr, BUN, Ngal as well as the tubular injury in LPS-induced AKI mice. 4-OI restrained inflammation by reducing macrophage infiltration and suppressing the expression of IL-1β and NLRP3 in the septic kidney. 4-OI also reduced ROS levels, as well as cleaved caspase-3 and boosted antioxidants such as HO-1, and NQO1 in mice. In addition, the 4-OI treatment significantly promoted mitophagy. Mechanistically, 4-OI activated Nrf2 signaling and suppressed phosphorylated STAT3 in vivo and vitro. Molecular docking revealed the binding affinity of 4-OI towards STAT3. ML385, a specific Nrf2 inhibitor, partially repressed the anti-inflammatory and anti-oxidative effects of 4-OI and partially restricted the mitophagy induced by 4-OI in vivo and in vitro. Transfected with STAT3 plasmid partially suppressed mitophagy and the anti-inflammatory effect provoked by 4-OI in vitro.

Conclusion
These data suggest that 4-OI ameliorates LPS-induced AKI by suppressing inflammation and oxidative stress and enhancing mitophagy through the overactivation of the Nrf2 signaling pathway, and inactivation of STAT3. Our study identifies 4-OI as a promising pharmacologic for S-AKI.
ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response
Authors: Liu Yifei , Zhang Lei , Zhang Shumin , Liu Jialu , Li Xiaohui , Yang Kexin , Yang Danyi , Liu Yu , Sun Lin , Liu Fuyou , Xiao Li 
Published: April 2023

Abstract
Background
Mitochondrial quality control (MQC) plays a critical role in the progression of tubulointerstitial injury in diabetic kidney disease (DKD). The mitochondrial unfolded protein response (UPRmt), which is an important MQC process, is activated to maintain mitochondrial protein homeostasis in response to mitochondrial stress. Activating transcription factor 5 (ATF5) is critical in the mammalian UPRmt via mitochondria-nuclear translocation. However, the role of ATF5 and UPRmt in tubular injury under DKD conditions is unknown.

Methods
ATF5 and UPRmt-related proteins including heat shock protein 60 (HSP60) and Lon peptidase 1 (LONP1), in DKD patients and db/db mice were examined by immunohistochemistry (IHC) and western blot analysis. Eight-week-old db/db mice were injected with ATF5-shRNA lentiviruses via the tail vein, and a negative lentivirus was used as a control. The mice were euthanized at 12 weeks, and dihydroethidium (DHE) and TdT-mediated dUTP nick end labeling (TUNEL) assays were performed to evaluate reactive oxygen species (ROS) production and apoptosis in kidney sections, respectively. In vitro, ATF5-siRNA, ATF5 overexpression plasmids or HSP60-siRNA were transfected into HK-2 cells to evaluate the effect of ATF5 and HSP60 on tubular injury under ambient hyperglycemic conditions. Mitochondrial superoxide (MitoSOX) staining was used to gauge mitochondrial oxidative stress levels, and the early stage of cell apoptosis was examined by Annexin V-FITC kits.

Results
Increased ATF5, HSP60 and LONP1 expression was observed in the kidney tissue of DKD patients and db/db mice and was tightly correlated with tubular damage. The inhibition of HSP60 and LONP1, improvements in serum creatinine, tubulointerstitial fibrosis and apoptosis were observed in db/db mice treated with lentiviruses carrying ATF5 shRNA. In vitro, the expression of ATF5 was increased in HK-2 cells exposed to high glucose (HG) in a time-dependent manner, which was accompanied by the overexpression of HSP60, fibronectin (FN) and cleaved-caspase3 (C-CAS3). ATF5-siRNA transfection inhibited the expression of HSP60 and LONP1, which was accompanied by reduced oxidative stress and apoptosis in HK-2 cells exposed to sustained exogenous high glucose. ATF5 overexpression exacerbated these impairments. HSP60-siRNA transfection blocked the effect of ATF5 on HK-2 cells exposed to continuous HG treatment. Interestingly, ATF5 inhibition exacerbated mitochondrial ROS levels and apoptosis in HK-2 cells in the early period of HG intervention (6 h).

Conclusions
ATF5 could exert a protective effect in a very early stage but promoted tubulointerstitial injury by regulating HSP60 and the UPRmt pathway under DKD conditions, providing a potential target for the prevention of DKD progression.
Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data
Authors: Bornhofen Elesandro , Fè Dario , Nagy Istvan , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian S. , Asp Torben , Janss Luc 
Published: April 2023

Abstract
Background
Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce.

Results
Our results identified substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizing L. perenne with another species within the genus (L. multiflorum) relative to across genera (F. pratensis). However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled and all available regressors.

Conclusions
The utilization of computational techniques for the reconstruction of co-expression networks facilitates the identification of key omic features that serve as central nodes and demonstrate correlation with the manifestation of observed traits. Our results also indicate a robust association between early multi-omic traits measured in a greenhouse setting and phenotypic traits evaluated under field conditions.
Antibacterial, antibiofilm, and anti-quorum sensing activities of pyocyanin against methicillin-resistant Staphylococcus aureus: in vitro and in vivo study
Authors: Kamer Amal M. Abo , Abdelaziz Ahmed A. , Al-Monofy Khaled B. , Al-Madboly Lamiaa A. 
Published: April 2023

Abstract
Background
Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered a major public health problem, as the treatment options are restricted. Biofilm formation and the quorum sensing (QS) system play a pivotal role in S. aureus pathogenicity. Hence, this study was performed to explore the antibacterial effect of pyocyanin (PCN) on MRSA as well as its effect on MRSA biofilm and QS.

Results
Data revealed that PCN exhibited strong antibacterial activity against all test MRSA isolates (n = 30) with a MIC value equal to 8 µg/ml. About 88% of MRSA biofilms were eradicated by PCN treatment using the crystal violet assay. The disruption of MRSA biofilm was confirmed using confocal laser scanning microscopy, which showed a reduction in bacterial viability (approximately equal to 82%) and biofilm thickness (approximately equal to 60%). Additionally, the disruption of the formation of microcolonies and the disturbance of the connection between bacterial cells in the MRSA biofilm after PCN treatment were examined by scanning electron microscopy. The 1/2 and 1/4 MICs of PCN exerted promising anti-QS activity without affecting bacterial viability; Agr QS-dependent virulence factors (hemolysin, protease, and motility), and the expression of agrA gene, decreased after PCN treatment. The in silico analysis confirmed the binding of PCN to the AgrA protein active site, which blocked its action. The in vivo study using the rat wound infection model confirmed the ability of PCN to modulate the biofilm and QS of MRSA isolates.

Conclusion
The extracted PCN seems to be a good candidate for treating MRSA infection through biofilm eradication and Agr QS inhibition.
The pan-plastome of tartary buckwheat (fagopyrum tataricum): key insights into genetic diversity and the history of lineage divergence
Authors: Zhou Jiawei , He Wenchuang , Wang Jie , Liao Xuezhu , Xiang Kunli , Ma Mingchuan , Liu Zhang , Li Yongyao , Tembrock Luke R. , Wu Zhiqiang , Liu Longlong 
Published: April 2023

Abstract
Background
Tartary buckwheat (Fagopyrum tataricum) is an important food and medicine crop plant, which has been cultivated for 4000 years. A nuclear genome has been generated for this species, while an intraspecific pan-plastome has yet to be produced. As such a detailed understanding of the maternal genealogy of Tartary buckwheat has not been thoroughly investigated.

Results
In this study, we de novo assembled 513 complete plastomes of Fagopyrum and compared with 8 complete plastomes of Fagopyrum downloaded from the NCBI database to construct a pan-plastome for F. tartaricum and resolve genomic variation. The complete plastomes of the 513 newly assembled Fagopyrum plastome sizes ranged from 159,253 bp to 159,576 bp with total GC contents ranged from 37.76 to 37.97%. These plastomes all maintained the typical quadripartite structure, consisting of a pair of inverted repeat regions (IRA and IRB) separated by a large single copy region (LSC) and a small single copy region (SSC). Although the structure and gene content of the Fagopyrum plastomes are conserved, numerous nucleotide variations were detected from which population structure could be resolved. The nucleotide variants were most abundant in the non-coding regions of the genome and of those the intergenic regions had the most. Mutational hotspots were primarily found in the LSC regions. The complete 521 Fagopyrum plastomes were divided into five genetic clusters, among which 509 Tartary buckwheat plastomes were divided into three genetic clusters (Ft-I/Ft-II/Ft-III). The genetic diversity in the Tartary buckwheat genetic clusters was the greatest in Ft-III, and the genetic distance between Ft-I and Ft-II was the largest. Based on the results of population structure and genetic diversity analysis, Ft-III was further subdivided into three subgroups Ft-IIIa, Ft-IIIb, and Ft-IIIc. Divergence time estimation indicated that the genera Fagopyrum and Rheum (rhubarb) shared a common ancestor about 48 million years ago (mya) and that intraspecies divergence in Tartary buckwheat began around 0.42 mya.

Conclusions
The resolution of pan-plastome diversity in Tartary buckwheat provides an important resource for future projects such as marker-assisted breeding and germplasm preservation.
“Because it eases my Childbirth Plan”: a qualitative study on factors contributing to preferences for caesarean section in Thailand
Authors: Nuampa Sasitara , Ratinthorn Ameporn , Lumbiganon Pisake , Rungreangkulkij Somporn , Rujiraprasert Nilubon , Buaboon Natthapat , Jampathong Nampet , Dumont Alexandre , Hanson Claudia , de Loenzien Myriam , Bohren Meghan A. , Betrán Ana Pilar 
Published: April 2023

Abstract
Background
Although caesarean section (CS) rates have increased rapidly in Thailand, the upward trend is not supported by significant maternal or perinatal health benefits. The appropriate use of CS through QUALIty DECision-making by women and providers (QUALI-DEC project) aims to design and implement a strategy to optimize the use of CS through non-clinical interventions. This study aimed to explore the factors influencing women’s and health professionals’ preferences for CS delivery in Thailand.

Methods
We conducted a formative qualitative study by using semi-structured in-depth interviews with pregnant and postpartum women, and healthcare staff. Purposive sampling was used to recruit participants from eight hospitals across four regions of Thailand. Content analysis was used to develop the main themes.

Results
There were 78 participants, including 27 pregnant and 25 postpartum women, 8 administrators, 13 obstetricians, and 5 interns. We identified three main themes and seven sub-themes of women and healthcare providers’ perceptions on CS: (1) avoiding the negative experiences from vaginal birth (the pain of labor and childbirth, uncertainty during the labor period); (2) CS is a safer mode of birth (guarantees the baby’s safety, a protective shield for doctors); and (3) CS facilitates time management (baby’s destiny at an auspicious time, family’s management, manage my work/time).

Conclusions
Women mentioned negative experiences and beliefs about vaginal delivery, labor pain, and uncertain delivery outcomes as important factors influencing CS preferences. On the other hand, CS is safer for babies and facilitates multiple tasks in women’s lives. From health professionals’ perspectives, CS is the easier and safer method for patients and them. Interventions to reduce unnecessary CS, including QUALI-DEC, should be designed and implemented, taking into consideration the perceptions of both women and healthcare providers.