bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Current Clinical Practice Guidelines on Intra-articular Hyaluronic Acid, Corticosteroid, and Platelet-Rich Plasma Injection for Knee Osteoarthritis: An International Perspective
Authors: Phillips Mark , Bhandari Mohit , Grant John , Bedi Asheesh , Trojian Thomas , Johnson Aaron , Schemitsch Emil 
Published: August 2021

Background: There are many clinical practice guidelines (CPGs) for the prevention, diagnosis, and treatment of knee osteoarthritis (OA). They differ by region, considering local health care systems, along with cultural and economic factors. Currently, there are conflicting CPG recommendations across the various publications, which makes it difficult for clinicians to fully understand the optimal treatment decisions for knee OA management. Purpose: To summarize the current published CPG recommendations for the role of injections in the nonoperative management of knee OA, specifically with the use of intra-articular hyaluronic acid (IA-HA), intra-articular corticosteroids (IA-CS), and platelet-rich plasma (PRP). Study Design: Systematic review. Methods: A comprehensive search identified all nonoperative knee OA CPGs within the ECRI (formerly Emergency Care Research Institute) Guidelines Trust database, the Guidelines International Network database, Google Scholar, and the Trip (formerly Turning Research Into Practice) database. Guideline recommendations were categorized into strong, conditional, or uncertain recommendations for or against the use of IA-HA, IA-CS, or PRP. Guideline recommendations were summarized and depicted graphically to identify trends in recommendations over time. Results: The search strategy identified 27 CPGs that provided recommendations. There were 20 recommendations in favor of IA-HA use, 21 recommendations in favor of IA-CS use, and 9 recommendations that were uncertain or unable to make a formal recommendation for or against PRP use based on current evidence. Most recommendations considered IA-HA and IA-CS use for symptom relief when other nonoperative options are ineffective. IA-CS were noted to provide fast and short-acting symptom relief for acute episodes of disease exacerbation, while IA-HA may demonstrate a relatively delayed but prolonged effect in comparison. The CPGs concluded that PRP recommendations currently lack evidence to definitively recommend for or against use. Conclusion: Available CPGs provide recommendations on injectables for knee OA treatment. General guidance from a global perspective concluded that IA-CS and IA-HA are favored for different needed responses and can be utilized within the knee OA treatment paradigm, while PRP currently has insufficient evidence to make a conclusive recommendation for or against its use.
Association Between Racial Disparities in Hospital Length of Stay and the Hospital Readmission Reduction Program
Authors: Ghosh Arnab K. , Soroka Orysya , Shapiro Martin , Unruh Mark A. 
Published: August 2021

Background: On average Black patients have longer LOS than comparable White patients. Longer hospital length of stay (LOS) may be associated with higher readmission risk. However, evidence suggests that the Hospital Readmission Reduction Program (HRRP) reduced overall racial differences in 30-day adjusted readmission risk. Yet, it is unclear whether the HRRP narrowed these LOS racial differences. Objective: We examined the relationship between Medicare-insured Black-White differences in average, adjusted LOS (ALOS) and the HRRP’s implementation and evaluation periods. Methods: Using 2009-2017 data from State Inpatient Dataset from New York, New Jersey, and Florida, we employed an interrupted time series analysis with multivariate generalized regression models controlling for patient, disease, and hospital characteristics. Results are reported per 100 admissions. Results: We found that for those discharged home, Black-White ALOS differences significantly widened by 4.15 days per 100 admissions (95% CI: 1.19 to 7.11, P < 0.001) for targeted conditions from before to after the HRRP implementation period, but narrowed in the HRRP evaluation period by 1.84 days per 100 admissions for every year-quarter (95% CI: −2.86 to −0.82, P < 0.001); for those discharged to non-home destinations, there was no significant change between HRRP periods, but ALOS differences widened over the study period. Black-White ALOS differences for non-targeted conditions remained unchanged regardless of HRRP phase and discharge destination. Conclusion: Increased LOS for Black patients may have played a role in reducing Black-White disparities in 30-day readmission risks for targeted conditions among patients discharged to home.
IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB– and caspase-8–dependent mechanisms
Authors: Zhou Liang , Zhang Yu , Meads Mark B. , Dai Yun , Ning Yanxia , Hu Xiaoyan , Li Lin , Sharma Kanika , Nkwocha Jewel , Parker Rebecca , Bui Danny , McCarter Jacquelyn , Kramer Lora , Purcell Cullen , Sudalagunta Praneeth R. , Canevarolo Rafael R. , Coelho Siqueira Silva Maria D. , De Avila Gabriel , Alugubelli Raghunandan Reddy , Silva Ariosto S. , Kmeiciak Maciej , Ferreira-Gonzalez Andrea , Shain Kenneth H. , Grant Steven 
Published: August 2021

Abstract
Interactions between the inhibitor of apoptosis protein antagonist LCL161 and the histone deacetylase inhibitor panobinostat (LBH589) were examined in human multiple myeloma (MM) cells. LCL161 and panobinostat interacted synergistically to induce apoptosis in diverse MM cell lines, including those resistant to bortezomib (PS-R). Similar interactions were observed with other histone deacetylase inhibitors (MS-275) or inhibitors of apoptosis protein antagonists (birinapant). These events were associated with downregulation of the noncanonical (but not the canonical) NF-κB pathway and activation of the extrinsic, caspase-8–related apoptotic cascade. Coexposure of MM cells to LCL161/LBH589 induced TRAF3 upregulation and led to TRAF2 and NIK downregulation, diminished expression of BCL-XL, and induction of γH2A.X. Ectopic expression of TRAF2, NIK, or BCL-XL, or short hairpin RNA TRAF3 knock-down, significantly reduced LCL161/LBH589 lethality, as did ectopic expression of dominant-negative FADD. Stromal/microenvironmental factors failed to diminish LCL161/LBH589–induced cell death. The LCL161/LBH589 regimen significantly increased cell killing in primary CD138+ cells (N = 31) and was particularly effective in diminishing the primitive progenitor cell–enriched CD138–/19+/20+/27+ population (N = 23) but was nontoxic to normal CD34+ cells. Finally, combined LCL161/LBH589 treatment significantly increased survival compared with single-agent treatment in an immunocompetent 5TGM1 murine MM model. Together, these findings argue that LCL161 interacts synergistically with LBH589 in MM cells through a process involving inactivation of the noncanonical NF-κB pathway and activation of the extrinsic apoptotic pathway, upregulation of TRAF3, and downregulation of TRAF2/BCL-XL. Notably, this regimen overcomes various forms of resistance, is active against primary MM cells, and displays significant in vivo activity. This strategy warrants further consideration in MM.
Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation
Authors: Xu Jane Jialu , Chalk Alistair M. , Nikolic Iva , Simpson Kaylene J. , Smeets Monique F. , Walkley Carl R. 
Published: August 2021

Abstract
Current strategies to target RNA splicing mutant myeloid cancers proposes targeting the remaining splicing apparatus. This approach has only been modestly sensitizing and is also toxic to non-mutant-bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of missplicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (acute myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia) was performed to identify conserved missplicing events. From this analysis, we identified that the cell-cycle and DNA repair pathways were overrepresented within the conserved misspliced transcript sets. In parallel, to functionally define pathways essential for survival and proliferation of Srsf2P95H/+ cells, we performed a genome-wide Clustered regularly interspaced short palindromic repeat loss-of-function screen using Hoxb8 immortalized R26-CreERki/+Srsf2P95H/+ and R26-CreERki/+Srsf2+/+ cell lines. We assessed loss of single guide RNA representation at 3 timepoints: immediately after Srsf2P95H/+ activation, and at 1 week and 2 weeks after Srsf2P95H/+ mutation. Pathway analysis demonstrated that the cell-cycle and DNA damage response pathways were among the top synthetic lethal pathways with Srsf2P95H/+ mutation. Based on the loss of guide RNAs targeting Cdk6, we identified that palbociclib, a CDK6 inhibitor, showed preferential sensitivity in Srsf2P95H/+ cell lines and in primary nonimmortalized lin−cKIT+Sca-1+ cells compared with wild-type controls. Our data strongly suggest that the cell-cycle and DNA damage response pathways are required for Srsf2P95H/+ cell survival, and that palbociclib could be an alternative therapeutic option for targeting SRSF2 mutant cancers.
A new murineRpl5(uL18) mutation provides a unique model of variably penetrant Diamond-Blackfan anemia
Authors: Yu Lei , Lemay Philippe , Ludlow Alexander , Guyot Marie-Claude , Jones Morgan , Mohamed Fatma F. , Saroya Ghazi-Abdullah , Panaretos Christopher , Schneider Emily , Wang Yu , Myers Greggory , Khoriaty Rami , Li Qing , Franceschi Renny , Engel James Douglas , Kaartinen Vesa , Rothstein Thomas L. , Justice Monica J. , Kibar Zoha , Singh Sharon A. 
Published: August 2021

AbstractRibosome dysfunction is implicated in multiple abnormal developmental and disease states in humans. Heterozygous germline mutations in genes encoding ribosomal proteins are found in most individuals with Diamond-Blackfan anemia (DBA), whereas somatic mutations have been implicated in a variety of cancers and other disorders. Ribosomal protein-deficient animal models show variable phenotypes and penetrance, similar to human patients with DBA. In this study, we characterized a novel ENU mouse mutant (Skax23m1Jus) with growth and skeletal defects, cardiac malformations, and increased mortality. After genetic mapping and whole-exome sequencing, we identified an intronic Rpl5 mutation, which segregated with all affected mice. This mutation was associated with decreased ribosome generation, consistent with Rpl5 haploinsufficiency. Rpl5Skax23-Jus/+ animals had a profound delay in erythroid maturation and increased mortality at embryonic day (E) 12.5, which improved by E14.5. Surviving mutant animals had macrocytic anemia at birth, as well as evidence of ventricular septal defect (VSD). Surviving adult and aged mice exhibited no hematopoietic defect or VSD. We propose that this novel Rpl5Skax23-Jus/+ mutant mouse will be useful in studying the factors influencing the variable penetrance that is observed in DBA.
Distribution and diversity of dimetal-carboxylate halogenases in cyanobacteria
Authors: Eusebio Nadia , Rego Adriana , Glasser Nathaniel R. , Castelo-Branco Raquel , Balskus Emily P. , Leão Pedro N. 
Published: August 2021

Abstract
Background
Halogenation is a recurring feature in natural products, especially those from marine organisms. The selectivity with which halogenating enzymes act on their substrates renders halogenases interesting targets for biocatalyst development. Recently, CylC – the first predicted dimetal-carboxylate halogenase to be characterized – was shown to regio- and stereoselectively install a chlorine atom onto an unactivated carbon center during cylindrocyclophane biosynthesis. Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. Due to its novelty in biological catalysis, selectivity and ability to perform C-H activation, this halogenase class is of considerable fundamental and applied interest. The study of CylC-like enzymes will provide insights into substrate scope, mechanism and catalytic partners, and will also enable engineering these biocatalysts for similar or additional C-H activating functions. Still, little is known regarding the diversity and distribution of these enzymes.

Results
In this study, we used both genome mining and PCR-based screening to explore the genetic diversity of CylC homologs and their distribution in bacteria. While we found non-cyanobacterial homologs of these enzymes to be rare, we identified a large number of genes encoding CylC-like enzymes in publicly available cyanobacterial genomes and in our in-house culture collection of cyanobacteria. Genes encoding CylC homologs are widely distributed throughout the cyanobacterial tree of life, within biosynthetic gene clusters of distinct architectures (combination of unique gene groups). These enzymes are found in a variety of biosynthetic contexts, which include fatty-acid activating enzymes, type I or type III polyketide synthases, dialkylresorcinol-generating enzymes, monooxygenases or Rieske proteins. Our study also reveals that dimetal-carboxylate halogenases are among the most abundant types of halogenating enzymes in the phylum Cyanobacteria.

Conclusions
Our data show that dimetal-carboxylate halogenases are widely distributed throughout the Cyanobacteria phylum and that BGCs encoding CylC homologs are diverse and mostly uncharacterized. This work will help guide the search for new halogenating biocatalysts and natural product scaffolds.
Prediction of postoperative nausea and vomiting by point-of-care gastric ultrasound: can we improve complications and length of stay in emergency surgery? A cohort study
Authors: Cozza Valerio , Barberis Lorenzo , Altieri Gaia , Donatelli Mario , Sganga Gabriele , La Greca Antonio 
Published: August 2021

Abstract
Background
Postoperative nausea and vomiting and postoperative ileus are common after major digestive surgery and represent one of the significant problems in Acute Care Surgery.
The delivery model of emergency surgery needs to be improved in order to foster a patient-centered care.
The multimodal approach suggested by Enhanced Recovery After Surgery (ERAS®) Guidelines is gaining widespread acceptance but is difficult to apply to emergency surgery.
Ultrasound examination of the gastric antrum allows a reliable assessment of gastric contents and volume and might help contribute to improve perioperative care in the emergency setting.

Methods
Gastric ultrasound examinations were performed preoperatively and postoperatively on forty-one patients undergoing emergency abdominal surgery. Gastric cross-sectional area (CSA) was measured, in order to estimate the gastric volume. The data obtained were used to evaluate a possible relationship between delayed gastric emptying and postoperative adverse event.

Results
Gastric antrum detection rate varied from 31.8% in open up to 78.9% in laparoscopic surgeries (p = 0.003). Six patients experienced adverse outcomes, had an antiemetic therapy administered and/or a nasogastric tube inserted. Mean CSA was significantly higher in this group (12.95 cm2 vs 6.12 cm2; p = 0.040).

Conclusions
Sensitivity of gastric ultrasound varies depending on surgical technique. A dilated gastric antrum is significantly related to postoperative adverse outcomes and a careful ultrasound follow-up might help tailor postoperative nutrition and antiemetic therapy. In patients who experienced adverse events, antral CSA showed an average increase of more than 50% over a period of 72 h after surgery. A relative measure could be used to predict the risk of postoperative ileus. Overall, gastric ultrasound seems to be a promising diagnostic tool and a useful way to integrate ERAS® protocol in emergency abdominal surgery.
Development and validation of a structured survey questionnaire on knowledge, attitude, preventive practice, and treatment-seeking behaviour regarding dengue among the resident population of Sabah, Malaysia: an exploratory factor analysis
Authors: Guad Rhanye Mac , Mangantig Ernest , Low Wah Yun , Taylor-Robinson Andrew W. , Azzani Meram , Sekaran Shamala Devi , Sim Maw Shin , Azizan Nornazirah 
Published: August 2021

Abstract
Background
Several studies have reported a significant association of knowledge, attitude and preventive practice (KAP) regarding dengue infection among community’s resident in endemic areas. In this study we aimed to assess and develop a reliable and valid KAP survey on the subject of dengue that is suitable for the resident population of Sabah, Malaysia.

Methods
A community-based cross-sectional study was conducted from October 2019 to February 2020 involving 468 respondents. Information on the socio-demographic characteristics of the participants (six items), their KAP (44, 15 and 18 items on knowledge, attitude and practice, respectively) and treatment-seeking behaviour (five items) towards dengue was collected using a structured questionnaire. Data analysis was performed using SPSS and R software in the R Studio environment. The knowledge section was analysed by two-parameter logistic item response theory (2-PL IRT) using ltm package. The construct validity and reliability of items for sections on attitude, practice and treatment-seeking behaviour were analysed using psy package.

Results
For the knowledge section, only 70.5% (31/44) of items were within or close to the parameter acceptable range of −3 to + 3 of difficulty. In terms of discrimination, 65.9% (29/44) of items were within or close to the acceptable range of 0.35 to 2.5, and 24 items (54.5%) failed to fit the 2-PL IRT model (P < 0.05) after assessing by goodness-of-fit analysis. Only eight items were reliable and retained in the attitude section with a Kaiser–Meyer–Olkin (KMO) test value of > 0.7, while based on the communalities, 11 items in the attitude section were excluded due to very low h2, factor loading values and low correlation with the total (< 0.5). The practice section was found suitable for factor analysis because the KMO value was > 0.7. The communalities of the practice section showed that seven items had low h2 values (< 0.3), which were therefore excluded from further analysis, and only 11 items were retained.

Conclusions
The KAP items retained in the final version of the survey were reliable and valid to be use as a questionnaire reference when conducting future similar studies among the population of Sabah.
Negative effects of iodine-based contrast agent on renal function in patients with moderate reduced renal function hospitalized for COVID-19
Authors: Kistner Anna , Tamm Chen , Svensson Ann Mari , Beckman Mats O. , Strand Fredrik , Sköld Magnus , Nyrén Sven 
Published: August 2021

Abstract
Background
Kidney disease and renal failure are associated with hospital deaths in patients with COVID − 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID − 19 patients.

Methods
Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4–10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 μmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4–10 days after contrast-enhanced CT.

Results
Median P-creatinine at 24–48 h and days 4–10 post-CT in patients with eGFR> 60 and eGFR≥30–60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4–10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30–60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30–60 and 30-day mortality were associated with CK-AKI both at 48 h and 4–10 days after contrast-enhanced CT.

Conclusion
Patients with COVID − 19 and eGFR≥30–60 had a high frequency of CK-AKI at 48 h and at 4–10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30–60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.
Postoperative results of ventilation tube insertion: a retrospective multicenter study for suggestion of grading system of otitis media with effusion
Authors: Song Chan Il , Kang Byung Chul , Shin Chol Ho , An Yun Suk , Kim Tae Su , Lim Hyun Woo , Shim Hyun Joon , Yoo Myung Hoon , Ahn Joong Ho 
Published: August 2021

Abstract
Background
In otitis media with effusion (OME), it is important to know when to surgically intervene and when careful monitoring is more appropriate. This study aimed to visualize and classify the clinical manifestations of OME and the correlation between the new grading system and postoperative results after ventilation tube insertion (VTI).

Methods
We classified the collective 1,012 ears from 506 patients into six groups: grade 0 (no effusion), grade I (scant effusion, but abnormal), grade II (effusion less than half of the tympanic cavity), grade III (effusion over half of the tympanic cavity, with air bubbles), grade IV (complete effusion), and grade V (retracted tympanic membrane or hemotympanum without air bubbles).

Results
The mean age at VTI was 5.2 (±2.9) years and mean duration between diagnosis and operation was 4.1 (±1.8) months. Between the grades, the nature of the middle ear effusion was also significantly different (p < 0.001). The duration of ventilation tube retention after VTI was significantly different when compared between two groups: grade I-IV and grade V (p = 0.019). Our results showed that the recurrence rate, as well as rate of revision VTI, increased as the grade increased (p < 0.001).

Conclusions
The new grading system of OME using endoscopic otoscope evaluation had a significant correlation with the age at VTI, the nature of middle ear effusion, the recurrence rate of OME, and the rate of revision VTI.
Correlates of transitions from alcohol use to disorder diagnosed by DSM-5 in China
Authors: Zhang Tingting , Liu Zhaorui , Li Guohua , Huang Yueqin , Li Yanxiang , Geng Hongchun , Cheng Hui G. 
Published: August 2021

Abstract
Background
This study aimed to describe the prevalence and lifetime criteria profiles of DSM-5 alcohol use disorder (AUD) and the transitions from alcohol use to disorder in Chifeng, China.

Methods
Face-to-face interviews were conducted using Composite International Diagnostic Interview-3.0 (CIDI-3.0) among 4528 respondents in Chifeng.

Results
The weighted lifetime and 12-month prevalence of DSM-5 AUD were 3.03 and 1.05%, respectively. Mild lifetime AUD was the most prevalent severity level (69.53%). The two most common criteria were “failure to quit/cutdown” and “drinking more or for longer than intended.” Lifetime prevalence was 65.59% for alcohol use, and 22.97% for regular drinking. Male and domestic violence were risk factors for the transition from alcohol use to regular drinking or AUD and from regular drinking to AUD. Younger age was risk factor for the transition to AUD from alcohol use or regular drinking. Poverty (OR = 2.49) was risk factor for the transition from alcohol use to regular drinking. The earlier drinkers were more likely to develop to regular drinking (OR = 2.11).

Conclusion
AUD prevalence in Chifeng was not as high as that in Western countries. The study revealed that multiple risk factors might contribute to the transition across different stages of alcohol use. Further research should explore the underlying mechanisms.