bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics, treatment and efficacy of calcaneal osteomyelitis: a systematic review with synthesis analysis of 1118 reported cases
Authors: Jiang Nan , Chen Peng , Liu Guan-Qiao , Huang Mou-Zhang , Deng Ming-Ye , Song Ming-Rui , Zhu Run-Jiu , Zhong Hong-Fa , Xiang Da-Yong , Yu Bin 
Published: June 2024

Background:
Calcaneal osteomyelitis (CO) still poses great challenges to orthopedic surgeons due to the unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases.

Materials and methods:
The authors searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients published between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis.

Results:
Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcers (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately.

Conclusions:
CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.
Functional Outcomes After Transanal Total Mesorectal Excision (taTME) for Rectal Cancer
Authors: Donovan Katherine F. , Lee Katherine C. , Ricardo Alison , Berger Natalie , Bonaccorso Antoinette , Alavi Karim , Zaghiyan Karen , Pigazzi Alessio , Sands Dana , DeBeche-Adams Teresa , Chadi Sami A. , McLemore Elisabeth C. , Marks John H. , Maykel Justin A. , Shawki Sherief F. , Steele Scott R. , Albert Matthew , Whiteford Mark H. , Cheng Fu-Yuan , Wexner Steven D. , Sylla Patricia 
Published: June 2024

Objective:
To investigate fecal incontinence and defecatory, urinary, and sexual functional outcomes after transanal total mesorectal excision (taTME).

Background:
Proctectomy for rectal cancer may result in alterations in defecatory, urinary, and sexual function that persist beyond 12 months. The recent multicenter phase II taTME trial demonstrated the safety of taTME in patients with stage I to III tumors.

Methods:
Prospectively registered self-reported questionnaires were collected from 100 taTME patients. Fecal continence [Fecal Incontinence Quality of Life (FIQL), Wexner], defecatory function [Colorectal Functional Outcome (COREFO)], urinary function (International Prostate Symptom Score), and sexual function (Female Sexual Function Index-female, International Index of Erectile Function-male) were assessed preoperatively (PQ), 3 to 4 months postileostomy closure (FQ1), and 12 to 18 months post-taTME [postoperative questionnaire 2 (FQ2)].

Results:
Among 83 patients who responded at all 3 time points, FIQL, Wexner, and COREFO significantly worsened postileostomy closure. Between FQ1 and FQ2, FIQL lifestyle and coping, Wexner, and COREFO incontinence, social impact, frequency, and need for medication significantly improved, while FIQL depression and embarrassment did not change. International Prostate Symptom Score did not change relative to preoperative scores. For females, Female Sexual Function Index declined for desire, orgasm, and satisfaction between PQ and FQ1, and did not improve between FQ1 and FQ2. In males, International Index of Erectile Function declined with no change between FQ1 and FQ2.

Conclusions:
Although taTME resulted in initial decline in defecatory function and fecal continence, most functional domains improved by 12 months after ileostomy closure, without returning to preoperative status. Urinary function was preserved while sexual function declined without improvement by 18 months post-taTME. Our results address patient expectations and inform shared decision-making regarding taTME.
mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain
Authors: Jensen Kathrine Louise , Chistensen Nikolaj Riis , Goddard Carolyn Marie , Jager Sara Elgaard , Kanneworff Ida Buur , Jakobsen Alexander , Noes-Holt Gith , Jiménez-Fernández Lucía , Peck Emily G. , Sivertsen Line , Baro Raquel Comaposada , Houser Grace Anne , Mayer Felix Paul , Diaz-delCastillo Marta , Topp Marie Løth , Hopkins Chelsea , Thomsen Cecilie Dubgaard , Soltan Ahmed Barakat Ibrahim , Tidemand Frederik Grønbæk , Arleth Lise , Heegaard Anne-Marie , Sørensen Andreas Toft , Madsen Kenneth Lindegaard 
Published: June 2024

ABSTRACTChronic pain is a complex, debilitating, and escalating health problem worldwide, impacting one in five adults. Current treatment is compromised by dose-limiting side effects including high abuse liability, loss of ability to function socially and professionally, fatigue, drowsiness, and apathy. PICK1 has emerged as a promising target for the treatment of chronic pain conditions. Here, we develop and characterize a cell-permeable fatty acid conjugated bivalent peptide inhibitor of PICK1 and assess its effects on acute and chronic pain. The myristoylated myr-NPEG4-(HWLKV)2, (mPD5), self-assembles into core-shell micelles that provide favourable pharmacodynamic properties and relieves ongoing and evoked mechanical hypersensitivity, thermal hypersensitivity as well as anxio-depressive symptoms in mouse models of neuropathic and inflammatory pain following subcutaneous administration. No overt no side effects were associated with mPD5 administration, and it has no effect on acute nociception. Finally, neuropathic pain is relieved far into the chronic phase (18 weeks post SNI surgery) and while the effect of a single injection ceases after a few hours, repeated administration provides pain relief lasting up to 20 hours after the last injection.
The Hippo/YAP Pathway Mediates the De-differentiation of Corneal Epithelial Cells into Functional Limbal Epithelial Stem CellsIn Vivo
Authors: Li Yijian , Ge Lingling , Ren Bangqi , Zhang Xue , Yin Zhiyuan , Liu Hongling , Yang Yuli , Liu Yong , Xu Haiwei 
Published: June 2024

AbstractRegeneration after tissues injury is often associated with cell fate plasticity, which restores damaged or lost cells. The de-differentiation of corneal epithelial cells (CECs) into functional stem cells after the ablation of innate stem cells, known as limbal epithelial stem cells (LESCs), remains controversial. In this study, we showed the functional maintenance of corneal epithelium after the ablation of innate stem cells, and the regeneration of functional LESCs, which maintained corneal transparency, prevented corneal conjunctivalization and participated in the wound healing. Subsequent intravital lineage tracing revealed that CECs could de-differentiate into active or quiescent LESCs, which functioned as well as their innate counterparts. Furthermore, the de-differentiation of CECs required an intact limbal niche, and the outcome of the competition between conjunctival and corneal epithelium for the limbal niche determined whether the de-differentiation would occur or not. Mechanically, the suppression of YAP signal promoted the de-differentiation of CECs after the ablation of innate stem cells, while the persistent activation of YAP prevented the de-differentiation of CECs after an additional alkali burn to the limbal stroma. These results will pave the way for an alternative approach to treat limbal stem cell deficiency (LSCD) by modulating the de-differentiation of CECsin vivo.
More is better: A simple antibody-based strategy for recovering all major mouse brain cell types from multiplexed single-cell RNAseq samples
Authors: Pratesi Federico , Hamilton Laura K. , Avila Lopez Jessica , Aumont Anne , Avino Mariano , Singh Nishita , Arefiev Ihor , Brunet Marie A. , Fernandes Karl J. L. 
Published: June 2024

ABSTRACTSingle-cell RNA sequencing (scRNAseq) is a powerful yet costly technique for studying cellular diversity within the complexity of organs and tissues. Here, we sought to establish an effective multiplexing strategy for the adult mouse brain that could allow multiple experimental groups to be pooled into a single sample for sequencing, reducing costs, increasing data yield, and eliminating batch effects. We first describe an optimized cold temperature single-cell dissociation protocol that permits isolation of a high yield and viability of brain cells from the adult mouse. Cells isolated using this protocol were then screened by flow cytometry using a panel of antibodies, allowing identification of a single antibody, anti-Thy1.2, that can tag the vast majority of isolated mouse brain cells. We then used this primary antibody against a “universal” neural target, together with secondary antibodies carrying sample-specific oligonucleotides and the BD Rhapsody single-cell system and show that multiple adult mouse brain samples can be pooled into a single multiplexed run for scRNAseq. Bioinformatic analyses enable efficient demultiplexing of the sequenced pooled brain sample, with high tagging efficiency and precise annotation and clustering of brain cell populations. The efficiency and flexibility of the cell dissociation protocol and the two-step multiplexing strategy simplifies experimental design, optimizes reagent usage, eliminates sequencing batch effects and reduces overall experimental costs.
Association between lactate to albumin ratio and acute kidney injury in patients with sepsis: a retrospective cohort study from MIMIC-IV database
Authors: Wang Yaotang , Yu Haixia 
Published: June 2024

AbstractBackgroundThe mortality rate of sepsis-associated acute kidney injury (S-AKI) is high, yet there is a lack of authoritative prognostic criteria for its outcome. The lactate-to-albumin ratio (LAR) has been associated with mortality in conditions such as sepsis, heart failure, and respiratory failure. However, there is limited research on the relationship between LAR and S-AKI. This study aimed to investigate the association between LAR and the mortality rate of S-AKI.MethodsIn our study, we performed a retrospective cohort analysis using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Our primary focus was on determining the occurrence of 30-day, 60-day, and in-hospital mortality as the primary outcomes. To validate the association between LAR and these outcomes, we employed multivariable logistic Cox regression models to calculate hazard ratios.ResultsThis study included a total of 4793 participants, with a mean age of 63.3 years and a median LAR (log2) of -0.90. After accounting for confounding variables, it was found that patients in the highest LAR (log2) quartile had a higher risk of mortality compared to those in the lowest LAR (log2) quartile. The adjusted hazard ratios for mortality were 1.44 (95% confidence interval [CI]: 1.36∼1.53), 1.38 (95% CI: 1.32∼1.46), and 1.47 (95% CI: 1.39∼1.56) for the highest LAR (log2) quartile, respectively. Moreover, the adjusted hazard ratios for mortality at 30-day, 90-day, and in-hospital intervals were 1.28 (95% CI: 1.23∼1.33), 1.26 (95% CI: 1.21∼1.31), and 1.27 (95% CI: 1.22∼1.32) for each 1 unit increase in LAR, respectively.ConclusionThis study indicates that in septic AKI patients, a higher LAR is associated with an increased risk of all-cause mortality within 30-day, 90-day and in-hospital mortality. This suggests that LAR may serve as an independent risk factor for adverse outcomes in septic AKI patients.
Genetic encoding and expression of RNA origami cytoskeletons in synthetic cells
Authors: Tran Mai P. , Chakraborty Taniya , Poppleton Erik , Monari Luca , Giessler Franziska , Göpfrich Kerstin 
Published: June 2024

AbstractThe central dogma at the core of molecular biology states that information flows from DNA to RNA and then to protein. Our research seeks to introduce a conceptually novel approach towards synthetic life by leveraging RNA origami, as an alternative to proteins, requiring only a single copying step between genetic information and function. Here, we report the genetic encoding and expression of an RNA origami cytoskeleton-mimic within giant unilamellar lipid vesicles (GUVs). We design the first RNA origami tiles which fold co-transcriptionally from a DNA template and self-assemble into higher-order 3D RNA origami nanotubes at constant 37◦C in GUVs, where they reach several micrometers in length. Unlike pre-formed and encapsulated DNA cytoskeletons, these GUVs produce their own molecular hardware in an out-of-equilibrium process fuelled by nucleotide feeding. To establish genotype-phenotype correlations, we investigate how sequence mutations govern the contour and persistence length of the RNA origami nanotubes with experiments and coarse-grained molecular-dynamics simulations, realizing a phenotypic transition to closed rings. Finally, we achieve RNA origami cortex formation and GUV deformation without chemical functionalization by introducing RNA aptamers into the tile design.Altogether, this work pioneers the expression of RNA origami-based hardware in vesicles as a new approach towards active, evolvable and RNA-based synthetic cells.
LDL exposure disrupts mitochondrial function and dynamics in a hippocampal neuronal cell line
Authors: Farias Hémelin Resende , Ramos Jessica Marques Obelar , Griesang Caroline , Santos Lucas , Ramires Junior Osmar Vieira , de Souza Debora Guerini , Ferreira Fernanda Silva , Somacal Sabrina , Martins Leo Anderson Meira , de Souza Diogo Onofre Gomes , Moreira José Cláudio Fonseca , de Souza Wyse Ângela Terezinha , Guma Fátima Theresinha Costa Rodrigues , de Oliveira Jade 
Published: June 2024

ABSTRACTHypercholesterolemia has been associated with cognitive dysfunction and neurodegenerative disease. Moreover, this metabolic condition disrupts the blood-brain barrier, allowing Low-Density Lipoprotein (LDL) to enter the Central Nervous System. Thus, we investigated the effects of LDL exposure on mitochondrial function in a mouse hippocampal neuronal cell line (HT-22). HT-22 cells were exposed to human LDL (50 and 300 μg/mL) for 24 hours. After this, intracellular lipid droplet (LD) content, cell viability, cell death, and mitochondrial parameters were performed. We found that the higher LDL concentration LDL increases LD content compared to control. Both concentrations increased the number of Annexin V-positive cells, indicating apoptosis. Moreover, in mitochondrial parameters, the exposure of LDL on hippocampal neuronal cell line leads to a decrease in mitochondrial complexes I and II in both concentrations tested and a reduction in Mitotracker™ Red fluorescence and Mitotracker™ Red and Mitotracker™ Green ratio in the higher concentration, indicating dysfunction in the mitochondria. The LDL incubation induces mitochondrial superoxide production and a decrease in superoxide dismutase activity in the lower concentration in HT-22 cells. Finally, hippocampal neuronal cell line exposed to LDL exhibit an increase in the expression of genes associated with mitochondrial fusion (OPA1 and Mitofusin 2) in the lower concentration. In conclusion, our findings suggest that LDL exposure induces mitochondrial dysfunction and modulation in mitochondrial dynamics in the hippocampal neuronal cells.
Molecular insights into the interaction between a disordered protein and a folded RNA
Authors: Mitra Rishav , Usher Emery T. , Dedeoğlu Selin , Crotteau Matthew J. , Fraser Olivia A. , Yennawar Neela H. , Gadkari Varun V. , Ruotolo Brandon T. , Holehouse Alex S. , Salmon Loïc , Showalter Scott A. , Bardwell James C. A. 
Published: June 2024

ABSTRACTIntrinsically disordered protein regions (IDRs) are well-established as contributors to intermolecular interactions and the formation of biomolecular condensates. In particular, RNA-binding proteins (RBPs) often harbor IDRs in addition to folded RNA-binding domains that contribute to RBP function. To understand the dynamic interactions of an IDR-RNA complex, we characterized the RNA-binding features of a small (68 residues), positively charged IDR-containing protein, SERF. At high concentrations, SERF and RNA undergo charge-driven associative phase separation to form a protein- and RNA-rich dense phase. A key advantage of this model system is that this threshold for demixing is sufficiently high that we could use solution-state biophysical methods to interrogate the stoichiometric complexes of SERF with RNA in the one-phase regime. Herein, we describe our comprehensive characterization of SERF alone and in complex with a small fragment of the HIV-1 TAR RNA (TAR) with complementary biophysical methods and molecular simulations. We find that this binding event is not accompanied by the acquisition of structure by either molecule; however, we see evidence for a modest global compaction of the SERF ensemble when bound to RNA. This behavior likely reflects attenuated charge repulsion within SERF via binding to the polyanionic RNA and provides a rationale for the higher-order assembly of SERF in the context of RNA. We envision that the SERF-RNA system will lower the barrier to accessing the details that support IDR-RNA interactions and likewise deepen our understanding of the role of IDR-RNA contacts in complex formation and liquid-liquid phase separation.SIGNIFICANCESubcellular organization through the formation of biomolecular condensates has emerged as an important contributor to myriad cellular functions, with implications in homeostasis, stress response, and disease. To understand the general and specific principles that support condensate formation, we must interrogate the interactions and assembly of their constituent biomolecules. To this end, this study introduces a simple model system comprised of a small, disordered protein and small RNA that undergo charge-driven, associative phase separation. In addition to extensive biophysical characterization of these molecules and their complex, we also generate new insights into mode of interaction and assembly between an unstructured protein and a structured RNA.
Isoform and pathway-specific regulation of post-transcriptional RNA processing in human cells
Authors: Bedi Karan , Magnuson Brian , Narayanan Ishwarya Venkata , McShane Ariel , Ashaka Mario , Paulsen Michelle T. , Wilson Thomas E. , Ljungman Mats 
Published: June 2024

ABSTRACTSteady-state levels of RNA transcripts are controlled by their rates of synthesis and degradation. Here we used nascent RNA Bru-seq and BruChase-seq to profile RNA dynamics across 16 human cell lines as part of ENCODE4 Deeply Profiled Cell Lines collection. We show that RNA turnover dynamics differ widely between transcripts of different genes and between different classes of RNA. Gene set enrichment analysis (GSEA) revealed that transcripts encoding proteins belonging to the same pathway often show similar turnover dynamics. Furthermore, transcript isoforms show distinct dynamics suggesting that RNA turnover is important in regulating mRNA isoform choice. Finally, splicing across newly made transcripts appears to be cooperative with either all or none type splicing. These data sets generated as part of ENCODE4 illustrate the intricate and coordinated regulation of RNA dynamics in controlling gene expression to allow for the precise coordination of cellular functions.
Improving Adherence to electronic Patient-Reported Outcomes:Study Protocol for a Systematic Literature Review and subsequent qualitative Interviews
Authors: Mukowski-Kickhöfel Rebecca , Otto Lisa , Rogge Alizé 
Published: June 2024

AbstractBackgroundElectronic patient-reported outcomes (ePROs) are frequently used to include the patients’ perspective in clinical trials and routine clinical care. In contrast to data collected in clinical trials, PRO response rates tend to decrease drastically overtime in routine clinical care, leading to missing data and questionable validity of results reported. This study aims to investigate factors influencing patient adherence to digitally collected PROs.MethodThe study comprises of three steps: (1) a systematic literature review (SLR) focusing on factors increasing PRO response rates, (2) focus group interviews with patients to develop criteria on how to increase response rates for real-world evidence (RWE), and subsequently, (3) an anonymous online survey to evaluate developed criteria. The SLR will follow the PRISMA guidelines. The inclusion criteria for the review encompass studies focusing exclusively on patients or people recruited via medical personnel. The literature review will include studies from various settings, encompassing publications in German or English language published within the past 10 years (2014-2024). Participants for the focus group interviews (n = 6-8/group) will be recruited via patient advisory boards or groups/organisations. The findings of the SLR and the focus group form the basis for the anonymous online survey to include more patients.OutlookThe results of the study can be incorporated into the development and implementation of digital collection methods for PROs, with the aim of improving adherence to PROs and thus robustness of RWE data.
Corporate board characteristics and CSR budget of selected Bangladeshi banks: moderating role of corporate reputation
Authors: Hosain Md Sajjad 
Published: June 2024

PurposeThis study explores the relationships between corporate board characteristics (CBCs) and corporate social responsibility budget (CSRB) of selected Bangladeshi banks. CSRB was regarded as the sole dependent variable. In contrast, CBCs was separated into three independent constructs: board members' age (BMA), board members’ educational level (BMEL) and the number of board meetings per year (NBMY). A single moderator, corporate reputation (CR), was used to assess the moderating impact on the direct relationships.Design/methodology/approachAnnual reports from 2017 to 2021 (5 years) of 25 selectively listed Bangladeshi banks were used as study samples. Further, the researcher conducted informal interviews with 251 board members of those selected banks using a semi-structured questionnaire. The study used “multiple regression analysis” to evaluate the moderating effects on the three direct relationships and “Pearson's correlation coefficient” to assess the immediate impacts.FindingsAfter analysis, the results revealed that all the three independent components, BMA, BMEL and NBMY, have substantial positive relationships with the dependent variable, CSRB. Moreover, it was identified that CR can moderate (strengthen) all the three direct relationships. Originality/valueCorporate governance (CG) and CSR are two hot topics both in academia and practice. This study highlighted the corporate board characteristics and CSR budget, two new dimensions of CG literature that are required to be paid more attention to. The researcher expects this study to enhance the literature focused on these newer dimensions of CG that might benefit both academics and practitioners.